Bacteria found to block the transmission of mosquito-borne infections show long-term viability as a biocontrol agent, alleviating concern that this benefit could diminish over time, according to a study published in the journal Nature Microbiology.
The researchers also identified a gene that could explain how the bacteria disrupts the spread of disease.
Wolbachia bacteria live inside many insect cells, but not in A. aegypti. Because of their ability to block viruses and reduce infection, they have been introduced into mosquitoes in several countries, including Australia, Brazil, Colombia, Vietnam and Indonesia, since 2011.
Although Wolbachia were found to reduce viral infections, an international research team led by Elizabeth McGraw from Pennsylvania University, US, writes that “the evolutionary stability of viral blocking is unknown”.
“There has been concern that dengue virus could evolve an ability to sneak past Wolbachia or that the insects themselves could evolve resistance to Wolbachia,” explains McGraw.
To investigate the bacteria’s long-term impact, the team selected A. aegypti mosquitoes with genes that conferred high or low virus blocking ability and compared them to each other and a randomly selected control group, repeating each selection on three different populations.
For all nine resulting groups, four rounds of selection were carried out, and 200 offspring were taken from six selected mosquitoes for each population and generation.
Using genetic sequencing studies, the team measured the impacts of the genes on mosquito fitness – the ability to survive and reproduce.
They found that mosquitoes with weaker viral blocking ability also had lower fitness, indicating that evolutionary processes could continue their success at blocking the viruses.
“We found that mosquitoes exhibiting better blocking had increased fitness, at least under idealised conditions in the laboratory,” says McGraw, “suggesting the potential for natural selection to maintain blocking”.
Comparing the populations also revealed a gene – AAEL023845, a cadherin protein involved in cell-cell adhesion – related to the mosquitoes’ blocking strength.
“Increased expression of this gene was associated with increased Wolbachia-mediated protection against viruses,” says first author Suzanne Ford.
The findings shed light on the mechanism behind the bacteria’s mode of action, a question that researchers have long grappled with.
A prior theory proposed that the bacteria, being a foreign substance, might trigger the mosquitoes’ immune systems and in turn suppress virus activity. Alternatively, it was thought that Wolbachia could be competing with viruses for nutrients or space within the insects.
“Our data do not support either of these theories,” says McGraw. “Instead, our results suggest that the cadherin gene may affect cell-cell signalling or movement of viruses within cells, altering the virus’s ability to enter cells, replicate within them and then exit.”
The team suggests the findings offer new directions for studying Wolbachia’s dengue virus blocking activity and exploring its impact on other viruses spread by A. aegypti.