When a male mosquito with Wolbachia mates with a female that lacks the bacteria, the eggs she lays do not hatch

In the mid-1990s, Seymour Benzer, a physicist-turned-biologist whose seminal work helped establish the field of behavioural genetics, and a post-doctoral researcher in his lab, Kyung-Tai Min, were screening the fruit fly, Drosophila melanogaster, looking for gene mutations that caused brain degeneration. Serendipitously, they found a strain of Wolbachia bacteria that proliferated when the fly reached adulthood and brought about its early death.

In a paper published in the Proceedings of the National Academy of Sciences (PNAS) in 1997, they called this bacterial strain popcorn. “The Wolbachia pop up and proliferate in the brain [of the fly] like popcorn,” Dr. Min, now a professor at the Ulsan National Institute of Science and Technology in South Korea, said in an email, explaining why such a sobriquet was given.

At the time, Australian scientist Scott O’Neill was at Yale University in the U.S., trying to use Wolbachia to carry genes into insect populations that could reduce the latter’s capacity to transmit diseases such as dengue and malaria.

“We were having trouble getting that technology to work,” he told this correspondent. The PNAS paper offered a simpler alternative. “Knowing that lifespan is such a critical determinant for disease transmission, we got very interested.” Work on introducing the life-shortening Wolbachia strain into mosquitoes began immediately.

That line of research proved fruitful. It led to the ‘Eliminate Dengue Program’ (www.eliminatedengue.com), an international not-for-profit collaboration, headed by Dr. O.Neill, that seeks to use Wolbachia bacteria for dengue control.

Wolbachia-carrying Aedes aegypti mosquitoes, the primary transmitter of dengue in much of the world, are being field tested in northern Australia. Trials have also begun in Vietnam and Indonesia, and similar trials are planned in Brazil and Colombia too.

However, adapting the popcorn strain of Wolbachia so that it would thrive in A. aegypti mosquitoes was not easy and took many years to achieve. Finally, in a paper published in Science in early 2009, Dr. O’Neill and his colleagues were able to announce that they had succeeded.

By then, his lab had moved from Yale University to the University of Queensland in Australia.

When a male mosquito with Wolbachia mates with a female that lacks the bacteria, the eggs she lays do not hatch. A Wolbachia-infected female can, on the other hand, mate with either infected or uninfected males and successfully produce progeny, which inherit the bacteria from her. As a result, when male and female mosquitoes carrying Wolbachia are released to breed with wild mosquitoes in an area, the bacteria ought to rapidly spread in the mosquito population there.

It also turned out that the bacteria greatly reduced the replication of the dengue virus and its spread inside the body of the mosquito, which should curb the risk of such mosquitoes passing the virus to humans they feed on. (Studies have indicated that Wolbachia could similarly cut transmission of other viruses carried by the same mosquito, such as those causing chikungunya, yellow fever and West Nile disease.)

“It became very apparent then that this effect was much stronger than the life-shortening effect would be. So we shifted the strategy of the programme away from life-shortening to just looking at direct interference between Wolbachia and dengue virus,” remarked Dr. O'Neill, who is currently at Australia's Monash University.

Besides, the mosquito-adapted form of the popcorn strain was found to greatly affect the fitness of its insect host, drastically reducing the latter's lifespan as well as the number of eggs females laid.

But another, more benign Wolbachia strain from the fruit fly that was adapted to grow in A. aegypti has shown encouraging results.

Two back-to-back papers published in the same issue of Nature in 2011 noted that this wMel strain placed less fitness costs on the mosquito while limiting its ability to transmit the dengue virus.

In early 2011, some 1.5 lakh adult male and female mosquitoes with wMel were released in each of two suburbs of the northern Australian city of Cairns. Within a short period, the bacterial strain had spread to almost all mosquitoes in those suburbs.

A year later, field-collected mosquitoes from the two suburbs were found to have retained the wMel bacteria and, consequently, continued to show reduced dengue infection and replication, according to a paper recently published in PLOS Neglected Tropical Diseases. Although mosquitoes come in from other areas, weekly monitoring showed that Wolbachia rates among mosquitoes has tended to be over 95 per cent in both suburbs, said Dr. O’Neill.

Mosquitoes bearing the bacteria were later released in other parts of Cairns.

Although there had been 75 cases of dengue in the city since last December, no local dengue transmission occurred in areas where Wolbachia mosquitoes were released, according to an update posted on the Eliminate Dengue Program’s website last month.

Dengue is not endemic in Australia and such outbreaks occur when travellers bring the virus into an area with A. aegypti mosquitoes.

It will be trials in dengue-endemic countries — which have started in Vietnam and Indonesia and are to be taken up in Brazil and Colombia — that show whether releasing mosquitoes with Wolbachia can lead to reduced disease burden in communities.

“We need quite large trials to be able to do that,” observed Dr. O’Neill.

Meanwhile, a pipeline of new Wolbachia strains, with stronger dengue blocking and better fitness characteristics, was being developed that should go into trials over the next two years, he said.

In addition, a trial is being carried out in China to see whether dengue transmission by another mosquito, Aedes albopictus, could be similarly curtailed by introducing a entirely new Wolbachia strain into it. (This mosquito is already naturally infected with two Wolbachia strains.)

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