Bacteria-mediated hypoxia functions as a signal for mosquito development

Significance

Mosquitoes are important insects because several species transmit pathogens as adults that cause disease in humans and other vertebrates. One approach for control is preventing immature mosquitoes from developing into adults. Immature-stage mosquitoes require gut bacteria to develop, but the mechanisms underlying this dependence are unknown. Here, we identify cytochrome bd oxidase as a bacterial product involved in mosquito development. We also show that bacteria-mediated reduction of oxygen levels in the digestive tract of larvae serves as a signal for molting. These findings provide the first evidence that aerobic respiration by bacteria plays an essential role in mosquito development. This information can also potentially be used to develop tools for disabling the growth of larval mosquitoes into adults.

Abstract

Mosquitoes host communities of microbes in their digestive tract that consist primarily of bacteria. We previously reported that several mosquito species, including Aedes aegypti, do not develop beyond the first instar when fed a nutritionally complete diet in the absence of a gut microbiota. In contrast, several species of bacteria, including Escherichia coli, rescue development of axenic larvae into adults. The molecular mechanisms underlying bacteria-dependent growth are unknown. Here, we designed a genetic screen around E. coli that identified high-affinity cytochrome bd oxidase as an essential bacterial gene product for mosquito growth. Bioassays showed that bacteria in nonsterile larvae and gnotobiotic larvae inoculated with wild-type E. coli reduced midgut oxygen levels below 5%, whereas larvae inoculated with E. coli mutants defective for cytochrome bd oxidase did not. Experiments further supported that hypoxia leads to growth and ecdysone-induced molting. Altogether, our results identify aerobic respiration by bacteria as a previously unknown but essential process for mosquito development.