Open questions: how does Wolbachia do what it does?
© Jiggins. 2016
Published: 19 October 2016
A common symbiont of insects, the bacterium Wolbachia has been implicated in phenomena as diverse as sex determination, pathogen defence and speciation and is being used in public health programs to prevent mosquitoes transmitting disease. Despite decades of research, we know remarkably little about how it exerts its effects.
Thirteen years ago I was frustrated with my research and decided to change direction. I had been working on a bacterial symbiont called Wolbachia that is thought to infect over half of arthropod species—that’s over a million species . As an evolutionary biologist I was fascinated by an organism that manipulated the reproduction of its hosts in bizarre ways to enhance its own transmission. As a geneticist, however, I was left frustrated. The bacterium could not be cultured or manipulated, so despite its being studied by hundreds of researchers, only the most rudimentary details were known about how it exerts its effects. I decided the time had come to move on and study interactions between Drosophila and viruses, so it was much to my surprise when five years later two studies reported that Wolbachia protects Drosophila against RNA viruses [2, 3]. Returning to the field, I found that the importance of Wolbachia in the biology of insects and other arthropods was more apparent than ever. The bacterium has been implicated in phenomena as diverse as speciation , the evolution of sex determination mechanisms  and the synthesis of essential vitamins . Within a few years of its antiviral effects being reported, Wolbachia-infected mosquitoes were being released to prevent the transmission of dengue virus . However, the mechanisms underlying these effects remain poorly understood.
The first description of a phenotypic effect of Wolbachia on its hosts came in 1971, when Yen and Barr  linked the bacterium to a phenomenon known as cytoplasmic incompatibility (CI). Wolbachia is transmitted from infected females to their offspring through eggs and CI allows it to rapidly spread through populations. The bacterium modifies the sperm of infected males during spermatogenesis so that the paternal chromosomes condense when an egg is fertilised, which typically kills the developing embryo . However, if the egg is infected with the same strain of Wolbachia as was found in the male insect, this chromosomal mark is ‘rescued’ and development proceeds normally. At the population level, the selective killing of Wolbachia-free zygotes causes the frequency of infected individuals to increase. Despite detailed descriptions of how CI disrupts the cell cycle and paternal chromosomes , the molecular basis for how paternal chromosomes are marked and then rescued remains unknown. Advances in epigenetics and chromosome biology make this a timely moment to return to this question.
Some 45 years after the seminal work of Yenn and Barr, the interest of the research community in Wolbachia has never been greater. The field has gone from being an esoteric example of evolution to underpinning many aspects of insect biology and even being the basis of a major public health program. This research effort has yielded tantalising glimpses into the mechanisms by which Wolbachia alters the biology of its hosts, but progress has been slow. Critically, the bacterial factors that interact with the host have remained largely elusive. The challenge for the future is to answer these questions in a system where there are few tools for manipulating the bacterium. These limitations can be partly offset by the fact that Wolbachia infects model organisms such as Drosophila and new technologies and ‘omics approaches are easily applied to other species. Progress is likely to yield new insights into insect genetics and evolution. From the perspective of Wolbachia, it will reveal how this symbiont has evolved such a diverse array of phenotypes and whether common pathways underpin apparently disparate traits.
FJ is supported by European Research Council grant 281668, DrosophilaInfection.
FJ wrote this article.
The author declares that he has no competing interests.
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