Life-shortening bacteria vs. dengue mosquitoes

Blogging on Peer-Reviewed ResearchThe mosquito Aedes aegypti sucks the blood of people from all over the tropics, and exchanges it for the virus that causes dengue fever - a disease that afflicts 40 million people every year. The mosquito has proven to be a tough adversary and efforts to drive it from urban settings have generally failed in the long-term. So how do you fight such an accomplished parasite? Simple - use a better parasite. In fact, try the most successful one in the world, a bacterium called Wolbachia.

i-170aedb739e44b0b341775bc57785eee-Lolbachia1.jpgWolbachia's success rests on two traits. First, it targets the most diverse group of animals on the planet, the insects, infecting the majority of species and about one in eight individuals. Second, it spreads like wildfire by using several extremely self-serving strategies, all of which screw over male insects in some way or other. Wolbachia passes from one generation to the next in the eggs of infected females. But without similar access to sperm, males are useless to it and has evolved a number of ways of dealing with that. Sometimes it kills males outright before they're even born; sometimes it turns them into females.

In other subtler cases, it ensures that infected males can only mate successfully with infected females. If they try to breed with uninfected ones, the embryos die at an early stage of development. This strategy is known as "cytoplasmic incompatibility" and while it's still unclear how it works, there's no doubt that it does. It gives infected females (who can mates with any male they like) a competitive advantage over uninfected females, who are restricted to uninfected males. With this upper hand, massive swathes of a given population eventually become Wolbachia-carriers.

Conor McMeniman and colleagues from the University of Queensland have found a way to use that to their advantage. They have found a strain of Wolbachia that can halve the lifespan of the Aedes mosquito and that induces complete cytoplasmic incompatibility. If introduced into a natural population, it should invade with tremendous zest.

Shortening a mosquito's lifespan may seem like a flimsy victory, but McMeniman recognises it as an important one. Only old mosquitoes really pose a threat to human health because it takes about two weeks for an individual to become infectious after it first sucks up a mouthful of infected blood. The virus first need to reproduce in its gut before travelling back to its salivary glands, where it can spread further. Because mozzies are short-lived anyway, most die before they reach that point, which means that any technique that slashes their already limited lifespan will have a huge impact on controlling the diseases they carry.

i-b86d00910a82becf40aaf474675e3f70-Aedes.jpgFinding a strain of Wolbachia that infects the Aedes mosquito wasn't easy. In a cruel twist of fate, the uber-bacterium doesn't naturally infect either of the mosquito groups that carry dengue or malaria, despite being relatively unfussy about its choice of hosts. But that doesn't mean it can't - a study four years ago proved that Wolbachia can infect Aedes aegypti and can spread to an entire laboratory population within a few generations. The race was on to find the right strain.

McMeniman's group found one called wMelPop, which naturally infects the fly Drosophila melanogaster and halves its lifespan. To acclimatise the strain to a new host, the team cultured it in mosquito cells for three years, producing a version with a preference for mosquitoes instead of Drosophila.

Their new wMelPop strain had all the right traits. It successfully infected mosquitoes and was passed down through over 30 generations. Virtually all of the larvae born to infected females carry Wolbachia themselves. And once infected, a female's days are numbered; under realistic conditions (including tropical temperature and humidity, and daily blood meals) Wolbachia halved the normal mosquito lifespan, just as it does in Drosophila. McMeniman even proved that these shortened lives were solely due to the bacteria by showing that the mosquitoes lived to their usual age if they were cured with a dose of antibiotics.

The Wolbachia strain was also clearly causing cytoplasmic incompatibility. When uninfected or cured individuals breed, over 80% of eggs eventually hatch. But when infected males mated with uninfected females, not a single one of 2,500 eggs produced a living larva.

This trinity of nigh-total inheritance, strong cytoplasmic incompatibility and life-shortening power is exactly the combination of traits needed if Wolbachia can be used as a weapon to control wild populations of mosquitoes. Certainly, strains with similar properties spread well enough in other insect species. Even though Wolbachia lowers a female's lifespan, they don't hurt her egg-laying ability, or kill her off before she gets a chance to breed. So a Wolbachia-based approach would never drive a mosquito to extinction - it would just kill older individuals before they become capable of spreading dengue fever.

It also means that the mosquito is under very little pressure to evolve resistance to the bacterium, because it's quite capable to raising hundreds of offspring before its life is cut short. Indeed, there's no evidence that Drosophila (the natural host of wMelPop) has evolved any resistance to it in over a decade.

You could, however, imagine that the loss of older mosquitoes would simply trigger the evolution of dengue viruses that develop more rapidly. It's certainly a potential downer, but the viruses are already under such pressures because mosquito lives are so naturally short. The fact that they don't already develop quickly suggests that there's some cost in doing so even if quick-off-the-mark viruses do evolve, it's likely that they'll be weaker versions of existing ones.   

McMeniman's study is a promising start, but his enthusiasm is quite rightly tempered by a call for more research. His study hasn't shown that the approach would work, just that it can (and has a good chance of doing so). The next step is to do field-cage trials, where contained populations of infected mosquitoes are monitored under (mostly) natural conditions. And we'll need better models that simulate the spread of the bacterium and assess the potential for evolving resistance, no matter how small.

As a side note, this amusingly captioned image was released along with the paper. The caption reads: "Success of the experiments was dependent on human bloodfeeding of mosquitoes. That's McMeniman in the photo - he's a PhD student (read: the most junior person in the lab and, thus, lunch).


Reference: C. J. McMeniman, R. V. Lane, B. N. Cass, A. W.C. Fong, M. Sidhu, Y.-F. Wang, S. L. O'Neill (2009). Stable Introduction of a Life-Shortening Wolbachia Infection into the Mosquito Aedes aegypti Science, 323 (5910), 141-144 DOI: 10.1126/science.1165326

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What happens when the mosquitoes develop an immunity? Can scientists mutate the weaponized bacteria fast enough to keep up with compensatory mutations in mosquitoes undermining the weapon?

Great article on mosquito control. There is so much information out there and easy to miss the basic ones that may be more immediate and practical.

Biocontrol has received so little interest in the last three decades as the scientific direction focused on vaccines. We have also been working on understanding mosquito biocontrol through a different direction, i.e., using fishes that mimic the life cycle of mosquitoes in alternating wet and dry season. Although larvivorous fishes have had important contributions in malaria control in the last 100 years, the use of fish have declined with DDT and the increased focus on vaccine development which have yet to show real practical use. Annual fish represent the next step up in the use of larvivorous fish to feed on the aquatic stages of mosquitoes. The annual fish population can survive drought in temporary pools by depositing embryos in the substrate that can withstand dry conditions, perhaps using the same mechanism as the tardigrades you have written about recently. Just like the use of bacteria, mosquitoes are less likely to develop resistance against larval predators. Theoretically, once introduced in a temporary pool, the annual fish population can continue to maintain a population in such a habitat where no other fish can survive. Just recently, we have entered into a working agreement with the Tanzanian government to do a pilot field trial on using these indigenous fishes for biocontrol in temporary pools of freshwater.

If any of your readers might be interested in this, I have some background information on annual fish biology in the following links.…

Looking forward to your comments.

Jonathan R. Matias

The comments on use of annual killifish by Jonathan Matias are interesting. I think annuals would be useful in many situations. DNA analyis by Murphy and Collier (1997) supports the idea of New World and African Aplocheiloids as sister groups. Annuals appear scattered around among non-annuals; so I think looking at annualism from a phylogenetic viewpoint rather than as a unified phenomenon would be fruitful. Take a look at Jason Podrabsky's publications on Austrofuldulus. My 1971 paper on Rachovia hummelincki was based on misidentification of its sister species, which we later described as Rachovia pyropunctata. Oh well! There is a Podrabsky and Hrbek paper on pool limnology which documents the different water chemistry of pools inhabited by the two species.

'Fertilized embryos' is not correct, it is rather, 'fertilized eggs'.

By Jim Thomerson (not verified) on 03 Jan 2009 #permalink

perhaps I'll seem silly for pointing it out, but the LOLbachia is freakin' hilarious. ^_^

By Christine (not verified) on 07 Jan 2009 #permalink

I also think it is teh awesome

Man, you guys are smart. How I know this is that I actually understood what you said, but only because you spoke in conversational English! And I laughed like silly when I read the translation of "PhD student": mosquito bait, a la jr. scientist! Have fun, and let me know when "evolve" changes flavor from "Who is God?" to "Hello, God!" It's more fun knowing Him than being a distant observer in a lab!
I am researching, quote-unquote, leishmaniasis out of concern for the kids in Iraq, one of whom is my son. He is serving (time) in a locked down Army base, only helping when called upon by the Iraqi government. Strange place to be. Sitting duck no bull!

By Sue Ferenczy (not verified) on 20 Jul 2009 #permalink