Abstract

The mosquito midgut microbiota has been shown to influence vector competence for multiple human pathogens. The microbiota is highly variable in the field, and the sources of this variability are not well understood, which limits our ability to understand or predict its effects on pathogen transmission. In this work, we report significant variation in female adult midgut bacterial load between strains of A. aegypti which vary in their susceptibility to dengue virus. Composition of the midgut microbiome was similar overall between the strains, with 81–92% of reads coming from the same five bacterial families, though we did detect differences in the presence of some bacterial families including Flavobacteriaceae and Entobacteriaceae. We conducted transcriptomic analysis on the two mosquito strains that showed the greatest difference in bacterial load, and found that they differ in transcript abundance of many genes implicated in amino acid metabolism, in particular the branched chain amino acid degradation pathway. We then silenced this pathway by targeting multiple genes using RNA interference, which resulted in strain-specific bacterial proliferation, thereby eliminating the difference in midgut bacterial load between the strains. This suggests that the branched chain amino acid (BCAA) degradation pathway controls midgut bacterial load, though the mechanism underlying this remains unclear. Overall, our results indicate that amino acid metabolism can act to influence the midgut microbiota. Moreover, they suggest that genetic or physiological variation in BCAA degradation pathway activity may in part explain midgut microbiota variation in the field.

Highlights

  • Aedes aegypti mosquitoes are a primary vector for multiple arboviruses that infect humans including dengue virus, chikungunya virus, yellow fever virus and Zika virus

  • To test for a role of mosquito genotype, we investigated whether adult females from multiple strains of A. aegypti vary in their midgut microbial load when reared under identical conditions

  • We investigated molecular processes that influence variation in female adult midgut bacterial load among A. aegypti strains

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Summary

Introduction

Aedes aegypti mosquitoes are a primary vector for multiple arboviruses that infect humans including dengue virus, chikungunya virus, yellow fever virus and Zika virus. Dengue alone inflicts a staggering disease burden, with approximately 3.9 billion people globally at risk of contracting the virus [1] and an estimated prevalence of 390 million cases per year [2] Because of their central role in pathogen transmission, understanding vector competence of Aedes mosquitoes is critically relevant to developing new methods of reducing this disease burden and improving public health. One issue complicating our ability to understand and/or predict vector competence is the fact that it varies substantially in natural populations [3] This variation has been attributed in part to both genetic heterogeneity as well as environmental factors such as temperature [4,5,6,7]. One additional factor that has the potential to influence variation in vector competence is the mosquito midgut microbiota [8]

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