View source for Wolbachia

{{Short description|Genus of bacteria in the Alphaproteobacteria class}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Automatic taxobox
| image = Wolbachia.png
| image_caption = Transmission electron micrograph of ''Wolbachia'' within an insect cell<br />Credit:[[Public Library of Science]] / Scott O'Neill
| taxon = Wolbachia
| authority = Hertig 1936 (Approved Lists 1980)
| subdivision_ranks = Species
| subdivision =
* "''Candidatus Wolbachia bourtzisii''" <small>Ramirez-Puebla et al. 2015</small>
* "''Candidatus Wolbachia brugii''" <small>Ramirez-Puebla et al. 2015</small>
* "''Candidatus Wolbachia collembolicola''" <small>Ramirez-Puebla et al. 2015</small>
* "''Candidatus Wolbachia ivorensis''" <small>Ehounoud et al. 2016</small>
* ''[[Wolbachia melophagi]]'' <small>(Nöller 1917) Philip 1956 (Approved Lists 1980)</small>
* "''Candidatus Wolbachia multihospitum''" <small>Ramirez-Puebla et al. 2015</small>
* "''Candidatus Wolbachia onchocercicola''" <small>Ramirez-Puebla et al. 2015</small>
<!-- Wolbachia persica was reclassified as Francisella persica. -->
* ''[[Wolbachia pipientis]]'' <small>Hertig 1936 (Approved Lists 1980)</small>
}}

'''''Wolbachia''''' is a [[genus]] of [[gram-negative bacteria]] infecting many species of [[arthropod|arthropods]] and [[filarial nematodes]].<ref>{{cite journal |title=Genome Sequence of the Intracellular Bacterium Wolbachia |journal=PLOS Biology |date=March 2004|volume=2 |issue=3 |pages=e76 |doi=10.1371/journal.pbio.0020076 |pmc=368170 |doi-access=free}}</ref><ref name="Taylor 2018">{{cite journal | vauthors = Taylor MJ, Bordenstein SR, Slatko B | title = Microbe Profile: Wolbachia: a sex selector, a viral protector and a target to treat filarial nematodes | journal = Microbiology | volume = 164 | issue = 11 | pages = 1345–1347 | date = November 2018 | pmid = 30311871 | pmc = 7008210 | doi = 10.1099/mic.0.000724 | doi-access = free }}</ref> The symbioitic relationship ranges from parasitism to obligate mutualism. It is one of the most common [[parasitic]] [[microbe]]s of arthropods, and is possibly the most widespread [[reproductive]] parasite bacterium in the [[biosphere]].<ref>{{cite journal | vauthors = Duron O, Bouchon D, Boutin S, Bellamy L, Zhou L, Engelstädter J, Hurst GD | title = The diversity of reproductive parasites among arthropods: Wolbachia do not walk alone | journal = BMC Biology | volume = 6 | issue = 1 | pages = 27 | date = June 2008 | pmid = 18577218 | pmc = 2492848 | doi = 10.1186/1741-7007-6-27 | doi-access = free }}</ref> Its interactions with hosts are complex and highly diverse across different host species. Some host species cannot reproduce, or even survive, without ''Wolbachia'' [[Colonisation (biology)|colonisation]]. One study concluded that more than 16% of [[neotropical]] insect species carry bacteria of this genus,<ref>{{Cite journal | vauthors = Werren JH, Windsor D, Guo LR |year=1995 |title=Distribution of ''Wolbachia'' among neotropical arthropods |journal=[[Proceedings of the Royal Society B]] |volume=262 |issue=1364 |pages=197–204|bibcode=1995RSPSB.262..197W | doi=10.1098/rspb.1995.0196 |s2cid=86540721 }}</ref> and as many as 25 to 70% of all insect species are estimated to be potential hosts.<ref>{{Cite book |chapter=The Discovery of Wolbachia in Arthropods and Nematodes – A Historical Perspective | vauthors = Kozek WJ, Rao RU | title = Wolbachia: A Bug's Life in another Bug |year=2007 |volume=5 |issue=''Wolbachia'': A Bug's Life in another Bug |pages=1–14 |doi=10.1159/000104228 |series=Issues in Infectious Diseases |isbn=978-3-8055-8180-6}}</ref>

{{Toclimit}}

==History==
The first organism classified as ''Wolbachia'' was discovered in 1924 by Marshall Hertig and [[Simeon Burt Wolbach]] in the [[Culex pipiens|common house mosquito]]. They described it as "a somewhat [[Pleomorphism (microbiology)|pleomorphic]], [[Bacillus (shape)|rodlike]], [[Gram stain|Gram-negative]], intracellular organism [that] apparently infects only the [[ovary|ovaries]] and [[testicle|testes]]".<ref>{{cite journal | vauthors = Hertig M, Wolbach SB | title = Studies on Rickettsia-Like Micro-Organisms in Insects | journal = The Journal of Medical Research | volume = 44 | issue = 3 | pages = 329–374.7 | date = March 1924 | pmid = 19972605 | pmc = 2041761 }}</ref> Hertig formally described the species in 1936, and proposed both the [[genus|generic]] and [[species|specific]] names: ''Wolbachia pipientis''.<ref>{{cite journal | vauthors = Hertig M |title=The Rickettsia, Wolbachia pipientis (gen. et sp. n.) |journal=Parasitology |date=October 1936 |volume=28 |issue=4 |pages=453–486|doi=10.1017/S0031182000022666 |s2cid=85793361 }}</ref> 

Research on ''Wolbachia'' intensified after 1971, when Janice Yen and A. Ralph Barr of [[University of California, Los Angeles|UCLA]] discovered that ''Culex'' mosquito eggs were killed by a [[cytoplasmic incompatibility]] when the sperm of ''Wolbachia''-infected males fertilized infection-free eggs.<ref>{{cite journal | vauthors = Yen JH, Barr AR | title = New hypothesis of the cause of cytoplasmic incompatibility in Culex pipiens L | journal = Nature | volume = 232 | issue = 5313 | pages = 657–658 | date = August 1971 | pmid = 4937405 | doi = 10.1038/232657a0 | s2cid = 4146003 | bibcode = 1971Natur.232..657Y }}</ref><ref>{{cite book |title=Insect Symbiosis | veditors = Bourtzis K, Miller TA |isbn=978-0-8493-4194-6 |chapter=14: Insect pest control using Wolbachia and/or radiation |chapter-url=https://books.google.com/books?id=Y9_HAm28SoYC&pg=PA230 |page=230 |year=2003 | last1 = Bourtzis | first1 = Kostas | last2 = Miller | first2 = Thomas A. | publisher = Taylor & Francis }}</ref> 

Since, a large number of bacteria with close phylogenetic affinity to the originally detected ''W. pipientis'' have been discovered in a variety of hosts spanning over the [[Arthropod|Arthropoda]] and [[Nematode|Nematoda]] phyla. The taxonomic classification of the various discovered groups remains a subject of debate, with no consensus on whether these groups of ''Wolbachia pipientis''-like organisms should be categorized as the same or different species. Therefore, the strains are collectively referred to as ''Wolbachia'', with the various groups of phylogenetically closely related strains designated as supergroups rather than distinct species. In general, each supergroup corresponds to a specific host or group of hosts<ref>{{Cite journal |last=Lo |first=N. |last2=Paraskevopoulos |first2=C. |last3=Bourtzis |first3=K. |last4=O'Neill |first4=S. L. |last5=Werren |first5=J. H. |last6=Bordenstein |first6=S. R. |last7=Bandi |first7=C. |date=2007 |title=Taxonomic status of the intracellular bacterium Wolbachia pipientis |url=https://www.microbiologyresearch.org/content/journal/ijsem/10.1099/ijs.0.64515-0 |journal=International Journal of Systematic and Evolutionary Microbiology |volume=57 |issue=3 |pages=654–657 |doi=10.1099/ijs.0.64515-0 |issn=1466-5034}}</ref>. The genus ''Wolbachia'' is of considerable interest today due to its ubiquitous distribution, its many different evolutionary interactions, and its potential use as a [[Biological pest control|biocontrol agent]]. 

Phylogenetic studies have showed that the closest relatives to ''Wolbachia'' are the genera ''[[Francisella]]''<ref>{{cite journal |vauthors=Forsman M, Sandström G, Sjöstedt A |date=January 1994 |title=Analysis of 16S ribosomal DNA sequences of Francisella strains and utilization for determination of the phylogeny of the genus and for identification of strains by PCR |journal=International Journal of Systematic Bacteriology |volume=44 |issue=1 |pages=38–46 |doi=10.1099/00207713-44-1-38 |pmid=8123561 |doi-access=free}}</ref><ref>{{cite journal |vauthors=Noda H, Munderloh UG, Kurtti TJ |date=October 1997 |title=Endosymbionts of ticks and their relationship to Wolbachia spp. and tick-borne pathogens of humans and animals |journal=Applied and Environmental Microbiology |volume=63 |issue=10 |pages=3926–3932 |bibcode=1997ApEnM..63.3926N |doi=10.1128/AEM.63.10.3926-3932.1997 |pmc=168704 |pmid=9327557}}</ref><ref>{{cite journal |vauthors=Niebylski ML, Peacock MG, Fischer ER, Porcella SF, Schwan TG |date=October 1997 |title=Characterization of an endosymbiont infecting wood ticks, Dermacentor andersoni, as a member of the genus Francisella |journal=Applied and Environmental Microbiology |volume=63 |issue=10 |pages=3933–3940 |bibcode=1997ApEnM..63.3933N |doi=10.1128/AEM.63.10.3933-3940.1997 |pmc=168705 |pmid=9327558}}</ref><ref>{{cite journal |vauthors=Larson MA, Nalbantoglu U, Sayood K, Zentz EB, Cer RZ, Iwen PC, Francesconi SC, Bishop-Lilly KA, Mokashi VP, Sjöstedt A, Hinrichs SH |date=March 2016 |title=Reclassification of Wolbachia persica as Francisella persica comb. nov. and emended description of the family Francisellaceae |journal=International Journal of Systematic and Evolutionary Microbiology |volume=66 |issue=3 |pages=1200–1205 |doi=10.1099/ijsem.0.000855 |pmid=26747442 |doi-access=free}}</ref> and ''[[Bartonella]]''<ref>{{cite journal | vauthors = Dumler JS, Barbet AF, Bekker CP, Dasch GA, Palmer GH, Ray SC, Rikihisa Y, Rurangirwa FR | title = Reorganization of genera in the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales: unification of some species of Ehrlichia with Anaplasma, Cowdria with Ehrlichia and Ehrlichia with Neorickettsia, descriptions of six new species combinations and designation of Ehrlichia equi and 'HGE agent' as subjective synonyms of Ehrlichia phagocytophila | journal = International Journal of Systematic and Evolutionary Microbiology | volume = 51 | issue = Pt 6 | pages = 2145–2165 | date = November 2001 | pmid = 11760958 | doi = 10.1099/00207713-51-6-2145 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lo N, Paraskevopoulos C, Bourtzis K, O'Neill SL, Werren JH, Bordenstein SR, Bandi C | title = Taxonomic status of the intracellular bacterium Wolbachia pipientis | journal = International Journal of Systematic and Evolutionary Microbiology | volume = 57 | issue = Pt 3 | pages = 654–657 | date = March 2007 | pmid = 17329802 | doi = 10.1099/ijs.0.64515-0 | doi-access = free }}</ref><ref name="Maggi">{{cite journal | vauthors = Maggi RG, Kosoy M, Mintzer M, Breitschwerdt EB | title = Isolation of Candidatus Bartonella melophagi from human blood | journal = Emerging Infectious Diseases | volume = 15 | issue = 1 | pages = 66–68 | date = January 2009 | pmid = 19116054 | pmc = 2660712 | doi = 10.3201/eid1501.081080 | doi-access = free }}</ref> . Unlike ''Wolbachia'', which needs a host cell to multiply, relatives beloning to these genera can be cultured on [[agar plate]]s.<ref>{{cite journal | vauthors = Öhrman C, Sahl JW, Sjödin A, Uneklint I, Ballard R, Karlsson L, McDonough RF, Sundell D, Soria K, Bäckman S, Chase K, Brindefalk B, Sozhamannan S, Vallesi A, Hägglund E, Ramirez-Paredes JG, Thelaus J, Colquhoun D, Myrtennäs K, Birdsell D, Johansson A, Wagner DM, Forsman M | title = Reorganized Genomic Taxonomy of ''Francisellaceae'' Enables Design of Robust Environmental PCR Assays for Detection of ''Francisella tularensis'' | journal = Microorganisms | volume = 9 | issue = 1 | page = 146 | date = January 2021 | pmid = 33440900 | pmc = 7826819 | doi = 10.3390/microorganisms9010146 | doi-access = free }}</ref><ref name="Maggi" />

==Method of sexual differentiation in hosts==
''Wolbachia'' can infect many different types of organs, but are most notable for the infections of the [[testes]] and [[ovaries]] of their hosts altering the reproduction abilities of these. ''Wolbachia'' species are ubiquitous in mature eggs, but not mature sperm. Only infected females, therefore, pass the infection on to their offspring. ''Wolbachia'' bacteria maximize their spread by altering the reproductive capabilities of their hosts, in favour for the infected females. Several different [[phenotype]]s have been observed, including:

* Male killing occurs when infected males die during larval development, which increases the rate of born, infected females.<ref>{{cite journal | vauthors = Hackett KJ, Lynn DE, Williamson DL, Ginsberg AS, Whitcomb RF | title = Cultivation of the Drosophila sex-ratio spiroplasma | journal = Science | volume = 232 | issue = 4755 | pages = 1253–1255 | date = June 1986 | pmc = 1689827 | doi = 10.1098/rspb.1999.0698 | pmid = 17810745 }}</ref>
* [[Feminization (biology)|Feminization]] results in infected males that develop as females or infertile pseudofemales. This is especially prevalent in [[Lepidoptera]] species such as the adzuki bean borer (''[[Ostrinia scapulalis]]'').<ref>{{cite journal | vauthors = Fujii Y, Kageyama D, Hoshizaki S, Ishikawa H, Sasaki T | title = Transfection of Wolbachia in Lepidoptera: the feminizer of the adzuki bean borer Ostrinia scapulalis causes male killing in the Mediterranean flour moth Ephestia kuehniella | journal = Proceedings. Biological Sciences | volume = 268 | issue = 1469 | pages = 855–859 | date = April 2001 | pmid = 11345332 | pmc = 1088680 | doi = 10.1098/rspb.2001.1593 }}</ref>
* [[Parthenogenesis]] is reproduction of infected females without males. Some scientists have suggested that parthenogenesis may always be attributable to the effects of ''Wolbachia,''<ref>{{cite book | vauthors = Tortora GJ, Funke BR, Case CL |title=Microbiology: an introduction |publisher=Pearson Benjamin Cummings |year=2007 |isbn=978-0-8053-4790-6 |url-access=registration |url=https://archive.org/details/microbiologyintr0009tort }}</ref> though this is not the case for the [[marbled crayfish]].<ref>{{cite journal | url=https://pubmed.ncbi.nlm.nih.gov/15281058/ | pmid=15281058 | doi=10.1002/jmor.10250 | title=Life stages and reproductive components of the Marmorkrebs (Marbled crayfish), the first parthenogenetic decapod crustacean | journal=Journal of Morphology | date=September 2004 | volume=261 | issue=3 | pages=286–311 | last1=Vogt | first1=Günter | last2=Tolley | first2=Laura | last3=Scholtz | first3=Gerhard | s2cid=24702276 }}</ref> An example of parthenogenesis induced by presence of ''Wolbachia'' are some species within the ''[[Trichogramma]]'' parasitoid wasp genus,<ref name="Knight2001">{{cite journal | vauthors = Knight J | title = Meet the Herod bug | journal = Nature | volume = 412 | issue = 6842 | pages = 12–14 | date = July 2001 | pmid = 11452274 | doi = 10.1038/35083744 | s2cid = 205018882 | doi-access = free | bibcode = 2001Natur.412...12K }}</ref> which have evolved to procreate without males due to the presence of ''Wolbachia''. Males are rare in this genus of wasp, possibly because many have been killed by that same strain of ''Wolbachia''.<ref>{{cite journal |title=Garden Friends & Foes: Trichogramma Wasps |url=http://whatcom.wsu.edu/ag/homehort/pest/trichogramma.htm | vauthors = Murray T |journal=Weeder's Digest |publisher=Washington State University Whatcom County Extension |access-date=16 July 2009 |archive-url=https://web.archive.org/web/20090621192656/http://whatcom.wsu.edu/ag/homehort/pest/trichogramma.htm |archive-date=2009-06-21 |url-status=dead }}<!-- possibly oclc=58592363 --></ref>
* [[Cytoplasmic incompatibility]] is the inability of ''Wolbachia''-infected males to successfully reproduce with uninfected females or females infected with another ''Wolbachia'' [[Strain (biology)|strain]]. This reduces the reproductive success of those uninfected females and therefore promotes the infecting strain. In the cytoplasmic incompatibility mechanism, ''Wolbachia'' interferes with the parental chromosomes during the first [[Mitosis|mitotic]] divisions to the extent that they can no longer divide in synchrony.<ref>{{cite journal | vauthors = Breeuwer JA, Werren JH | title = Microorganisms associated with chromosome destruction and reproductive isolation between two insect species | journal = Nature | volume = 346 | issue = 6284 | pages = 558–560 | date = August 1990 | pmid = 2377229 | doi = 10.1038/346558a0 | s2cid = 4255393 | bibcode = 1990Natur.346..558B }}</ref>

== Effects of sexual differentiation in hosts ==
Several host species, such as those within the genus ''Trichogramma'', are so dependent on sexual differentiation of ''Wolbachia'' that they are unable to reproduce effectively without the bacteria in their bodies, and some might even be unable to survive uninfected.<ref>{{Cite journal | vauthors = Werren JH |date=February 2003 |title=Invasion of the Gender Benders: by manipulating sex and reproduction in their hosts, many parasites improve their own odds of survival and may shape the evolution of sex itself |journal=[[Natural History (magazine)|Natural History]] |volume=112 |issue=1 |page=58 |issn=0028-0712 |oclc=1759475}}</ref>

One study on infected [[Oniscus asellus|woodlice]] showed the broods of infected organisms had a higher proportion of females than their uninfected counterparts.<ref>{{cite journal | vauthors = Rigaud T, Moreau J, Juchault P | title = Wolbachia infection in the terrestrial isopod oniscus asellus: sex ratio distortion and effect on fecundity | journal = Heredity | volume = 83 | issue = # (Pt 4) | pages = 469–475 | date = October 1999 | pmid = 10583549 | doi = 10.1038/sj.hdy.6885990 | doi-access = free }} However, the broods also often consisted of fewer eggs than the broods of the uninfected ''Oniscus asellus''.</ref>

''Wolbachia'', especially ''Wolbachia''-caused cytoplasmic incompatibility, may be important in promoting speciation.<ref>{{cite journal | vauthors = Bordenstein SR, O'Hara FP, Werren JH | title = Wolbachia-induced incompatibility precedes other hybrid incompatibilities in Nasonia | journal = Nature | volume = 409 | issue = 6821 | pages = 707–710 | date = February 2001 | pmid = 11217858 | doi = 10.1038/35055543 | s2cid = 1867358 | bibcode = 2001Natur.409..707B }}</ref><ref>{{cite journal | vauthors = Zimmer C | title = Wolbachia. A tale of sex and survival | journal = Science | volume = 292 | issue = 5519 | pages = 1093–1095 | date = May 2001 | pmid = 11352061 | doi = 10.1126/science.292.5519.1093 | s2cid = 37441675 | author-link = Carl Zimmer }}</ref><ref>{{cite journal | vauthors = Telschow A, Flor M, Kobayashi Y, Hammerstein P, Werren JH | title = Wolbachia-induced unidirectional cytoplasmic incompatibility and speciation: mainland-island model | journal = PLOS ONE | volume = 2 | issue = 8 | pages = e701 | date = August 2007 | pmid = 17684548 | pmc = 1934337 | doi = 10.1371/journal.pone.0000701 | veditors = Rees M | doi-access = free | bibcode = 2007PLoSO...2..701T }}</ref> ''Wolbachia'' strains that distort the sex ratio may alter their host's pattern of sexual selection in nature,<ref>{{cite journal | vauthors = Charlat S, Reuter M, Dyson EA, Hornett EA, Duplouy A, Davies N, Roderick GK, Wedell N, Hurst GD | title = Male-killing bacteria trigger a cycle of increasing male fatigue and female promiscuity | journal = Current Biology | volume = 17 | issue = 3 | pages = 273–277 | date = February 2007 | pmid = 17276921 | doi = 10.1016/j.cub.2006.11.068 | s2cid = 18564109 | doi-access = free | bibcode = 2007CBio...17..273C }}</ref><ref>{{cite journal | vauthors = Jiggins FM, Hurst GD, Majerus ME | title = Sex-ratio-distorting Wolbachia causes sex-role reversal in its butterfly host | journal = Proceedings. Biological Sciences | volume = 267 | issue = 1438 | pages = 69–73 | date = January 2000 | pmid = 10670955 | pmc = 1690502 | doi = 10.1098/rspb.2000.0968 }}</ref> and also engender strong selection to prevent their action, leading to some of the fastest examples of natural selection in natural populations.<ref>{{cite journal | vauthors = Charlat S, Hornett EA, Fullard JH, Davies N, Roderick GK, Wedell N, Hurst GD | title = Extraordinary flux in sex ratio | journal = Science | volume = 317 | issue = 5835 | pages = 214 | date = July 2007 | pmid = 17626876 | doi = 10.1126/science.1143369 | s2cid = 45723069 | bibcode = 2007Sci...317..214C }}</ref>

The male killing and feminization effects of ''Wolbachia'' infections can also lead to speciation in their hosts. For example, populations of the pill woodlouse, ''[[Armadillidium vulgare]]'' which are exposed to the feminizing effects of ''Wolbachia'', have been known to lose their female-determining chromosome.<ref name=":0">{{cite journal | vauthors = Charlat S, Hurst GD, Merçot H | title = Evolutionary consequences of Wolbachia infections | journal = Trends in Genetics | volume = 19 | issue = 4 | pages = 217–223 | date = April 2003 | pmid = 12683975 | doi = 10.1016/S0168-9525(03)00024-6 }}</ref> In these cases, only the presence of ''Wolbachia'' can cause an individual to develop into a female.<ref name=":0"/> Cryptic species of ground wētā (''[[Hemiandrus maculifrons]]'' complex) are host to different lineages of ''Wolbachia'' which might explain their speciation without ecological or geographical separation.<ref>{{cite journal | vauthors = Bridgeman B, Morgan-Richards M, Wheeler D, Trewick SA | title = First detection of Wolbachia in the New Zealand biota | journal = PLOS ONE | volume = 13 | issue = 4 | pages = e0195517 | date = 2018-04-25 | pmid = 29694414 | pmc = 5918756 | doi = 10.1371/journal.pone.0195517 | doi-access = free | bibcode = 2018PLoSO..1395517B }}</ref><ref>{{Cite journal| vauthors = Taylor-Smith BL, Trewick SA, Morgan-Richards M |date= October 2016 |title=Three new ground wētā species and a redescription of Hemiandrus maculifrons|journal=New Zealand Journal of Zoology|volume=43|issue=4|pages=363–383|doi=10.1080/03014223.2016.1205109|s2cid=88565199|issn=0301-4223}}</ref>

===Effect on aromatase===

The enzyme [[aromatase]] is found to mediate sex-change in many species of fish. ''Wolbachia'' can affect the activity of aromatase in developing fish embryos.<ref>{{cite web | vauthors = Cormier Z | date = 2014 |url=https://ourblueplanet.bbcearth.com/blog/?article=incredible-sex-changing-fish-from-blue-planet |url-status=dead |archive-url= https://web.archive.org/web/20171201124634/http://ourblueplanet.bbcearth.com/blog/?article=incredible-sex-changing-fish-from-blue-planet |archive-date=2017-12-01 |title=Fish are the sex-switching masters of the animal kingdom | work = Our Blue Planet | publisher = British Broadcasting System (BBC) }}</ref>

==Mechanism of Host Transfer ==

=== Step 1: physical transfer ===

==== a. Predator-prey interactions ====
''Wolbachia'' may transfer from prey to predator through the digestive system. To do so, ''Wolbachia'' needs to first survive through the lumen secretion and then enter the host tissue through the gut epithelium.<ref name="sfamjournals.onlinelibrary.wiley.com">{{Cite journal |last1=Sicard |first1=Mathieu |last2=Dittmer |first2=Jessica |last3=Grève |first3=Pierre |last4=Bouchon |first4=Didier |last5=Braquart-Varnier |first5=Christine |date=December 2014 |title=A host as an ecosystem: W olbachia coping with environmental constraints |url=https://sfamjournals.onlinelibrary.wiley.com/doi/10.1111/1462-2920.12573 |journal=Environmental Microbiology |language=en |volume=16 |issue=12 |pages=3583–3607 |doi=10.1111/1462-2920.12573 |pmid=25052143 |bibcode=2014EnvMi..16.3583S |issn=1462-2912}}</ref> This route does not seem to occur frequently due to little evidence.<ref>{{Cite journal |last1=Sanaei |first1=Ehsan |last2=Charlat |first2=Sylvain |last3=Engelstädter |first3=Jan |date=April 2021 |title=Wolbachia host shifts: routes, mechanisms, constraints and evolutionary consequences |url=https://onlinelibrary.wiley.com/doi/10.1111/brv.12663 |journal=Biological Reviews |language=en |volume=96 |issue=2 |pages=433–453 |doi=10.1111/brv.12663 |pmid=33128345 |hdl=10072/417945 |issn=1464-7931|hdl-access=free }}</ref>

==== b. Host–parasitoid/parasite interactions ====
This may be one of the most common routes of ''Wolbachia'' host shifts. Compared to predator-prey interactions, the physical association between the host and parasites typically lasts longer, occurs at various developmental stages, and enables ''Wolbachia'' to directly contact various tissues.

Since this interaction may expose both sides to microbial exchange, one strategy for understanding the direction of transfer is to assess ''Wolbachia''<nowiki/>'s presence in close relatives on both sides, as the donor side generally has a larger diversity of infection.<ref>{{Cite journal |last=Johannesen |first=Jes |date=February 2017 |title=Tracing the history and ecological context of Wolbachia double infection in a specialist host ( Urophora cardui )—parasitoid ( Eurytoma serratulae ) system |journal=Ecology and Evolution |language=en |volume=7 |issue=3 |pages=986–996 |doi=10.1002/ece3.2713 |issn=2045-7758 |pmc=5288247 |pmid=28168034|bibcode=2017EcoEv...7..986J }}</ref>

One parasitoid species can infect multiple shared hosts, and one host species can infect multiple parasitoids. For instance, parthenogenesis-inducing ''Wolbachia'' can spread between ''Trichogramma'' parasitoid wasps sharing host eggs.<ref>{{Cite journal |last1=Huigens |first1=M. E. |last2=Luck |first2=R. F. |last3=Klaassen |first3=R. H. G. |last4=Maas |first4=M. F. P. M. |last5=Timmermans |first5=M. J. T. N. |last6=Stouthamer |first6=R. |date=May 2000 |title=Infectious parthenogenesis |url=https://www.nature.com/articles/35012066 |journal=Nature |language=en |volume=405 |issue=6783 |pages=178–179 |doi=10.1038/35012066 |pmid=10821272 |bibcode=2000Natur.405..178H |issn=0028-0836}}</ref>

Parasites can also serve as a vector between infected and uninfected hosts without being infected. When the mouthparts and ovipositors of [[aphelinid]] parasitoid wasps become contaminated through feeding ''Wolbachia''-infected ''[[Bemisia tabaci]]'', it can infect the next host.<ref>{{Cite journal |last1=Ahmed |first1=Muhammad Z. |last2=Li |first2=Shao-Jian |last3=Xue |first3=Xia |last4=Yin |first4=Xiang-Jie |last5=Ren |first5=Shun-Xiang |last6=Jiggins |first6=Francis M. |last7=Greeff |first7=Jaco M. |last8=Qiu |first8=Bao-Li |date=2015-02-12 |editor-last=Hurst |editor-first=Greg |title=The Intracellular Bacterium Wolbachia Uses Parasitoid Wasps as Phoretic Vectors for Efficient Horizontal Transmission |journal=PLOS Pathogens |language=en |volume=11 |issue=2 |pages=e1004672 |doi=10.1371/journal.ppat.1004672 |doi-access=free |issn=1553-7374 |pmc=4347858 |pmid=25675099}}</ref>

==== c. Shared plant and other food sources ====
This route applies to microbes that can survive either within or on the surface of the food. Experiments demonstrated that the ''Wolbachia'' wAlbB strain can survive extracellularly for up to 7 days,<ref>{{Cite journal |last1=Rasgon |first1=Jason L. |last2=Gamston |first2=Courtney E. |last3=Ren |first3=Xiaoxia |date=November 2006 |title=Survival of Wolbachia pipientis in Cell-Free Medium |journal=Applied and Environmental Microbiology |language=en |volume=72 |issue=11 |pages=6934–6937 |doi=10.1128/AEM.01673-06 |issn=0099-2240 |pmc=1636208 |pmid=16950898|bibcode=2006ApEnM..72.6934R }}</ref> and up to 50 days for some strains in cotton leaf [[phloem]] vessels.<ref>{{Cite journal |last1=Li |first1=Shao-Jian |last2=Ahmed |first2=Muhammad Z |last3=Lv |first3=Ning |last4=Shi |first4=Pei-Qiong |last5=Wang |first5=Xing-Min |last6=Huang |first6=Ji-Lei |last7=Qiu |first7=Bao-Li |date=2017-04-01 |title=Plant–mediated horizontal transmission of Wolbachia between whiteflies |journal=The ISME Journal |language=en |volume=11 |issue=4 |pages=1019–1028 |doi=10.1038/ismej.2016.164 |issn=1751-7362 |pmc=5364347 |pmid=27935594|bibcode=2017ISMEJ..11.1019L }}</ref>

Plants are one of the best platforms for this route. By physical contact between arthropod mouthparts and plant tissue, the ''Wolbachia'' inhabiting the salivary glands of some insects may be transferred to the plants.<ref>{{Cite journal |last1=Dobson |first1=Stephen L. |last2=Bourtzis |first2=Kostas |last3=Braig |first3=Henk R. |last4=Jones |first4=Brian F. |last5=Zhou |first5=Weiguo |last6=Rousset |first6=François |last7=O'Neill |first7=Scott L. |date=February 1999 |title=Wolbachia infections are distributed throughout insect somatic and germ line tissues |journal=Insect Biochemistry and Molecular Biology |language=en |volume=29 |issue=2 |pages=153–160 |doi=10.1016/S0965-1748(98)00119-2|pmid=10196738 |doi-access=free |bibcode=1999IBMB...29..153D }}</ref> As a result, arthropod species feeding on the same plants may share common ''Wolbachia'' strains.

Other insect food sources may also mediate ''Wolbachia'' horizontal transfer, such as the sharing of dung patches between two Malagasy dung beetle species.<ref>{{Cite journal |last1=Miraldo |first1=Andreia |last2=Duplouy |first2=Anne |date=2019-05-08 |title=High Wolbachia Strain Diversity in a Clade of Dung Beetles Endemic to Madagascar |journal=Frontiers in Ecology and Evolution |volume=7 |doi=10.3389/fevo.2019.00157 |doi-access=free |issn=2296-701X}}</ref>

=== Step 2: survival and proliferation in the new host ===
The [[pathogen-associated molecular pattern]]s (PAMPs) in the bacteria, such as [[peptidoglycan]], can activate the host's innate immune responses.<ref>{{Cite journal |last1=Zaidman-Rémy |first1=Anna |last2=Hervé |first2=Mireille |last3=Poidevin |first3=Mickael |last4=Pili-Floury |first4=Sébastien |last5=Kim |first5=Min-Sung |last6=Blanot |first6=Didier |last7=Oh |first7=Byung-Ha |last8=Ueda |first8=Ryu |last9=Mengin-Lecreulx |first9=Dominique |last10=Lemaitre |first10=Bruno |date=April 2006 |title=The Drosophila Amidase PGRP-LB Modulates the Immune Response to Bacterial Infection |url=https://linkinghub.elsevier.com/retrieve/pii/S1074761306001774 |journal=Immunity |language=en |volume=24 |issue=4 |pages=463–473 |doi=10.1016/j.immuni.2006.02.012|pmid=16618604 }}</ref><ref>{{Cite journal |last1=Otten |first1=Christian |last2=Brilli |first2=Matteo |last3=Vollmer |first3=Waldemar |last4=Viollier |first4=Patrick H. |last5=Salje |first5=Jeanne |date=January 2018 |title=Peptidoglycan in obligate intracellular bacteria |journal=Molecular Microbiology |language=en |volume=107 |issue=2 |pages=142–163 |doi=10.1111/mmi.13880 |issn=0950-382X |pmc=5814848 |pmid=29178391}}</ref> In response, some ''Wolbachia'' strains have a unique functional peptidoglycan amidase (AmiDwol) that cleaves its bacterial cell wall so that it can escape from immune responses.<ref>{{Cite journal |last1=Eleftherianos |first1=Ioannis |last2=Atri |first2=Jaishri |last3=Accetta |first3=Julia |last4=Castillo |first4=Julio C. |date=2013 |title=Endosymbiotic bacteria in insects: guardians of the immune system? |journal=Frontiers in Physiology |volume=4 |page=46 |doi=10.3389/fphys.2013.00046 |doi-access=free |issn=1664-042X |pmc=3597943 |pmid=23508299}}</ref><ref>{{Cite journal |last1=Wilmes |first1=Miriam |last2=Meier |first2=Kirstin |last3=Schiefer |first3=Andrea |last4=Josten |first4=Michaele |last5=Otten |first5=Christian F. |last6=Klöckner |first6=Anna |last7=Henrichfreise |first7=Beate |last8=Vollmer |first8=Waldemar |last9=Hoerauf |first9=Achim |last10=Pfarr |first10=Kenneth |date=2017-08-04 |title=AmiD Is a Novel Peptidoglycan Amidase in Wolbachia Endosymbionts of Drosophila melanogaster |journal=Frontiers in Cellular and Infection Microbiology |volume=7 |page=353 |doi=10.3389/fcimb.2017.00353 |doi-access=free |issn=2235-2988 |pmc=5543032 |pmid=28824885}}</ref> Besides the peptidoglycans, cell-to-cell movements of ''Wolbachia'' can also cause oxidative stress to the host and trigger the host's immune response.<ref>{{Cite journal |last1=White |first1=Pamela M. |last2=Pietri |first2=Jose E. |last3=Debec |first3=Alain |last4=Russell |first4=Shelbi |last5=Patel |first5=Bhavin |last6=Sullivan |first6=William |date=April 2017 |editor-last=Drake |editor-first=Harold L. |title=Mechanisms of Horizontal Cell-to-Cell Transfer of Wolbachia spp. in Drosophila melanogaster |journal=Applied and Environmental Microbiology |language=en |volume=83 |issue=7 |doi=10.1128/AEM.03425-16 |issn=0099-2240 |pmc=5359480 |pmid=28087534|bibcode=2017ApEnM..83E3425W }}</ref> Therefore, ''Wolbachia'' has a triple-layer vacuole that acts as a mechanical shield to protect it from cellular immune responses.<ref name="sfamjournals.onlinelibrary.wiley.com"/>

=== Step 3: vertical transmission ===
Vertical transmission requires ''Wolbachia'' to reach germ line cells and maintain in the zygote. ''Wolbachia'' may initially occupy somatic stem cells as a stable reservoir<ref>{{Cite journal |last1=Frydman |first1=Horacio M. |last2=Li |first2=Jennifer M. |last3=Robson |first3=Drew N. |last4=Wieschaus |first4=Eric |date=May 2006 |title=Somatic stem cell niche tropism in Wolbachia |url=https://www.nature.com/articles/nature04756 |journal=Nature |language=en |volume=441 |issue=7092 |pages=509–512 |doi=10.1038/nature04756 |pmid=16724067 |bibcode=2006Natur.441..509F |issn=0028-0836}}</ref> and then use the host's [[vitellogenin]] transovarial transportation system to enter the [[oocyte]].<ref>{{Cite journal |last1=Guo |first1=Yan |last2=Hoffmann |first2=Ary A. |last3=Xu |first3=Xiao-Qin |last4=Mo |first4=Pei-Wen |last5=Huang |first5=Hai-Jian |last6=Gong |first6=Jun-Tao |last7=Ju |first7=Jia-Fei |last8=Hong |first8=Xiao-Yue |date=2018-08-28 |title=Vertical Transmission of Wolbachia Is Associated With Host Vitellogenin in Laodelphax striatellus |journal=Frontiers in Microbiology |volume=9 |page=2016 |doi=10.3389/fmicb.2018.02016 |doi-access=free |issn=1664-302X |pmc=6127624 |pmid=30233514}}</ref> Once ''Wolbachia'' enter the zygote, they need to reach important host tissues without disrupting the embryo's development. This can be achieved using the host cytoskeleton, by bundling ''Wolbachia'' protein WD0830 to host actin filaments. They can also increase the division rate of germ-line stem cells to localize and increase their titer.<ref>{{Cite journal |last1=Pietri |first1=Jose E. |last2=DeBruhl |first2=Heather |last3=Sullivan |first3=William |date=December 2016 |title=The rich somatic life of Wolbachia |journal=MicrobiologyOpen |language=en |volume=5 |issue=6 |pages=923–936 |doi=10.1002/mbo3.390 |issn=2045-8827 |pmc=5221451 |pmid=27461737}}</ref><ref>{{Cite journal |last=Landmann |first=Frédéric |date=2019-04-12 |editor-last=Cossart |editor-first=Pascale |editor2-last=Roy |editor2-first=Craig R. |editor3-last=Sansonetti |editor3-first=Philippe |title=The Wolbachia Endosymbionts |url=https://journals.asm.org/doi/10.1128/microbiolspec.BAI-0018-2019 |journal=Microbiology Spectrum |language=en |volume=7 |issue=2 |doi=10.1128/microbiolspec.BAI-0018-2019 |pmid=30953430 |issn=2165-0497}}</ref><ref>{{Cite journal |last1=Guo |first1=Yan |last2=Gong |first2=Jun-Tao |last3=Mo |first3=Pei-Wen |last4=Huang |first4=Hai-Jian |last5=Hong |first5=Xiao-Yue |date=July 2019 |title=Wolbachia localization during Laodelphax striatellus embryogenesis |url=https://linkinghub.elsevier.com/retrieve/pii/S0022191018305079 |journal=Journal of Insect Physiology |language=en |volume=116 |pages=125–133 |doi=10.1016/j.jinsphys.2019.05.006|pmid=31128084 |bibcode=2019JInsP.116..125G }}</ref> Under natural conditions, successful vertical transmission of ''Wolbachia'' is challenging.

=== Step 4: spread within the host population ===
Invasion of a new population likely stems from specific phenotypic effects, including reproductive manipulations and/or providing direct fitness benefits to their female hosts.<ref>{{Cite journal |last=Werren |first=John H. |date=January 1997 |title=BIOLOGY OF ''WOLBACHIA'' |url=https://www.annualreviews.org/doi/10.1146/annurev.ento.42.1.587 |journal=Annual Review of Entomology |language=en |volume=42 |issue=1 |pages=587–609 |doi=10.1146/annurev.ento.42.1.587 |pmid=15012323 |issn=0066-4170}}</ref><ref>{{Cite journal |last1=Stouthamer |first1=R. |last2=Breeuwer |first2=J. A. J. |last3=Hurst |first3=G. D. D. |date=October 1999 |title=Wolbachia Pipientis : Microbial Manipulator of Arthropod Reproduction |url=https://www.annualreviews.org/doi/10.1146/annurev.micro.53.1.71 |journal=Annual Review of Microbiology |language=en |volume=53 |issue=1 |pages=71–102 |doi=10.1146/annurev.micro.53.1.71 |pmid=10547686 |issn=0066-4227}}</ref><ref>{{Cite journal |last1=Fenton |first1=Andrew |last2=Johnson |first2=Karyn N. |last3=Brownlie |first3=Jeremy C. |last4=Hurst |first4=Gregory D. D. |date=September 2011 |title=Solving the Wolbachia Paradox: Modeling the Tripartite Interaction between Host, Wolbachia , and a Natural Enemy |url=https://www.journals.uchicago.edu/doi/10.1086/661247 |journal=The American Naturalist |language=en |volume=178 |issue=3 |pages=333–342 |doi=10.1086/661247 |pmid=21828990 |hdl=10072/40897 |issn=0003-0147|hdl-access=free }}</ref><ref>{{Cite journal |last1=Zug |first1=Roman |last2=Hammerstein |first2=Peter |date=February 2015 |title=Bad guys turned nice? A critical assessment of Wolbachia mutualisms in arthropod hosts |url=https://onlinelibrary.wiley.com/doi/10.1111/brv.12098 |journal=Biological Reviews |language=en |volume=90 |issue=1 |pages=89–111 |doi=10.1111/brv.12098 |pmid=24618033 |issn=1464-7931}}</ref>

Upon transferring into a new host, ''Wolbachia'' may retain its original phenotypic effects, induce a different phenotype, or have no detectable effect. For instance, a strain that induces male killing in the moth ''[[Cadra cautella]]'' induced cytoplasmic incompatibility in a novel moth host ''[[Ephestia kuehniella]]''.<ref>{{Cite journal |last1=Sasaki |first1=Tetsuhiko |last2=Kubo |first2=Takeo |last3=Ishikawa |first3=Hajime |date=2002-11-01 |title=Interspecific Transfer of Wolbachia Between Two Lepidopteran Insects Expressing Cytoplasmic Incompatibility: A Wolbachia Variant Naturally Infecting Cadra cautella Causes Male Killing in Ephestia kuehniella |url=https://academic.oup.com/genetics/article/162/3/1313/6053022 |journal=Genetics |language=en |volume=162 |issue=3 |pages=1313–1319 |doi=10.1093/genetics/162.3.1313 |issn=1943-2631 |pmc=1462327 |pmid=12454075}}</ref>

==Fitness advantages by ''Wolbachia'' infections ==
''Wolbachia'' infection has been linked to viral resistance in ''[[Drosophila melanogaster]]'', ''[[Drosophila simulans]]'', and mosquito species. Flies, including mosquitoes,<ref>{{cite journal | vauthors = Johnson KN | title = The Impact of Wolbachia on Virus Infection in Mosquitoes | journal = Viruses | volume = 7 | issue = 11 | pages = 5705–5717 | date = November 2015 | pmid = 26556361 | pmc = 4664976 | doi = 10.3390/v7112903 | quote = In contrast [to natural infection], stable transinfection of Wolbachia into heterologous mosquito hosts clearly produces antiviral effects against arboviruses including DENV [dengue virus], WNV [West Nile virus], YFV [yellow fever virus] and CHIKV [Chikungunya virus]....as adaption occurs these effects may decrease | doi-access = free }}</ref> infected with the bacteria are more resistant to RNA viruses such as [[Drosophila C virus]], [[norovirus]], [[Flock House virus|flock house virus]], [[cricket paralysis virus]], [[chikungunya virus]], and [[West Nile virus]].<ref>{{cite journal | vauthors = Teixeira L, Ferreira A, Ashburner M | title = The bacterial symbiont Wolbachia induces resistance to RNA viral infections in Drosophila melanogaster | journal = PLOS Biology | volume = 6 | issue = 12 | pages = e2 | date = December 2008 | pmid = 19222304 | pmc = 2605931 | doi = 10.1371/journal.pbio.1000002 | veditors = Keller L | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hedges LM, Brownlie JC, O'Neill SL, Johnson KN | title = Wolbachia and virus protection in insects | journal = Science | volume = 322 | issue = 5902 | pages = 702 | date = October 2008 | pmid = 18974344 | doi = 10.1126/science.1162418 | s2cid = 206514799 | bibcode = 2008Sci...322..702H }}</ref><ref>{{cite journal | vauthors = Glaser RL, Meola MA | title = The native Wolbachia endosymbionts of Drosophila melanogaster and Culex quinquefasciatus increase host resistance to West Nile virus infection | journal = PLOS ONE | volume = 5 | issue = 8 | pages = e11977 | date = August 2010 | pmid = 20700535 | pmc = 2916829 | doi = 10.1371/journal.pone.0011977 | doi-access = free | bibcode = 2010PLoSO...511977G }}</ref>

In the common house mosquito, higher levels of ''Wolbachia'' were correlated with more insecticide resistance.<ref>{{cite journal | vauthors = Berticat C, Rousset F, Raymond M, Berthomieu A, Weill M | title = High Wolbachia density in insecticide-resistant mosquitoes | journal = Proceedings. Biological Sciences | volume = 269 | issue = 1498 | pages = 1413–1416 | date = July 2002 | pmid = 12079666 | pmc = 1691032 | doi = 10.1098/rspb.2002.2022 }}</ref>

In [[leafminer]]s of the species ''[[Phyllonorycter blancardella]]'', ''Wolbachia'' bacteria help their hosts produce green islands on yellowing tree leaves, that is, small areas of leaf remaining fresh, allowing the hosts to continue feeding while growing to their adult forms. Larvae treated with [[tetracycline]], which kills ''Wolbachia'', lose this ability and subsequently only 13% emerge successfully as adult moths.<ref>{{cite journal | vauthors = Kaiser W, Huguet E, Casas J, Commin C, Giron D | title = Plant green-island phenotype induced by leaf-miners is mediated by bacterial symbionts | journal = Proceedings. Biological Sciences | volume = 277 | issue = 1692 | pages = 2311–2319 | date = August 2010 | pmid = 20356892 | pmc = 2894905 | doi = 10.1098/rspb.2010.0214 }}</ref>

''[[Muscidifurax uniraptor]], a'' [[parasitoid wasp]], also benefits from hosting ''Wolbachia'' bacteria.<ref>{{cite journal | vauthors = Zchori-Fein E, Gottlieb Y, Coll M | title = Wolbachia density and host fitness components in Muscidifurax uniraptor (Hymenoptera: pteromalidae) | journal = Journal of Invertebrate Pathology | volume = 75 | issue = 4 | pages = 267–272 | date = May 2000 | pmid = 10843833 | doi = 10.1006/jipa.2000.4927 | bibcode = 2000JInvP..75..267Z }}</ref>

In the parasitic [[Filarioidea|filarial nematode]] species responsible for [[Lymphatic filariasis|elephantiasis]], such as ''[[Brugia malayi]]'' and ''[[Wuchereria bancrofti]]'', ''Wolbachia'' has become an obligate [[endosymbiont]] and provides the host with chemicals necessary for its reproduction and survival.<ref name="pmid15780005"/> Elimination of the ''Wolbachia'' symbionts through antibiotic treatment therefore prevents reproduction of the nematode, and eventually results in its premature death.

Some ''Wolbachia'' species that infect arthropods also provide some metabolic provisioning to their hosts. In ''Drosophila melanogaster'', ''Wolbachia'' is found to mediate iron metabolism under nutritional stress<ref>{{cite journal | vauthors = Brownlie JC, Cass BN, Riegler M, Witsenburg JJ, Iturbe-Ormaetxe I, McGraw EA, O'Neill SL | title = Evidence for metabolic provisioning by a common invertebrate endosymbiont, Wolbachia pipientis, during periods of nutritional stress | journal = PLOS Pathogens | volume = 5 | issue = 4 | pages = e1000368 | date = April 2009 | pmid = 19343208 | pmc = 2657209 | doi = 10.1371/journal.ppat.1000368 | doi-access = free }}</ref> and in ''[[Cimex lectularius]]'', the ''Wolbachia'' strain ''cCle'' helps the host to synthesize [[B vitamins]].<ref>{{cite journal | vauthors = Nikoh N, Hosokawa T, Moriyama M, Oshima K, Hattori M, Fukatsu T | title = Evolutionary origin of insect-Wolbachia nutritional mutualism | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 28 | pages = 10257–10262 | date = July 2014 | pmid = 24982177 | pmc = 4104916 | doi = 10.1073/pnas.1409284111 | doi-access = free | bibcode = 2014PNAS..11110257N }}</ref>

Some ''Wolbachia'' strains have increased their prevalence by increasing their hosts' fecundity. ''Wolbachia'' strains captured from 1988 in southern California still induce a [[Fecundity selection|fecundity]] deficit, but nowadays the fecundity deficit is replaced with a fecundity advantage such that infected ''[[Drosophila simulans]]'' produces more offspring than the uninfected ones.<ref>{{cite journal | vauthors = Weeks AR, Turelli M, Harcombe WR, Reynolds KT, Hoffmann AA | title = From parasite to mutualist: rapid evolution of Wolbachia in natural populations of Drosophila | journal = PLOS Biology | volume = 5 | issue = 5 | pages = e114 | date = May 2007 | pmid = 17439303 | pmc = 1852586 | doi = 10.1371/journal.pbio.0050114 | doi-access = free }}</ref>

==Life-history consequences of ''Wolbachia'' infection ==
''Wolbachia'' often manipulates host reproduction and life-history in a way that favours its own propagation. In the [[Pharaoh ant]], ''Wolbachia'' infection correlates with increased colony-level production of reproductives (i.e., greater reproductive investment), and earlier onset of reproductive production (i.e., shorter life-cycle). Infected colonies also seem to grow more rapidly.<ref>{{cite journal | vauthors = Singh R, Linksvayer TA | title = ''Wolbachia''-infected ant colonies have increased reproductive investment and an accelerated life cycle | journal = The Journal of Experimental Biology | volume = 223 | issue = Pt 9 | pages = jeb.220079 | date = May 2020 | pmid = 32253286 | doi = 10.1242/jeb.220079 | s2cid = 215409488 | doi-access = free }}</ref> There is substantial evidence that the presence of ''Wolbachia'' that induce parthenogenesis have put pressure on species to reproduce primarily or entirely this way.<ref>{{Cite journal| vauthors = Gottlieb Y, Zchori-Fein E |date=2001 |title=Irreversible thelytokous reproduction in Muscidifurax uniraptor |journal=Entomologia Experimentalis et Applicata |volume=100 |issue=3 |pages=271–278 |doi=10.1046/j.1570-7458.2001.00874.x |bibcode=2001EEApp.100..271G |s2cid=54687768|issn=1570-7458}}</ref>

Additionally, ''Wolbachia'' has been seen to decrease the lifespan of ''[[Aedes aegypti]]'', carriers of mosquito-borne diseases, and it decreases their efficacy of pathogen transmission because older mosquitoes are more likely to have become carriers of one of those diseases.<ref>{{cite journal | vauthors = Hoffmann AA, Montgomery BL, Popovici J, Iturbe-Ormaetxe I, Johnson PH, Muzzi F, Greenfield M, Durkan M, Leong YS, Dong Y, Cook H, Axford J, Callahan AG, Kenny N, Omodei C, McGraw EA, Ryan PA, Ritchie SA, Turelli M, O'Neill SL | title = Successful establishment of Wolbachia in Aedes populations to suppress dengue transmission | journal = Nature | volume = 476 | issue = 7361 | pages = 454–457 | date = August 2011 | pmid = 21866160 | doi = 10.1038/nature10356 | s2cid = 4316652 | bibcode = 2011Natur.476..454H }}</ref> This has been exploited as a method for pest control.

==Genomics==
The first ''Wolbachia'' genome to be determined was that of strain wMel, which infects ''D. melanogaster'' fruit flies.<ref name="pmid15024419">{{cite journal | vauthors = Wu M, Sun LV, Vamathevan J, Riegler M, Deboy R, Brownlie JC, McGraw EA, Martin W, Esser C, Ahmadinejad N, Wiegand C, Madupu R, Beanan MJ, Brinkac LM, Daugherty SC, Durkin AS, Kolonay JF, Nelson WC, Mohamoud Y, Lee P, Berry K, Young MB, Utterback T, Weidman J, Nierman WC, Paulsen IT, Nelson KE, Tettelin H, O'Neill SL, Eisen JA | title = Phylogenomics of the reproductive parasite Wolbachia pipientis wMel: a streamlined genome overrun by mobile genetic elements | journal = PLOS Biology | volume = 2 | issue = 3 | pages = E69 | date = March 2004 | pmid = 15024419 | pmc = 368164 | doi = 10.1371/journal.pbio.0020069 | doi-access = free }}</ref> This genome was sequenced at [[The Institute for Genomic Research]] in a collaboration between [[Jonathan Eisen]] and Scott O'Neill. The second ''Wolbachia'' genome to be determined was of strain wBm, which infects ''[[Brugia malayi]]'' nematodes .<ref name="pmid15780005">{{cite journal | vauthors = Foster J, Ganatra M, Kamal I, Ware J, Makarova K, Ivanova N, Bhattacharyya A, Kapatral V, Kumar S, Posfai J, Vincze T, Ingram J, Moran L, Lapidus A, Omelchenko M, Kyrpides N, Ghedin E, Wang S, Goltsman E, Joukov V, Ostrovskaya O, Tsukerman K, Mazur M, Comb D, Koonin E, Slatko B | title = The Wolbachia genome of Brugia malayi: endosymbiont evolution within a human pathogenic nematode | journal = PLOS Biology | volume = 3 | issue = 4 | pages = e121 | date = April 2005 | pmid = 15780005 | pmc = 1069646 | doi = 10.1371/journal.pbio.0030121 | doi-access = free }}</ref>  Since the development and release of high-throughput sequencing technologies in the mid-2000s, the number of published ''Wolbachia'' genomes has grown significantly, driven by both the decreased cost of sequencing and the expanding interest in studying this bacterium.

The genetic background to the reproductive parasitism has been extensively studied in different host systems. A key factor for the alteration of host reproduction is the presence of the bacteriophage WO<ref>{{Cite journal |last=Masui |first=Shinji |last2=Kamoda |first2=Satoru |last3=Sasaki |first3=Tetsuhiko |last4=Ishikawa |first4=Hajime |date=2000-11-01 |title=Distribution and Evolution of Bacteriophage WO in Wolbachia, the Endosymbiont Causing Sexual Alterations in Arthropods |url=https://link.springer.com/article/10.1007/s002390010112 |journal=Journal of Molecular Evolution |language=en |volume=51 |issue=5 |pages=491–497 |doi=10.1007/s002390010112 |issn=1432-1432}}</ref>, which harbours the CI inducing genes ''cifA'' and ''cifB,'' contributing to the phenotypic expression of altered reproductive success observed in infected hosts<ref>{{Cite journal |last=LePage |first=Daniel P. |last2=Metcalf |first2=Jason A. |last3=Bordenstein |first3=Sarah R. |last4=On |first4=Jungmin |last5=Perlmutter |first5=Jessamyn I. |last6=Shropshire |first6=J. Dylan |last7=Layton |first7=Emily M. |last8=Funkhouser-Jones |first8=Lisa J. |last9=Beckmann |first9=John F. |last10=Bordenstein |first10=Seth R. |date=2017-03 |title=Prophage WO genes recapitulate and enhance Wolbachia-induced cytoplasmic incompatibility |url=https://www.nature.com/articles/nature21391 |journal=Nature |language=en |volume=543 |issue=7644 |pages=243–247 |doi=10.1038/nature21391 |issn=0028-0836 |pmc=PMC5358093 |pmid=28241146}}</ref><ref>{{Cite journal |last=Beckmann |first=John F. |last2=Ronau |first2=Judith A. |last3=Hochstrasser |first3=Mark |date=2017-03-01 |title=A Wolbachia deubiquitylating enzyme induces cytoplasmic incompatibility |url=https://www.nature.com/articles/nmicrobiol20177 |journal=Nature Microbiology |language=en |volume=2 |issue=5 |doi=10.1038/nmicrobiol.2017.7 |issn=2058-5276 |pmc=PMC5336136 |pmid=28248294}}</ref>. 
<!-- TODO: whatever is going on with the hundreds if not thousands of genomes we have on GTDB and the dozens of automatic species -->

=== Horizontal gene transfer ===
Comparative sequence analyses of bacteriophage WO<ref>{{cite journal |vauthors=Masui S, Kamoda S, Sasaki T, Ishikawa H |date=November 2000 |title=Distribution and evolution of bacteriophage WO in Wolbachia, the endosymbiont causing sexual alterations in arthropods |journal=Journal of Molecular Evolution |volume=51 |issue=5 |pages=491–497 |bibcode=2000JMolE..51..491M |doi=10.1007/s002390010112 |pmid=11080372 |s2cid=13558219}}</ref>  offer some of the most compelling examples of large-scale horizontal gene transfer between ''Wolbachia'' coinfections in the same host.<ref name="Kent2011">{{cite journal | vauthors = Kent BN, Salichos L, Gibbons JG, Rokas A, Newton IL, Clark ME, Bordenstein SR | title = Complete bacteriophage transfer in a bacterial endosymbiont (Wolbachia) determined by targeted genome capture | journal = Genome Biology and Evolution | volume = 3 | pages = 209–218 | year = 2011 | pmid = 21292630 | pmc = 3068000 | doi = 10.1093/gbe/evr007 }}</ref> It is the first bacteriophage implicated in frequent lateral transfer between the genomes of bacterial [[endosymbionts]]. Gene transfer by bacteriophages could drive significant evolutionary change in the genomes of intracellular bacteria that were previously considered highly stable or prone to loss of genes over time.<ref name="Kent2011" />

''Wolbachia'' also transfers genes to the host. A nearly complete copy of the ''Wolbachia'' genome sequence was found within the genome sequence of the fruit fly ''[[Drosophila ananassae]]'' and large segments were found in seven other ''Drosophila'' species.<ref>{{cite journal | vauthors = Dunning Hotopp JC, Clark ME, Oliveira DC, Foster JM, Fischer P, Muñoz Torres MC, Giebel JD, Kumar N, Ishmael N, Wang S, Ingram J, Nene RV, Shepard J, Tomkins J, Richards S, Spiro DJ, Ghedin E, Slatko BE, Tettelin H, Werren JH | title = Widespread lateral gene transfer from intracellular bacteria to multicellular eukaryotes | journal = Science | volume = 317 | issue = 5845 | pages = 1753–1756 | date = September 2007 | pmid = 17761848 | doi = 10.1126/science.1142490 | s2cid = 10787254 | citeseerx = 10.1.1.395.1320 | bibcode = 2007Sci...317.1753H }}</ref>

In an application of [[DNA barcoding]] to the identification of species of ''[[Protocalliphora]]'' flies, several distinct morphospecies had identical cytochrome c oxidase I gene sequences, most likely through [[horizontal gene transfer]] (HGT) by ''Wolbachia'' species as they jump across host species.<ref name = "Whitworthetal">{{cite journal | vauthors = Whitworth TL, Dawson RD, Magalon H, Baudry E | title = DNA barcoding cannot reliably identify species of the blowfly genus Protocalliphora (Diptera: Calliphoridae) | journal = Proceedings. Biological Sciences | volume = 274 | issue = 1619 | pages = 1731–1739 | date = July 2007 | pmid = 17472911 | pmc = 2493573 | doi = 10.1098/rspb.2007.0062 }}</ref> As a result, ''Wolbachia'' can cause misleading results in [[molecular phylogeny|molecular]] [[cladistics|cladistical]] analyses.<ref>{{Cite journal | vauthors = Johnstone RA, Hurst GD |year=1996 |title=Maternally inherited male-killing microorganisms may confound interpretation of mitochondrial DNA variability |journal=[[Biological Journal of the Linnean Society]] |volume=58 |issue=4 |pages=453–470 |doi=10.1111/j.1095-8312.1996.tb01446.x|doi-access=free }}</ref> It is estimated that between 20 and 50 percent of insect species have evidence of HGT from ''Wolbachia''—passing from microbes to animal (i.e. insects).<ref>{{Cite book|title=I contain multitudes : the microbes within us and a grander view of life| vauthors = Yong E |isbn=978-0-06-236859-1|edition=First U.S.|location=New York, NY|pages=197|oclc=925497449|date = 2016-08-09}}</ref>

== Small RNA ==
The small [[non-coding RNA]]s '''WsnRNA-46''' and '''WsnRNA-59''' in ''Wolbachia'' were detected in ''[[Aedes aegypti]]'' mosquitoes and ''Drosophila melanogaster''. The [[small RNA]]s (sRNAs) may regulate bacterial and host genes.<ref>{{cite journal | vauthors = Mayoral JG, Hussain M, Joubert DA, Iturbe-Ormaetxe I, O'Neill SL, Asgari S | title = Wolbachia small noncoding RNAs and their role in cross-kingdom communications | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 111 | issue = 52 | pages = 18721–18726 | date = December 2014 | pmid = 25512495 | pmc = 4284532 | doi = 10.1073/pnas.1420131112 | doi-access = free | bibcode = 2014PNAS..11118721M }}</ref> Highly conserved intragenic region sRNA called '''ncrwmel02''' was also identified in ''Wolbachia pipientis.'' It is expressed in four different strains in a regulated pattern that differs according to the sex of the host and the tissue localisation. This suggested that the sRNA may play important roles in the biology of ''Wolbachia.''<ref>{{cite journal | vauthors = Woolfit M, Algama M, Keith JM, McGraw EA, Popovici J | title = Discovery of putative small non-coding RNAs from the obligate intracellular bacterium Wolbachia pipientis | journal = PLOS ONE | volume = 10 | issue = 3 | pages = e0118595 | date = 2015-01-01 | pmid = 25739023 | pmc = 4349823 | doi = 10.1371/journal.pone.0118595 | doi-access = free | bibcode = 2015PLoSO..1018595W }}</ref>

==Relation to human-related infections==

===Role in parasites===
Outside of insects, ''Wolbachia'' infects a variety of [[isopod]] species, [[spider]]s, [[mite]]s, and many species of filarial [[nematode]]s (a type of [[parasitic worm]]), including those causing [[onchocerciasis]] (river blindness) and [[elephantiasis tropica|elephantiasis]] in humans, as well as [[heartworm]]s in dogs. Not only are these disease-causing filarial worms infected with ''Wolbachia'', but ''Wolbachia'' also seems to play an inordinate role in these diseases.

A large part of the pathogenicity of filarial nematodes is due to host immune response toward their ''Wolbachia''. Elimination of ''Wolbachia'' from filarial nematodes generally results in either death or sterility of the nematode.<ref name="pmid12684759">{{cite journal | vauthors = Hoerauf A, Mand S, Fischer K, Kruppa T, Marfo-Debrekyei Y, Debrah AY, Pfarr KM, Adjei O, Büttner DW | title = Doxycycline as a novel strategy against bancroftian filariasis-depletion of Wolbachia endosymbionts from Wuchereria bancrofti and stop of microfilaria production | journal = Medical Microbiology and Immunology | volume = 192 | issue = 4 | pages = 211–216 | date = November 2003 | pmid = 12684759 | doi = 10.1007/s00430-002-0174-6 | s2cid = 23349595 }}</ref> Consequently, current strategies for control of filarial nematode diseases include elimination of their symbiotic ''Wolbachia'' via the simple [[doxycycline]] antibiotic, rather than directly killing the nematode with often more toxic antinematode medications.<ref name="pmid15964448">{{cite journal | vauthors = Taylor MJ, Makunde WH, McGarry HF, Turner JD, Mand S, Hoerauf A | title = Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial | journal = Lancet | volume = 365 | issue = 9477 | pages = 2116–2121 | year = 2005 | pmid = 15964448 | doi = 10.1016/S0140-6736(05)66591-9 | s2cid = 21382828 }}</ref>

=== Disease prevention ===
{{Further|Biological pest control}}
[[File:Mohamad Nasir Wolbachia mosquito lab visit.jpg|thumb|Indonesian research minister [[Mohamad Nasir]] during a visit to a ''Wolbachia'' mosquito lab of the Eliminate Dengue Project.]]

Naturally existing strains of ''Wolbachia'' have been shown to be a route for [[vector control]] strategies because of their presence in arthropod populations, such as mosquitoes.<ref>{{cite journal | vauthors = Xi Z, Dean JL, Khoo C, Dobson SL | title = Generation of a novel Wolbachia infection in Aedes albopictus (Asian tiger mosquito) via embryonic microinjection | journal = Insect Biochemistry and Molecular Biology | volume = 35 | issue = 8 | pages = 903–910 | date = August 2005 | pmid = 15944085 | pmc = 1410910 | doi = 10.1016/j.ibmb.2005.03.015 | bibcode = 2005IBMB...35..903X }}</ref><ref>{{cite journal | vauthors = Moreira LA, Iturbe-Ormaetxe I, Jeffery JA, Lu G, Pyke AT, Hedges LM, Rocha BC, Hall-Mendelin S, Day A, Riegler M, Hugo LE, Johnson KN, Kay BH, McGraw EA, van den Hurk AF, Ryan PA, O'Neill SL | title = A Wolbachia symbiont in Aedes aegypti limits infection with dengue, Chikungunya, and Plasmodium | journal = Cell | volume = 139 | issue = 7 | pages = 1268–1278 | date = December 2009 | pmid = 20064373 | doi = 10.1016/j.cell.2009.11.042 | s2cid = 2018937 | doi-access = free }}</ref> Due to the unique traits of ''Wolbachia'' that cause [[cytoplasmic incompatibility]], some strains are useful to humans as a promoter of genetic drive within an insect population. ''Wolbachia''-infected females are able to produce offspring with uninfected and infected males; however, uninfected females are only able to produce viable offspring with uninfected males. This gives infected females a reproductive advantage that is greater the higher the frequency of ''Wolbachia'' in the population. Computational models predict that introducing ''Wolbachia'' strains into natural populations will reduce pathogen transmission and reduce overall disease burden.<ref>{{cite journal | vauthors = Hancock PA, Sinkins SP, Godfray HC | title = Strategies for introducing Wolbachia to reduce transmission of mosquito-borne diseases | journal = PLOS Neglected Tropical Diseases | volume = 5 | issue = 4 | pages = e1024 | date = April 2011 | pmid = 21541357 | pmc = 3082501 | doi = 10.1371/journal.pntd.0001024 | doi-access = free }}</ref> An example includes a life-shortening ''Wolbachia'' that can be used to control [[Dengue fever|dengue]] virus and [[malaria]] by eliminating the older insects that contain more parasites. Promoting the survival and reproduction of younger insects lessens selection pressure for evolution of resistance.<ref>{{cite journal | vauthors = McMeniman CJ, Lane RV, Cass BN, Fong AW, Sidhu M, Wang YF, O'Neill SL | title = Stable introduction of a life-shortening Wolbachia infection into the mosquito Aedes aegypti | journal = Science | volume = 323 | issue = 5910 | pages = 141–144 | date = January 2009 | pmid = 19119237 | doi = 10.1126/science.1165326 | s2cid = 12641881 | bibcode = 2009Sci...323..141M }}</ref><ref>{{cite news|title='Bug' could combat dengue fever|url=http://news.bbc.co.uk/1/hi/health/7804326.stm|date=2 January 2009|work=BBC News|publisher=British Broadcasting Corporation}}</ref>

[[File:Adi Utarini VOA.jpg|thumb|[[Adi Utarini]], research lead of the ''Wolbachia'' trial in [[Yogyakarta]], Indonesia]]
<!-- non-lifecycle effects: direct antiviral/antipathogenic -->
In addition, some ''Wolbachia'' strains are able to directly reduce viral replication inside the insect. For dengue they include wAllbB and wMelPop with ''[[Aedes aegypti]]'', wMel with ''[[Aedes albopictus]]''<ref>{{cite journal | vauthors = Blagrove MS, Arias-Goeta C, Failloux AB, Sinkins SP | title = Wolbachia strain wMel induces cytoplasmic incompatibility and blocks dengue transmission in Aedes albopictus | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 1 | pages = 255–260 | date = January 2012 | pmid = 22123944 | pmc = 3252941 | doi = 10.1073/pnas.1112021108 | doi-access = free | bibcode = 2012PNAS..109..255B }}</ref> and ''[[Aedes aegypti]]''.<ref>{{cite journal | vauthors = Hoffmann AA, Iturbe-Ormaetxe I, Callahan AG, Phillips BL, Billington K, Axford JK, Montgomery B, Turley AP, O'Neill SL | title = Stability of the wMel Wolbachia Infection following invasion into Aedes aegypti populations | journal = PLOS Neglected Tropical Diseases | volume = 8 | issue = 9 | pages = e3115 | date = September 2014 | pmid = 25211492 | pmc = 4161343 | doi = 10.1371/journal.pntd.0003115 | doi-access = free }}</ref>

''Wolbachia'' has also been identified to inhibit replication of chikungunya virus (CHIKV) in ''A. aegypti''. The ''w''Mel strain of ''Wolbachia pipientis'' significantly reduced infection and dissemination rates of CHIKV in mosquitoes, compared to ''Wolbachia'' uninfected controls and the same phenomenon was observed in yellow fever virus infection converting this bacterium in an excellent promise for YFV and CHIKV suppression.<ref>{{cite journal | vauthors = van den Hurk AF, Hall-Mendelin S, Pyke AT, Frentiu FD, McElroy K, Day A, Higgs S, O'Neill SL | title = Impact of Wolbachia on infection with chikungunya and yellow fever viruses in the mosquito vector Aedes aegypti | journal = PLOS Neglected Tropical Diseases | volume = 6 | issue = 11 | pages = e1892 | year = 2012 | pmid = 23133693 | pmc = 3486898 | doi = 10.1371/journal.pntd.0001892 | doi-access = free }}</ref>

''Wolbachia'' also inhibits the secretion of West Nile virus (WNV) in cell line Aag2 derived from ''A. aegypti'' cells. The mechanism is somewhat novel, as the bacteria actually enhances the production of viral genomic RNA in the cell line ''Wolbachia''. Also, the antiviral effect in intrathoracically infected mosquitoes depends on the strain of ''Wolbachia'', and the replication of the virus in orally fed mosquitoes was completely inhibited in wMelPop strain of ''Wolbachia''.<ref>{{cite journal | vauthors = Hussain M, Lu G, Torres S, Edmonds JH, Kay BH, Khromykh AA, Asgari S | title = Effect of Wolbachia on replication of West Nile virus in a mosquito cell line and adult mosquitoes | journal = Journal of Virology | volume = 87 | issue = 2 | pages = 851–858 | date = January 2013 | pmid = 23115298 | pmc = 3554047 | doi = 10.1128/JVI.01837-12 }}</ref>

The effect of ''Wolbachia'' infection on virus replication in insect hosts is complex and depends on the ''Wolbachia'' strain and virus species.<ref name="pmid26556361">{{cite journal | vauthors = Johnson KN | title = The Impact of Wolbachia on Virus Infection in Mosquitoes | journal = Viruses | volume = 7 | issue = 11 | pages = 5705–5717 | date = November 2015 | pmid = 26556361 | pmc = 4664976 | doi = 10.3390/v7112903 | doi-access = free }}</ref> While several studies have indicated consistent refractory phenotypes of ''Wolbachia'' infection on positive-sense RNA viruses in ''Drosophila melanogaster'',<ref name="pmid18974344">{{cite journal | vauthors = Hedges LM, Brownlie JC, O'Neill SL, Johnson KN | title = Wolbachia and virus protection in insects | journal = Science | volume = 322 | issue = 5902 | pages = 702 | date = October 2008 | pmid = 18974344 | pmc =  | doi = 10.1126/science.1162418 | s2cid = 206514799 | bibcode = 2008Sci...322..702H }}</ref><ref name="pmid19222304">{{cite journal | vauthors = Teixeira L, Ferreira A, Ashburner M | title = The bacterial symbiont Wolbachia induces resistance to RNA viral infections in Drosophila melanogaster | journal = PLOS Biology | volume = 6 | issue = 12 | pages = e2 | date = December 2008 | pmid = 19222304 | pmc = 2605931 | doi = 10.1371/journal.pbio.1000002 | doi-access = free }}</ref> the yellow fever mosquito ''Aedes aegypti''<ref name="pmid20064373">{{cite journal | vauthors = Moreira LA, Iturbe-Ormaetxe I, Jeffery JA, Lu G, Pyke AT, Hedges LM, Rocha BC, Hall-Mendelin S, Day A, Riegler M, Hugo LE, Johnson KN, Kay BH, McGraw EA, van den Hurk AF, Ryan PA, O'Neill SL | title = A Wolbachia symbiont in Aedes aegypti limits infection with dengue, Chikungunya, and Plasmodium | journal = Cell | volume = 139 | issue = 7 | pages = 1268–1278 | date = December 2009 | pmid = 20064373 | pmc =  | doi = 10.1016/j.cell.2009.11.042 | s2cid = 2018937 | doi-access = free }}</ref> and the Asian tiger mosquito ''Aedes albopictus'',<ref name="pmid25923352">{{cite journal | vauthors = Raquin V, Valiente Moro C, Saucereau Y, Tran FH, Potier P, Mavingui P | title = Native Wolbachia from Aedes albopictus Blocks Chikungunya Virus Infection In Cellulo | journal = PLOS ONE | volume = 10 | issue = 4 | pages = e0125066 | year = 2015 | pmid = 25923352 | pmc = 4414612 | doi = 10.1371/journal.pone.0125066 | doi-access = free | bibcode = 2015PLoSO..1025066R }}</ref><ref name="pmid31846415">{{cite journal | vauthors = Bishop C, Parry R, Asgari S | title = Effect of ''Wolbachia w''AlbB on a positive-sense RNA negev-like virus: a novel virus persistently infecting ''Aedes albopictus'' mosquitoes and cells | journal = The Journal of General Virology | volume = 101 | issue = 2 | pages = 216–225 | date = February 2020 | pmid = 31846415 | pmc =  | doi = 10.1099/jgv.0.001361 | doi-access = free }}</ref> this effect is not seen in DNA virus infection<ref name="pmid19222304"/> and in some cases ''Wolbachia'' infection has been associated or shown to increase single stranded DNA<ref name="pmid30583288">{{cite journal | vauthors = Parry R, Bishop C, De Hayr L, Asgari S | title = Density-dependent enhanced replication of a densovirus in Wolbachia-infected Aedes cells is associated with production of piRNAs and higher virus-derived siRNAs | journal = Virology | volume = 528 | issue =  | pages = 89–100 | date = February 2019 | pmid = 30583288 | pmc =  | doi = 10.1016/j.virol.2018.12.006 | s2cid = 58572380 | doi-access = free }}</ref> and double-stranded DNA virus infection.<ref name="pmid22731846">{{cite journal | vauthors = Graham RI, Grzywacz D, Mushobozi WL, Wilson K | title = Wolbachia in a major African crop pest increases susceptibility to viral disease rather than protects | journal = Ecology Letters | volume = 15 | issue = 9 | pages = 993–1000 | date = September 2012 | pmid = 22731846 | pmc =  | doi = 10.1111/j.1461-0248.2012.01820.x | bibcode = 2012EcolL..15..993G | s2cid = 18513535 | url = http://gala.gre.ac.uk/id/eprint/8744/1/8744_GRZYWACZ_Wolbachia_in_a_Major_African_Crop_Pest_2012.pdf }}</ref> There is also currently no evidence that ''Wolbachia'' infection restricts any tested negative-sense RNA viruses<ref name="pmid29950416">{{cite journal | vauthors = Parry R, Asgari S | title = Aedes Anphevirus: an Insect-Specific Virus Distributed Worldwide in Aedes aegypti Mosquitoes That Has Complex Interplays with Wolbachia and Dengue Virus Infection in Cells | journal = Journal of Virology | volume = 92 | issue = 17 | date = September 2018 | pmid = 29950416 | pmc = 6096813 | doi = 10.1128/JVI.00224-18 }}</ref><ref name="pmid29789369">{{cite journal | vauthors = Schultz MJ, Tan AL, Gray CN, Isern S, Michael SF, Frydman HM, Connor JH | title = ''Wolbachia w''Stri Blocks Zika Virus Growth at Two Independent Stages of Viral Replication | journal = mBio | volume = 9 | issue = 3 | date = May 2018 | pmid = 29789369 | pmc = 5964347 | doi = 10.1128/mBio.00738-18 }}</ref><ref name="pmid29084217">{{cite journal | vauthors = Dodson BL, Andrews ES, Turell MJ, Rasgon JL | title = Wolbachia effects on Rift Valley fever virus infection in Culex tarsalis mosquitoes | journal = PLOS Neglected Tropical Diseases | volume = 11 | issue = 10 | pages = e0006050 | date = October 2017 | pmid = 29084217 | pmc = 5693443 | doi = 10.1371/journal.pntd.0006050 | doi-access = free }}</ref><ref name="pmid34492433">{{cite journal | vauthors = Parry R, de Malmanche H, Asgari S | title = Persistent Spodoptera frugiperda rhabdovirus infection in Sf9 cells is not restricted by Wolbachia wMelPop-CLA and wAlbB strains and is targeted by the RNAi machinery | journal = Virology | volume = 563 | issue =  | pages = 82–87 | date = November 2021 | pmid = 34492433 | pmc =  | doi = 10.1016/j.virol.2021.08.013 | s2cid = 237442034 | doi-access = free }}</ref> indicating ''Wolbachia'' would be unsuitable for restriction of negative-sense RNA arthropod borne viruses.

''Wolbachia'' infection can also increase mosquito resistance to malaria, as shown in ''[[Anopheles stephensi]]'' where the ''w''AlbB strain of ''Wolbachia'' hindered the lifecycle of ''[[Plasmodium falciparum]]''.<ref>{{cite journal | vauthors = Bian G, Joshi D, Dong Y, Lu P, Zhou G, Pan X, Xu Y, Dimopoulos G, Xi Z | title = Wolbachia invades Anopheles stephensi populations and induces refractoriness to Plasmodium infection | journal = Science | volume = 340 | issue = 6133 | pages = 748–751 | date = May 2013 | pmid = 23661760 | doi = 10.1126/science.1236192 | s2cid = 206548292 | bibcode = 2013Sci...340..748B }}</ref>

However, ''Wolbachia'' infections can also enhance pathogen transmission. ''Wolbachia'' has enhanced multiple [[arbovirus]]es in ''[[Culex tarsalis]]'' mosquitoes.<ref>{{cite web | vauthors = Rasgon JL |date=2017 |title=Wolbachia-induced enhancement of human arboviral pathogens |url=https://pennstate.pure.elsevier.com/en/projects/wolbachia-induced-enhancement-of-human-arboviral-pathogens |website=Penn State |access-date=5 May 2020}}</ref> In another study, West Nile virus (WNV) infection rate was significantly higher in ''Wolbachia'' (strain wAlbB)-infected ''C. tarsalis'' compared to controls.<ref name="MyUser_Https:_May_5_2020c">{{cite journal | vauthors = Dodson BL, Hughes GL, Paul O, Matacchiero AC, Kramer LD, Rasgon JL | title = Wolbachia enhances West Nile virus (WNV) infection in the mosquito Culex tarsalis | journal = PLOS Neglected Tropical Diseases | volume = 8 | issue = 7 | pages = e2965 | date = July 2014 | pmid = 25010200 | pmc = 4091933 | doi = 10.1371/journal.pntd.0002965 | doi-access = free }}</ref>
 
<!-- Previous part: Mech. of action -->
''Wolbachia'' may induce [[reactive oxygen species]]–dependent activation of the [[Toll (gene family)]] pathway, which is essential for activation of antimicrobial [[peptide]]s, [[defensin]]s, and [[cecropin]]s that help to inhibit virus proliferation.<ref>{{cite journal | vauthors = Pan X, Zhou G, Wu J, Bian G, Lu P, Raikhel AS, Xi Z | title = Wolbachia induces reactive oxygen species (ROS)-dependent activation of the Toll pathway to control dengue virus in the mosquito Aedes aegypti | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 1 | pages = E23–E31 | date = January 2012 | pmid = 22123956 | pmc = 3252928 | doi = 10.1073/pnas.1116932108 | doi-access = free | bibcode = 2012PNAS..109E..23P }}</ref> Conversely, certain strains actually dampen the pathway, leading to higher replication of viruses. One example is with strain wAlbB in ''Culex tarsalis'', where infected mosquitoes actually carried the West Nile virus (WNV) more frequently. This is because wAlbB inhibits REL1, an activator of the antiviral Toll immune pathway. As a result, careful studies of the ''Wolbachia'' strain and ecological consequences must be done before releasing artificially-infected mosquitoes in the environment.<ref name="MyUser_Https:_May_5_2020c"/>

==== Techniques and deployments ====

===== Strain wMel, mixed-sex =====
The World Mosquito Program (WMP) uses ''Wolbachia'' strain wMel to infect ''Aedes'' mosquitos. The mixed-sex mosquitos are intended to infect the local population with wMel, giving them transmission resistance.<ref>{{cite web |title=Our Wolbachia method |url=https://www.worldmosquitoprogram.org/en/work/wolbachia-method |website=World Mosquito Program |language=en}}</ref>

In 2014, WMP released infected mosquitos in [[Townsville]], an Australia city with 187,000 inhabitants plagued by dengue. For four years after introduction, no cases of dengue were reported.<ref>{{cite journal |last1=O'Neill |first1=SL |last2=Ryan |first2=PA |last3=Turley |first3=AP |last4=Wilson |first4=G |last5=Retzki |first5=K |last6=Iturbe-Ormaetxe |first6=I |last7=Dong |first7=Y |last8=Kenny |first8=N |last9=Paton |first9=CJ |last10=Ritchie |first10=SA |last11=Brown-Kenyon |first11=J |last12=Stanford |first12=D |last13=Wittmeier |first13=N |last14=Jewell |first14=NP |last15=Tanamas |first15=SK |last16=Anders |first16=KL |last17=Simmons |first17=CP |title=Scaled deployment of Wolbachia to protect the community from dengue and other Aedes transmitted arboviruses. |journal=Gates Open Research |date=2018 |volume=2 |pages=36 |doi=10.12688/gatesopenres.12844.3 |pmid=30596205 |pmc=6305154 |doi-access=free }}</ref> Trials in much smaller areas had been carried out, but a larger area had not been tested. No environmental ill-effects were reported. The cost was [[A$]]15 per inhabitant, but it was hoped that it could be reduced to [[US$]]1 in poorer countries with lower labor costs.<ref>{{Cite news |url=https://www.theguardian.com/society/2018/aug/01/dengue-fever-outbreak-halted-by-release-of-infected-mosquitoes |title=Dengue fever outbreak halted by release of special mosquitoes |newspaper=The Guardian| vauthors = Boseley S |date= 1 August 2018}}</ref>

In 2016, WMP scientist Scott Ritchie proposed using wMel mosquitos to combat the spread of the [[Zika virus]].<ref>{{cite news|url=https://www.bloomberg.com/news/articles/2016-02-04/as-zika-virus-goes-global-scientists-breed-infected-mosquitoes|title=The Best Weapon for Fighting Zika? More Mosquitoes| vauthors = Gale J |date=4 February 2016|work=Bloomberg.com}}</ref> A study reported that ''Wolbachia'' wMel has the ability to block Zika in Brazil.<ref>{{cite journal | vauthors = Dutra HL, Rocha MN, Dias FB, Mansur SB, Caragata EP, Moreira LA | title = Wolbachia Blocks Currently Circulating Zika Virus Isolates in Brazilian Aedes aegypti Mosquitoes | journal = Cell Host & Microbe | volume = 19 | issue = 6 | pages = 771–774 | date = June 2016 | pmid = 27156023 | pmc = 4906366 | doi = 10.1016/j.chom.2016.04.021 }}</ref> In October 2016, it was announced that US$18 million in funding was being allocated for the use of ''Wolbachia''-infected mosquitoes to fight Zika and dengue viruses. Deployment was slated for early 2017 in Colombia and Brazil.<ref>{{cite web | vauthors = Schnirring L | work = CIDRAP News  | date = 26 October 2016 |url=http://www.cidrap.umn.edu/news-perspective/2016/10/wolbachia-efforts-ramp-fight-zika-brazil-colombia|title=Wolbachia efforts ramp up to fight Zika in Brazil, Colombia}}</ref>

Between 2016 and 2020, WMP conducted its first [[randomized controlled trial]] in [[Yogyakarta]], an Indonesian city of about 400,000 inhabitants. In August 2020, the trial's Indonesian lead scientist [[Adi Utarini]] announced that the trial showed a 77% reduction in dengue cases compared to the control areas. This trial was the "strongest evidence yet" for the technique.<ref name="yogya nature">{{cite journal | vauthors = Callaway E | title = The mosquito strategy that could eliminate dengue | journal = Nature | date = August 2020 | pmid = 32855552 | doi = 10.1038/d41586-020-02492-1 | s2cid = 221359975 }}</ref><ref name=nature10>{{Cite web|title=Nature's 10: ten people who helped shape science in 2020|date=15 December 2020 |url=https://www.nature.com/articles/d41586-020-03435-6|access-date=2020-12-19 |language=en}}</ref>

In 2017&ndash;2019, WMP released mosquitos in Niterói, Brazil.<ref>{{cite journal |last1=Pinto |first1=SB |last2=Riback |first2=TIS |last3=Sylvestre |first3=G |last4=Costa |first4=G |last5=Peixoto |first5=J |last6=Dias |first6=FBS |last7=Tanamas |first7=SK |last8=Simmons |first8=CP |last9=Dufault |first9=SM |last10=Ryan |first10=PA |last11=O'Neill |first11=SL |last12=Muzzi |first12=FC |last13=Kutcher |first13=S |last14=Montgomery |first14=J |last15=Green |first15=BR |last16=Smithyman |first16=R |last17=Eppinghaus |first17=A |last18=Saraceni |first18=V |last19=Durovni |first19=B |last20=Anders |first20=KL |last21=Moreira |first21=LA |title=Effectiveness of Wolbachia-infected mosquito deployments in reducing the incidence of dengue and other Aedes-borne diseases in Niterói, Brazil: A quasi-experimental study. |journal=PLOS Neglected Tropical Diseases |date=July 2021 |volume=15 |issue=7 |pages=e0009556 |doi=10.1371/journal.pntd.0009556 |pmid=34252106 |pmc=8297942 |doi-access=free }}</ref>

In March 2023, Brazil's [[Oswaldo Cruz Foundation]] signed an agreement with WMP to provide funds for a large "mosquito factory" producing infected insects.<ref>{{cite web |title=Brazil to build mosquito factory to fight dengue, Zika, chikungunya |url=https://agenciabrasil.ebc.com.br/en/geral/noticia/2023-03/new-aedes-aegypti-factory-brazil-will-expand-fight-against-diseases |website=Agência Brasil |language=en |date=31 March 2023}}</ref>

===== Male incompatibility =====
Another method to use ''Wolbachia'' in mosquitos exploits the cytoplamic incompatibility between infected males and uninfected females. If an uninfected female mates with an infected male, her eggs become infertile. With enough infected males released, the mosquito population would be reduced temporarily.<ref name=ver/>

[[Verily]], the life sciences arm of Google's parent company [[Alphabet Inc.]], uses this method. In July 2017, it announced a plan to release about 20 million ''Wolbachia''-infected male ''Aedes aegypti'' mosquitoes in [[Fresno]], [[California]], in an attempt to combat the [[Zika]] virus.<ref name=ver>{{cite web| vauthors = Buhr S |title=Google's life sciences unit is releasing 20 million bacteria-infected mosquitoes in Fresno|url=https://techcrunch.com/2017/07/14/googles-life-sciences-unit-is-releasing-20-million-bacteria-infected-mosquitoes-in-fresno/|website=TechCrunch|date=14 July 2017 |publisher=Oath Inc.|access-date=14 July 2017}}</ref><ref>{{cite web| vauthors = Mullin E |title=Verily Robot Will Raise 20 Million Sterile Mosquitoes for Release in California|url=https://www.technologyreview.com/s/608280/alphabet-has-built-a-robot-that-is-releasing-millions-of-sterile-mosquitoes-in-california/|website=MIT Technology Review|access-date=17 July 2017}}</ref> Singapore's National Environment Agency has teamed up with Verily to come up with an advanced, more efficient way to release male ''Wolbachia'' mosquitoes for Phase 2 of its study to suppress the urban ''Aedes aegypti'' mosquito population and fight dengue.<ref>{{Cite web | vauthors = Goh C | date = 18 September 2018 |url=https://www.channelnewsasia.com/news/singapore/nea-alphabet-inc-s-verily-team-up-to-fight-dengue-with-ai-10731556 | archive-url = https://web.archive.org/web/20180919121518/https://www.channelnewsasia.com/news/singapore/nea-alphabet-inc-s-verily-team-up-to-fight-dengue-with-ai-10731556 | archive-date = 19 September 2018 |title=NEA, Alphabet Inc's Verily team up to fight dengue with AI|website=Channel NewsAsia|access-date=2019-02-02}}</ref>

On November 3, 2017, the [[US Environmental Protection Agency]] (EPA) registered Mosquito Mate, Inc. to release ''Wolbachia'' strain "ZAP"-infected male mosquitoes in 20 US states and the District of Columbia.<ref>{{cite web|title=EPA Registers the Wolbachia ZAP Strain in Live Male Asian Tiger Mosquitoes | work = U.S. Environmental Protection Agency (EPA) |date=7 November 2017|url=https://www.epa.gov/pesticides/epa-registers-wolbachia-zap-strain-live-male-asian-tiger-mosquitoes/|access-date= 8 November 2017}}</ref>

== See also ==
* [[Intragenomic conflict]]
* [[Quorum sensing]]
* ''[[Delftia tsuruhatensis]]'' a bacterium that naturally prevent malaria.
* ''[[Serratia]]'' a genus of bacteria that can be genetically modified to prevent malaria.

== References ==
{{Reflist}}

== Further reading ==
{{Refbegin}}
* {{cite journal | vauthors = Werren JH | title = Biology of Wolbachia | journal = Annual Review of Entomology | volume = 42 | pages = 587–609 | year = 1997 | pmid = 15012323 | doi = 10.1146/annurev.ento.42.1.587 }}
* {{cite journal | vauthors = Klasson L, Westberg J, Sapountzis P, Näslund K, Lutnaes Y, Darby AC, Veneti Z, Chen L, Braig HR, Garrett R, Bourtzis K, Andersson SG | title = The mosaic genome structure of the Wolbachia wRi strain infecting Drosophila simulans | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 14 | pages = 5725–5730 | date = April 2009 | pmid = 19307581 | pmc = 2659715 | doi = 10.1073/pnas.0810753106 | author12-link = Siv G. E. Andersson | doi-access = free | bibcode = 2009PNAS..106.5725K }}
{{Refend}}

== External links ==
* [http://www.bacteriamuseum.org/species/Wolbachia.shtml Virtual Museum of Bacteria] {{Webarchive|url=https://web.archive.org/web/20080922101708/http://www.bacteriamuseum.org/species/Wolbachia.shtml |date=2008-09-22 }}
* [https://web.archive.org/web/20050615102650/http://wolbachia.sols.uq.edu.au/index.html ''Wolbachia'' research portal] at the [[National Science Foundation]]
* {{cite news|title=One Species' Genome Discovered Inside Another's—Bacterial to Animal Gene Transfers Now Shown to be Widespread, with Implications for Evolution and Control of Diseases and Pests |url=http://www.rochester.edu/news/show.php?id=2963 |date=30 August 2007 |publisher=University of Rochester |access-date=27 November 2007}}
* {{EOL|98247}}
* [https://www.vanderbilt.edu/wolbachiaproject/ The ''Wolbachia Project''] at [[Vanderbilt University]]
* [http://www.pnas.org/content/101/42/15042/F1.large.jpg Images of Wolbachia]

{{Taxonbar|from=Q283526}}
{{Authority control}}

[[Category:Bacteria genera]]
[[Category:Endosymbiotic events]]
[[Category:Gram-negative bacteria]]
[[Category:Rickettsiales]]