The microbiome composition of Aedes aegypti is not critical for Wolbachia-mediated inhibition of dengue virus

Abstract

BackgroundDengue virus (DENV) is primarily vectored by the mosquito Aedes aegypti, and is estimated to cause 390 million human infections annually. A novel method for DENV control involves stable transinfection of Ae. aegypti with the common insect endosymbiont Wolbachia, which mediates an antiviral effect. However, the mechanism by which Wolbachia reduces the susceptibility of Ae. aegypti to DENV is not fully understood. In this study we assessed the potential of resident microbiota, which can play important roles in insect physiology and immune responses, to affect Wolbachia-mediated DENV blocking.Methodology/FindingsThe microbiome of Ae. aegypti stably infected with Wolbachia strain wMel was compared to that of Ae. aegypti without Wolbachia, using 16s rDNA profiling. Our results indicate that although Wolbachia affected the relative abundance of several genera, the microbiome of both the Wolbachia-infected and uninfected mosquitoes was dominated by Elizabethkingia and unclassified Enterobacteriaceae. To assess the potential of the resident microbiota to affect the Wolbachia-mediated antiviral effect, we used antibiotic treatment before infection with DENV by blood-meal. In spite of a significant shift in the microbiome composition in response to the antibiotics, we detected no effect of antibiotic treatment on DENV infection rates, or on the DENV load of infected mosquitoes.Conclusions/SignificanceOur findings indicate that stable infection with Wolbachia strain wMel produces few effects on the microbiome of laboratory-reared Ae. aegypti. Moreover, our findings suggest that the microbiome can be significantly altered without affecting the fundamental DENV blocking phenotype in these mosquitoes. Since Ae. aegypti are likely to encounter diverse microbiota in the field, this is a particularly important result in the context of using Wolbachia as a method for DENV control.

Metagenomic analysis of Aedes aegypti and Culex quinquefasciatus mosquitoes from Grenada, West Indies

“…No major human pathogens transmitted by C. quinquefasciatus have been reported in Grenada, but the mosquito is capable of transmitting several arboviruses that occur in other Caribbean islands (e.g., WNV, St. Louis Encephalitis virus) or in neighboring mainland South American countries (e.g., Wuchereria bancrofti) [17]. The microbial composition of A. aegypti and C. quinquefasciatus mosquitoes has been previously studied [18,19,[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. However, several arthropod-borne diseases that are endemic to the mainland Americas are not believed to be established in Caribbean islands (e.g.…”

Host, Symbionts, and the Microbiome: The Missing Tripartite Interaction

“…In contrast, a stable infection with Wolbachia in laboratory-reared mosquitoes (A. aegypti) had only few effects on the microbiome. Moreover, significant changes in the microbiome composition did not affect the dengue-virus-blocking phenotype caused by Wolbachia infection in this host [40]. However, analyses of A. aegypti transinfected with Wolbachia, released in the field in Brazil and Vietnam to inhibit the dengue virus, revealed that Wolbachia increases susceptibility of mosquitoes to dengue infection.…”

“…A good example of this is the Wolbachia-mediated inhibition of dengue virus. Under laboratory conditions it was indicated that the microbiome composition of the mosquito Aedes aegypti is not critical for inhibition [40]. However, when released into the wild, the picture became more complex.…”

Next Generation Biological Control: The Need for Integrating Genetics and Evolution

“…Such transfection applications require careful testing, as Wolbachia phenotypes are not always the same between species (Veneti et al, 2012). Also, Wolbachia can reduce the relative number of other potentially beneficial symbiotic bacteria (Audsley, Ye, & McGraw, 2017;Ye et al, 2017) and conversely, other microbiota can outcompete Wolbachia (Kondo, Shimada, & Fukatsu, 2005;Goto, Anbutsu, & Fukatsu, 2006;Hughes, Rivero, & Rasgon, 2014;Rossi et al, 2015). These competition dynamics within microbiomes (Brinker et al, 2019;Gurung et al, 2019) are an important consideration when releasing manipulated strains into the field, as is the fact that new microbes introduced via hosts may become permanent fixtures in their ecosystem.…”