Association of Midgut Bacteria and Their Metabolic Pathways with Zika Infection and Insecticide Resistance in Colombian Aedes aegypti Populations

Abstract

Introduction: Aedes aegypti is the vector of several arboviruses such as dengue, Zika, and chikungunya. In 2015–16, Zika virus (ZIKV) had an outbreak in South America associated with prenatal microcephaly and Guillain-Barré syndrome. This mosquito's viral transmission is influenced by microbiota abundance and diversity and its interactions with the vector. The conditions of cocirculation of these three arboviruses, failure in vector control due to insecticide resistance, limitations in dengue management during the COVID-19 pandemic, and lack of effective treatment or vaccines make it necessary to identify changes in mosquito midgut bacterial composition and predict its functions through the infection. Its study is fundamental because it generates knowledge for surveillance of transmission and the risk of outbreaks of these diseases at the local level. Methods: Midgut bacterial compositions of females of Colombian Ae. aegypti populations were analyzed using DADA2 Pipeline, and their functions were predicted with PICRUSt2 analysis. These analyses were done under the condition of natural ZIKV infection and resistance to lambda–cyhalothrin, alone and in combination. One-step RT-PCR determined the percentage of ZIKV-infected females. We also measured the susceptibility to the pyrethroid lambda–cyhalothrin and evaluated the presence of the V1016I mutation in the sodium channel gene. Results: We found high ZIKV infection rates in Ae. aegypti females from Colombian rural municipalities with deficient water supply, such as Honda with 63.6%. In the face of natural infection with an arbovirus such as Zika, the diversity between an infective and non-infective form was significantly different. Bacteria associated with a state of infection with ZIKV and lambda–cyhalothrin resistance were detected, such as the genus Bacteroides, which was related to functions of pathogenicity, antimicrobial resistance, and bioremediation of insecticides. We hypothesize that it is a vehicle for virus entry, as it is in human intestinal infections. On the other hand, Bello, the only mosquito population classified as susceptible to lambda–cyhalothrin, was associated with bacteria related to mucin degradation functions in the intestine, belonging to the Lachnospiraceae family, with the genus Dorea being increased in ZIKV-infected females. The Serratia genus presented significantly decreased functions related to phenazine production, potentially associated with infection control, and control mechanism functions for host defense and quorum sensing. Additionally, Pseudomonas was the genus principally associated with functions of the degradation of insecticides related to tryptophan metabolism, ABC transporters with a two-component system, efflux pumps, and alginate synthesis. Conclusions: Microbiota composition may be modulated by ZIKV infection and insecticide resistance in Ae. aegypti Colombian populations. The condition of resistance to lambda–cyhalothrin could be inducing a phenome of dysbiosis in field Ae. aegypti affecting the transmission of arboviruses.

Comparative analysis of midgut bacterial communities in Chikungunya virus-infected and non-infected Aedes aegypti Thai laboratory strain mosquitoes

“…However, the bacterial community undergoes dynamic changes throughout the life cycle of mosquitoes, with composition variations based on factors such as mosquito gender, developmental stage, and ecological conditions 42 . Therefore, these variations in microbiota composition may help elucidate the vector competence commonly observed across mosquito populations 43 . Additionally, microbiota can influence mosquito development 19 , nutrient acquisition 44 , blood digestion 45 , and the synthesis of the peritrophic matrix 46 .…”

Microbial exposure across life reduces susceptibility ofAedes aegyptito Zika virus by enhancing blood digestion and limiting midgut cell infection

“…aegypti , blood-derived heme induces iron- and ROS-dependent signaling that also regulates immune genes, affecting DENV susceptibility (85). Metabolism of Bacteroides associates with elevated ZIKV susceptibility and conditions insecticide resistance (86), implicating a complex metabolic network that can also influence arbovirus susceptibility. Further investigation of the relationship between blood digestion and immunity could uncover novel determinants of mosquito vector competence.…”

A tangled threesome: understanding arbovirus infection in Aedes spp. and the effect of the mosquito microbiota

“…increase AMPs production by activating the Toll pathway, thus reducing DENV infection ( Figure 2A -VI), and Beauveria bassiana fungus in A. aegypti activates the JAK-STAT and Toll pathways, thereby increasing resistance to DENV (Dong et al, 2012 ). In contrast, DENV can induce AMPs production to reduce gut microbiota (Ramirez et al, 2012 ), ZIKV has also been reported to modulate microbiota composition (Arévalo-Cortés et al, 2022 ). Microbiota bacteria also affect the development of Serratia (Kozlova et al, 2021 ).…”