100 Years of Wolbachia

By Olivia Conway

In the past several decades, researchers and physicians have made tremendous advances towards reducing the death rates of genetic disorders and cancers, but effective treatments and preventative measures for mosquito-borne illnesses have remained elusive. Amounting to 17% of all cases of infectious disease, illnesses like Zika, dengue, malaria, and chikungunya wreak havoc on tropical regions of the globe every year, and the warming climate will only expand their range. Currently, public health organizations use bed nets and chemical insecticides to protect vulnerable communities from mosquito bites, but regular insecticide treatment can be expensive, and mosquito populations have demonstrated resistance to commonly-used chemical agents. 

Combined with a lack of strong healthcare infrastructure in affected areas and the absence of reliable treatments, the waning efficacy of known preventative interventions has inspired researchers to look elsewhere for a response to mosquito-borne infection. Their solution emerged from an unconventional, but ancient, idea: Using a bacteria called Wolbachia, which naturally infects insects like mosquitoes, to slow the spread of dangerous disease.

Wolbachia was discovered in 1924, but research on the bacterium did not begin in earnest until the 1980s, leading to a landmark 2009 discovery that mosquitoes infected with Wolbachia transmit dengue virus less effectively than uninfected ones. Due to an evolutionary anomaly, the most dangerous species of mosquito–Aedes aegypti, which carries dengue, and members of the genus Anopheles, which carry malaria–do not naturally exhibit the strains of Wolbachia that reduce viral transmission, but scientists have been able to carefully inject the bacterium into their eggs. The specific mechanism by which Wolbachia prevents dengue infection remains unclear, but these molecular mysteries have not deterred public health researchers from launching regional trials with their artificially-infected mosquitoes. 

Of course, this method of disease control can only have a meaningful effect if an overwhelming majority of global mosquito populations becomes infected with Wolbachia. The prospect of painstakingly infecting each individual mosquito with the bacterium is both daunting and impossible, but a natural quirk of Wolbachia biology has solved that problem for us. Wolbachia is maternally transmitted to new generations of mosquitoes, and a phenomenon called cytoplasmic incompatibility ensures that an infected male mosquito and an uninfected female mosquito cannot reproduce. Therefore, Wolbachia manipulates mosquito reproduction to favor offspring of infected female mosquitoes. Researchers theorize that releasing female mosquitoes infected with Wolbachia into the wild will allow the bacteria to spread naturally, gradually rendering the majority of the mosquito population unable to transmit deadly viruses.

Cytoplasmic incompatibility can help spread Wolbachia among mosquito populations. Image source.

Current evidence indicates that Wolbachia is harmless to humans, and the infected mosquitoes seem to pose a negligible threat to the environment. Since 2011, the World Mosquito Program has released A. aegypti mosquitoes infected with Wolbachia in several countries with high rates of mosquito-borne illness and tracked the incidence of human disease. It can be difficult to measure the efficacy of this intervention, but early results seem promising: In 2021, several years after the mosquitoes were released in Medellín, Colombia, data reported the lowest rates of dengue infection in two decades. 

While these initial successes are exciting, implementing this program at a larger scale presents significant challenges. Infecting mosquitoes with Wolbachia and releasing them into the wild requires lab equipment, trained workers, and volunteers, and the mosquitoes’ genetic information needs to be periodically assessed after the release. Additionally, researchers acknowledge that each mosquito species may require a different strain of Wolbachia to optimize viral prevention. Even with these caveats, the potential of a novel approach to mitigating deadly disease is something to celebrate.  

Edited by Daniela Danilova