MicrobiologyBytes

Wolbachia pipientis is a maternally inherited symbiotic bacteria that is widespread among most insects including laboratory stocks of Drosophila melanogaster, as well as filarial nematodes and crustaceans. Wolbachia belong to the Richettsial family responsible for the deadly human diseases such as typhus, Rocky Mountain spotted fever, and Q fever, but themselves are not involved in any known human diseases. Wolbachia are best known for their ability to induce reproductive alterations in hosts such as male killing, feminization, parthenogenesis, and cytoplasmic incompatibility, all of which result in increased number of infected female offspring and thereby helping vertical transfer of Wolbachia. These reproductive alterations may promote speciation in extreme cases. Because of these intriguing properties, Wolbachia have been extensively studied for entomology, agriculture and evolution.

Despite Wolbachia’s unique role in host reproduction and physiology, their underlying cellular mechanisms are yet to be addressed. Studies with electron microscopy have revealed that Wolbachia bacteria are strictly present in vesicular structures in the cytoplasm of host cells. These Wolbachia vesicles are attached to astral microtubules near centrosomes by short electron-dense bridges, and their centrosomal localization is dependent on microtubules but not actin. Wolbachia bacteria are enclosed within three layers of membranes: the outer layer is host origin and two inner layers are bacterial cell wall and bacterial plasma membrane. Since parasitic bacteria and enveloped mammalian viruses often utilize a variety of subcellular organelles such as endoplasmic reticulum and Golgi apparatus during their life cycles, Wolbachia may also be present in a host organelle that can aid the replication and propagation of Wolbachia. Identification of this host organelle is critical for understanding the Wolbachia‘s ability in changing host physiology.

This paper reports that Wolbachia reside in a group of Golgi-related vesicles. This raises an interesting possibility that Wolbachia may mark the unique group of Golgi vesicles linked to membrane biogenesis. The additional finding that localization of Wolbachia vesicles is regulated by genes involved in cell/tissue polarity also provided a surprising new potential activity for these polarity genes in Golgi localization.

Wolbachia Bacteria Reside in Host Golgi-Related Vesicles Whose Position Is Regulated by Polarity Proteins. (2011) PLoS ONE 6(7): e22703. doi:10.1371/journal.pone.0022703
Wolbachia pipientis are intracellular symbiotic bacteria extremely common in various organisms including Drosophila melanogaster, and are known for their ability to induce changes in host reproduction. These bacteria are present in astral microtubule-associated vesicular structures in host cytoplasm, but little is known about the identity of these vesicles. We report here that Wolbachia are restricted only to a group of Golgi-related vesicles concentrated near the site of membrane biogenesis and minus-ends of microtubules. The Wolbachia vesicles were significantly mislocalized in mutant embryos defective in cell/planar polarity genes suggesting that cell/tissue polarity genes are required for apical localization of these Golgi-related vesicles. Furthermore, two of the polarity proteins, Van Gogh/Strabismus and Scribble, appeared to be present in these Golgi-related vesicles. Thus, establishment of polarity may be closely linked to the precise insertion of Golgi vesicles into the new membrane addition site.

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Bacterial associates are ubiquitous among insects, including mosquitoes. Wolbachia are obligate endosymbiotic bacteria that infect numerous insects, many of which are vectors of pathogenic microorganisms. Interest has centered around Wolbachia as a means of reducing arthropod-borne disease due to the capacity of the bacteria to manipulate the reproduction of the insect host, which in turn favors their own transmission.

Recent studies show that Wolbachia can directly cause pathogen interference (PI) in their invertebrate hosts, whereby infected insects are less susceptible to pathogens. Infection with Wolbachia bacteria has been shown to reduce pathogen levels in multiple mosquito species. Anopheles mosquitoes (the obligate vectors of human malaria) are naturally uninfected with Wolbachia, and stable artificial infections have not yet succeeded in this genus; however somatic infections can be established that can be used to assess the effect of Wolbachia infection in Anopheles. Here, we show that infection with two different Wolbachia strains can significantly reduce levels of the human malaria parasite Plasmodium falciparum in Anopheles gambiae. After infection, Wolbachia disseminate throughout the mosquito but are notably absent from the gut and ovaries. The mosquito immune system is first induced in response to Wolbachia infection, but is then suppressed as the infection progresses. The Wolbachia strain wMelPop is highly virulent to Anopheles only after blood feeding. If stable infections can be established in Anopheles, and they act in a similar manner to somatic infections, Wolbachia could potentially be used as part of a strategy to control malaria.

Wolbachia Infections Are Virulent and Inhibit the Human Malaria Parasite Plasmodium Falciparum in Anopheles Gambiae. 2011 PLoS Pathog 7(5): e1002043. doi:10.1371/journal.ppat.1002043
Endosymbiotic Wolbachia bacteria are potent modulators of pathogen infection and transmission in multiple naturally and artificially infected insect species, including important vectors of human pathogens. Anopheles mosquitoes are naturally uninfected with Wolbachia, and stable artificial infections have not yet succeeded in this genus. Recent techniques have enabled establishment of somatic Wolbachia infections in Anopheles. Here, we characterize somatic infections of two diverse Wolbachia strains (wMelPop and wAlbB) in Anopheles gambiae, the major vector of human malaria. After infection, wMelPop disseminates widely in the mosquito, infecting the fat body, head, sensory organs and other tissues but is notably absent from the midgut and ovaries. Wolbachia initially induces the mosquito immune system, coincident with initial clearing of the infection, but then suppresses expression of immune genes, coincident with Wolbachia replication in the mosquito. Both wMelPop and wAlbB significantly inhibit Plasmodium falciparum oocyst levels in the mosquito midgut. Although not virulent in non-bloodfed mosquitoes, wMelPop exhibits a novel phenotype and is extremely virulent for approximately 12–24 hours post-bloodmeal, after which surviving mosquitoes exhibit similar mortality trajectories to control mosquitoes. The data suggest that if stable transinfections act in a similar manner to somatic infections, Wolbachia could potentially be used as part of a strategy to control the Anopheles mosquitoes that transmit malaria.

Wolbachia are a group of bacteria that infect a major proportion of insect species. They are known for intricate manipulations of their host’s reproduction. The most puzzling manipulation is called Cytoplasmic Incompatibility (CI). In males, CI consists of Wolbachia manipulating the sperm in a yet unknown way – this manipulation is called mod (for modification). DNA from modified sperm cannot properly participate in the first embryonic mitosis, except if Wolbachia action in the egg recovers the functionality of the sperm DNA.

Owing to the nature of CI, a female can only successfully mate with an infected male if she is herself infected by an appropriate Wolbachia strain. If such an infected female mates with an uninfected male, there are no defects. Therefore, infected females have a selective advantage over uninfected ones, helping Wolbachia spread. Considering that CI effectively inhibits certain crosses, Wolbachia infection could lead to reproductive isolation or gene flow reduction between host populations with different infection statuses. Therefore, CI in Wolbachia may play an important role in insect speciation. A deeper insight into the mechanism behind Wolbachia-induced CI is likely to further our understanding of host evolutionary dynamics.

A New Model and Method for Understanding Wolbachia-Induced Cytoplasmic Incompatibility. 2011 PLoS ONE 6(5): e19757. doi:10.1371/journal.pone.0019757
Wolbachia are intracellular bacteria transmitted almost exclusively vertically through eggs. In response to this mode of transmission, Wolbachia strategically manipulate their insect hosts’ reproduction. In the most common manipulation type, cytoplasmic incompatibility, infected males can only mate with infected females, but infected females can mate with all males. The mechanism of cytoplasmic incompatibility is unknown; theoretical and empirical findings need to converge to broaden our understanding of this phenomenon. For this purpose, two prominent models have been proposed: the mistiming-model and the lock-key-model. The former states that Wolbachia manipulate sperm of infected males to induce a fatal delay of the male pronucleus during the first embryonic division, but that the bacteria can compensate the delay by slowing down mitosis in fertilized eggs. The latter states that Wolbachia deposit damaging “locks” on sperm DNA of infected males, but can also provide matching “keys” in infected eggs to undo the damage. The lock-key-model, however, needs to assume a large number of locks and keys to explain all existing incompatibility patterns. The mistiming-model requires fewer assumptions but has been contradicted by empirical results. We therefore expand the mistiming-model by one quantitative dimension to create the new, so-called goalkeeper-model. Using a method based on formal logic, we show that both lock-key- and goalkeeper-model are consistent with existing data. Compared to the lock-key-model, however, the goalkeeper-model assumes only two factors and provides an idea of the evolutionary emergence of cytoplasmic incompatibility. Available cytological evidence suggests that the hypothesized second factor of the goalkeeper-model may indeed exist. Finally, we suggest empirical tests that would allow to distinguish between the models. Generalizing our results might prove interesting for the study of the mechanism and evolution of other host-parasite interactions.

Wolbachia pipientis is an intracellular maternally-inherited bacterial symbiont of invertebrates that is very common in insects, including a number of mosquito species. It can manipulate host reproduction in several ways, including cytoplasmic incompatibility, whereby certain crosses are rendered effectively sterile. Females that are uninfected produce infertile eggs when they mate with males that carry Wolbachia, while there is a “rescue” effect in Wolbachia-infected embryos such that infected females can reproduce successfully with any males. Therefore uninfected females suffer a frequency-dependent reproductive disadvantage. Wolbachia is able to rapidly invade populations using this powerful mechanism

Malaria is one of the world’s most devastating diseases, particularly in Africa, and new control strategies are desperately needed. Here we show that the presence of Wolbachia bacteria inhibits the development of a malaria parasite in the most important Anopheles mosquito species of Africa. In addition it shows that the presence of Wolbachia results in the switching on of immune genes that are known to affect development of many species of malaria parasite. When added to the lifespan-shortening effects of this particular strain of Wolbachia, and the general ability of Wolbachia to spread through insect populations, this study provides a stimulus for the development of Wolbachia-based malaria control methods. It also provides new insights into the wide range of effects of Wolbachia in insects.

Wolbachia Stimulates Immune Gene Expression and Inhibits Plasmodium Development in Anopheles gambiae. (2010) PLoS Pathog 6(10): e1001143. doi:10.1371/journal.ppat.1001143
The over-replicating wMelPop strain of the endosymbiont Wolbachia pipientis has recently been shown to be capable of inducing immune upregulation and inhibition of pathogen transmission in Aedes aegypti mosquitoes. In order to examine whether comparable effects would be seen in the malaria vector Anopheles gambiae, transient somatic infections of wMelPop were created by intrathoracic inoculation. Upregulation of six selected immune genes was observed compared to controls, at least two of which (LRIM1 and TEP1) influence the development of malaria parasites. A stably infected An. gambiae cell line also showed increased expression of malaria-related immune genes. Highly significant reductions in Plasmodium infection intensity were observed in the wMelPop-infected cohort, and using gene knockdown, evidence for the role of TEP1 in this phenotype was obtained. Comparing the levels of upregulation in somatic and stably inherited wMelPop infections in Ae. aegypti revealed that levels of upregulation were lower in the somatic infections than in the stably transinfected line; inhibition of development of Brugia filarial nematodes was nevertheless observed in the somatic wMelPop infected females. Thus we consider that the effects observed in An. gambiae are also likely to be more pronounced if stably inherited wMelPop transinfections can be created, and that somatic infections of Wolbachia provide a useful model for examining effects on pathogen development or dissemination. The data are discussed with respect to the comparative effects on malaria vectorial capacity of life shortening and direct inhibition of Plasmodium development that can be produced by Wolbachia.

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Wolbachia is a maternally transmitted intracellular bacterial symbiont of arthropods. The organism is mainly localized in the reproductive tissues of arthropods and it is responsible for the induction of a number of reproductive alterations including feminization, parthenogenesis, male-killing and cytoplasmic incompatibility. Apart from reproductive parasitism, Wolbachia also participates in mutualistic relationships with nematode hosts. The widespread distribution of Wolbachia as well as the manipulation of host’s reproductive system places this symbiont among the most promising targets for disease/pest control.

Wolbachia was first discovered in the gonads of the mosquito Culex pipientis in 1924. Since then, Wolbachia has been detected in many host tissues. Wolbachia has evolved several strategies to ensure vertical transmission through the manipulation of host reproductive system. These strategies include feminization, parthenogenesis, male killing and cytoplasmic incompatibility. All the above phenotypes, commonly referred to as ‘reproductive parasitism’, increase the frequency of infected females in the host population.

Recent research on Wolbachia has grown on many levels, providing interesting insights on various aspects of the microbe’s biology. Although data from fully sequenced genomes of different Wolbachia strains and from experimental studies of host-microbe interactions continue to arise, most of the molecular mechanisms employed by Wolbachia to manipulate the host cytoplasmic machinery and to ensure vertical transmission are yet to be discovered. Apart from the well-established role of Wolbachia in triggering reproductive alterations, a new fascinating aspect is emerging, related to the ecological benefits that the symbiont provides to the host. The mutualistic relationship of Wolbachia strains with disease vectors remains among the top research priorities with new insights having an impact on putative anti-filarial strategies. Intensive research in this field keeps underlining the biological, ecological, and evolutionary significance of Wolbachia. Unravelling the molecular mechanisms underlying the establishment of the symbiosis and the induction of the reproductive phenotypes will promote the development of novel and environment friendly biotechnological strategies using Wolbachia for the control of insect pests and disease vectors.

Wolbachia: more than just a bug in insects genitals. Curr Opin Microbiol. Dec 23 2009

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BBC NEWS

Humans could be protected from dengue fever by infecting the mosquitoes carrying it with a parasite which halves their lifespan. Australian scientists, writing in the journal Science, found that Wolbachia bacteria spread well through laboratory-bred mosquitoes. Only older mosquitoes pass on dengue – so killing them could cut disease. It remains to be seen how well the bacteria would spread outside the laboratory.

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Wolbachia are members of the Rickettsia, a diverse group of intracellular bacteria that comprises bacteria with parasitic, mutualistic and commensal relationships with their hosts. Typical Rickettsia have life cycles that include an invertebrate vector and mammalian host. However, unlike its close relatives, Wolbachia does not routinely infect vertebrates. Wolbachia species have attracted considerable interest in the past decade primarily because of their abundance, fascinating effects on their hosts and their potential in pest and disease vector control (Wolbachia: master manipulators of invertebrate biology. 2008 Nature Reviews Microbiology 6, 741-751).

Wolbachia have small genomes (1-2 Mb) that are within the size range of the other Rickettsia. Until the early 1990s, Wolbachia were considered to be rare, but with the advent of PCR, Wolbachia were found to be widespread and are in fact common in insects and other arthropods, as well as in nematodes. Recent work estimates that over 65% of insect species harbour Wolbachia, making it among the most abundant intracellular bacterial genus so far discovered, infecting over a million insect species alone.

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Together with their widespread distribution, another interesting feature of Wolbachia is the various host manipulations they induce. The effects of Wolbachia infection include: feminization of genetic males; parthenogenetic induction, resulting in the development of unfertilized eggs; the killing of male progeny from infected females; and sperm–egg incompatibility. Each of these reproductive alterations helps the bacterium by enhancing the production of infected female hosts, and this is referred to as reproductive parasitism. Whether Wolbachia have a role in accelerating the evolution of their hosts is a controversial question, but there is good evidence that parthenogenesis-inducing bacteria have led to the evolution of parthenogenetic insect species.

Considerable progress in understanding the biology of Wolbachia has been made in the past ten years. However, important questions still remain, including: how do Wolbachia manipulate host reproduction; how is the abundance and distribution of Wolbachia maintained globally; can Wolbachia be effectively used in disease control; do Wolbachia have important roles in the evolution of their hosts; and do Wolbachia accelerate the rates of speciation in invertebrates and contribute to novel gene acquisition.

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