Bacterial parasite shows potential in disease control

The recently completed Wolbachia pipientis gene sequence is paving the way to understanding this parasite's interaction with its insect hosts.

Wolbachia may well be the most sexist bacterium in creation. It certainly hates males to death. A member of one of the most diverse group, the proteobacteria, this parasitic endosymbiont lives inside the reproductive cells of a wide variety of the 25 million-strong species of arthropods, including insects, spiders, and crustaceans.

According to Prof Scott O'Neill, head of the school of life sciences at the University of Queensland, Wolbachia's effects range from beneficial to pathological -- the latter, particularly, if the host is male.

"The reason is that Wolbachia pipientis bacteria are transmitted through females," O'Neill says. "To maximise its chances of being passed on from one generation to the next, it has developed specialist strategies to manipulate the reproduction often at the expense of males.

"In some cases it is capable of converting males to females. Its survival is based on its ability to selfishly manipulate the female. As far as Wolbachia are concerned, males are irrelevant."

Interestingly, the Wolbachia infection can be slightly beneficial to some female insect species and somewhat detrimental to others. Having the bacteria increases fecundity in some parasitic wasps. In most other insects, however, there is a slight fitness cost, causing the female to produce fewer eggs.

With their ability to infect millions of invertebrate species, Wolbachia are probably the most widespread symbiotic bacteria on planet Earth.

The biochemical mechanisms that trigger different strategies in different hosts are unclear, in part because so far it has been impossible to grow sufficient quantities of these bacteria outside their host.

But now that O'Neill, together with Dr Jonathan Eisen of The Institute for Genomic Research (TIGR) and colleagues have sequenced the complete genome of one strain of Wolbachia pipientis, scientists are already gaining new insight into the biology and evolution of Wolbachia-host interactions.

Multiple practical applications are being proposed, including using Wolbachia to control insect pests.

In a recent study of nematodes that cause disease in humans, it has been observed that Wolbachia are clearly beneficial to the host. If the worm is treated with antibiotics to remove the bacteria, the nematode's reproductive process is arrested and the worm ultimately dies.

"It might also provide a new approach to the control of human and animal filariasis (diseases such as elephantiasis), since the worms that cause filariasis, river blindness and a range of human and animal diseases require the endosymbiotic Wolbachia for survival," notes O'Neill.

Another potential outcome of this research is to tap into Wolbachia's ability to spread into insect populations, like a Trojan horse, to carry genes into their hosts that may inhibit the transmission of parasites into humans, like malaria and dengue fever.

O'Neill is also studying strains of Wolbachia that actually shorten the host's life span, especially in diseases like dengue and malaria where only the very old mosquitoes are able to infect humans.

"If we can succeed in manipulating the insects' age structure to skew it towards younger individuals it may be possible to eventually eliminate their ability to transmit those disease agents."

Popcorn

Discovered by Seymour Benzer at CalTech while studying the biology of ageing, this type of Wolbachia, nicknamed 'popcorn' because of the appearance of the accumulated bacteria in the Drosophilae fly brain, selectively kills old insects.

The long-term potential of the Wolbachiaresearch could lead to the development of strategies to eliminate or at least control some devastating insect transmitted diseases.

An undergraduate of University of Sydney, O'Neil gained his PhD in entomology at the University of Queensland. After postgraduate work at the University of Illinois he accepted a position on the faculty at Yale University, becoming associate professor and head of the vector biology group studying insect transmitted diseases at Yale Medical School.

Back in Australia, O'Neill is currently working on bacterial symbiosis with a particular interest in Wolbachia, endeavouring to understand the molecular mechanisms that mediate the interactions between the bacteria and the insects.

While still early in the research process, discovering the genome sequence has been a huge step forward, says O'Neill, who began the project while still at Yale University with a grant from the National Institute of Health and New England BioLabs of Boston.

O'Neill's laboratory at Yale did the initial purification and material preparation in collaboration with TIGR's sequencing centre. The genome was then annotated and analysed in collaboration.

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