Wolbachia: How the world’s most successful insect symbiont is being used to eliminate dengue

A reproductive parasite or humanity’s latest public health weapon?

Writer: Sophie Maho Chan
Editor: Altay Shaw
Artist: Stephanie Chang

Symbiosis is often presented in a black-and-white manner, categorised into either mutualism (beneficial), commensalism (neutral) or parasitism (harmful). When it comes to bacteria, we are particularly quick to discriminate between friends and foes. We notice no irony as we slather our hands with germ-killing antibiotics and slurp down ‘good bacteria’-restoring probiotics. However, in reality, biology is highly contextual. On a spectrum of host-symbiont interactions, a single bacterium can flexibly play the role of mutualist, parasite or even both — nowhere is this better demonstrated than in the bacteria genus Wolbachia.

It would be an understatement to call Wolbachia an evolutionary success. Experts predict they reside in over half of all insect species, making them the most prevalent endosymbiont on Earth. If this does not resonate with you, consider this: it is estimated there are at least two million species and 10 quintillion individual insects (that is 19 zeros) at any given moment. 

From nutrient supplementation to antiviral protection, Wolbachia are vital mutualists to some insects. However, a major part of their success lies in their capabilities as reproductive parasites. Dubbed the “master manipulators of invertebrate biology”, Wolbachia are notorious for hijacking the reproductive patterns of insect populations in wide-ranging ways. This includes feminising male embryos and selectively killing male progeny. As an extreme example, when an all-female asexual group of wasps was discovered, it turned out that Wolbachia were single-handedly responsible for converting unfertilised eggs that would otherwise harbour males into females; subjected to antibiotics, male populations were restored. The goal of all of this? Ensuring succession. Exclusively inherited down the maternal line, Wolbachia have “evolved many ways of screwing over male hosts to expand its pool of female ones”, as described by Ed Yong in his book I Contain Multitudes.

While Wolbachia have long been cast aside as “the bad guys” in evolution, this reputation is changing for the positive. By the late 20th century, scientists had already found that Wolbachia could prevent mosquito eggs from hatching as well as shorten insect lifespan, indicating their potential in disease control. The major breakthrough, however, was in 2008, when Wolbachia were proven to block a range of viruses from growing in Aedes aegypti mosquitoes altogether. Included were chikungunya virus, yellow fever virus, Zika virus and, of most relevance, dengue virus.

The idea of using bacteria to fight a mosquito-transmitted virus seems like a long-winded way to tackle the problem. Nevertheless, desperate times call for desperate measures. Dengue has been on the rise in recent decades, expanding its global reach and amplifying in areas where it was already endemic. In 2019, the World Health Organization recorded 4.2 million cases. Urbanisation, international travel and climate change are all furthering the rise of mosquito-transmitted diseases. With no available cure or treatment, killing A. aegypti mosquitoes has been the only solution — until now.

As A. aegypti mosquitoes do not naturally carry Wolbachia, scientists had to tinker with evolution and forge a new symbiosis in the lab. Working for over a decade, Scott O’Neill and his team discovered a way to artificially infect A. aegypti eggs with a fruit fly-derived strain of Wolbachia. Since infected female mosquitoes pass Wolbachia to their offspring with almost 100% reliability, the bacteria will efficiently spread through wild mosquito populations within a few generations, rendering them virus-free, at least in theory. 

2011 marked the first field trials of introducing Wolbachia-infected mosquitoes in northern Australia. The results were phenomenal. After releasing 10 mosquitoes per house per week for 10 weeks, more than 80% of the wild mosquitoes in the area carried Wolbachia. When further tested two months later, the local population still all carried Wolbachia and remained ‘immune’ to dengue. There have been no recorded outbreaks in the region for the last 5 years.

Today, the World Mosquito Program, formerly known as the Eliminate Dengue project and directed by O’Neill, has projects spanning 12 countries. As of December 2019, the programme has successfully colonised areas inhabited by five million people with Wolbachia-loaded mosquitoes. This year saw the first randomised controlled trial conducted in Yogyakarta, Indonesia, where dengue is endemic. Incidences of human infections were found to be 77% lower in regions where Wolbachia-infected mosquitoes were introduced compared to untreated regions. 

Risk assessments have confirmed the safety of Wolbachia. Furthermore, they are sustainable and cost-effective in comparison to insecticides which need to be sprayed continuously. Wolbachia also has various mechanisms through which it blocks viral replication, making it difficult for viruses to develop resistance. Nonetheless, experts warn that viral resistance is bound to develop and that we must also prepare for A. aegypti evolving resistance against Wolbachia.

The next step is to expand efforts to other mosquito-transmitted viruses. Ongoing projects in Brazil, previously affected by Zika and chikungunya epidemics, seem to confer positive results. However, since these diseases are periodic and unpredictable compared to dengue, producing reliable data from trials is a challenge. Others suggest that Wolbachia can even fight malaria, which is transmitted by a different species of mosquito. While only time will tell of its true efficacy, Wolbachia-infected mosquitoes offer us an exciting, novel approach to tackling diseases, by harnessing our biological understanding of symbiosis.

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