Anti-Microbiota Vaccines Modulate the Tick Microbiome in a Taxon-Specific Manner

Abstract

The lack of tools for the precise manipulation of the tick microbiome is currently a major limitation to achieve mechanistic insights into the tick microbiome. Anti-tick microbiota vaccines targeting keystone bacteria of the tick microbiota alter tick feeding, but their impact on the taxonomic and functional profiles of the tick microbiome has not been tested. In this study, we immunized a vertebrate host model (Mus musculus) with live bacteria vaccines targeting keystone (i.e., Escherichia-Shigella) or non-keystone (i.e., Leuconostoc) taxa of tick microbiota and tested the impact of bacterial-specific antibodies (Abs) on the structure and function of tick microbiota. We also investigated the effect of these anti-microbiota vaccines on mice gut microbiota composition. Our results showed that the tick microbiota of ticks fed on Escherichia coli-immunized mice had reduced Escherichia-Shigella abundance and lower species diversity compared to ticks fed on control mice immunized with a mock vaccine. Immunization against keystone bacteria restructured the hierarchy of nodes in co-occurrence networks and reduced the resistance of the bacterial network to taxa removal. High levels of E. coli-specific IgM and IgG were negatively correlated with the abundance of Escherichia-Shigella in tick microbiota. These effects were not observed when Leuconostoc was targeted with vaccination against Leuconostoc mesenteroides. Prediction of functional pathways in the tick microbiome using PICRUSt2 revealed that E. coli vaccination reduced the abundance of lysine degradation pathway in tick microbiome, a result validated by qPCR. In contrast, the gut microbiome of immunized mice showed no significant alterations in the diversity, composition and abundance of bacterial taxa. Our results demonstrated that anti-tick microbiota vaccines are a safe, specific and an easy-to-use tool for manipulation of vector microbiome. These results guide interventions for the control of tick infestations and pathogen infection/transmission.

Vector microbiota manipulation by host antibodies: the forgotten strategy to develop transmission-blocking vaccines

“…Functional host antibodies have been shown to interact with symbionts in R. prolixus [ 82 ] and Glossina morsitans [ 83 ] as well as with bacterial microbiota in mosquitoes [ 84 ] and ticks [ 25 , 26 ]. Rhodnius prolixus fed exclusively on blood from rabbits immunized against Rhodoccocus rhodnii have developmental alterations such as prolonged molting times, incomplete development and malformed limbs [ 82 ].…”

“…More recently, anti-microbiota vaccines were designed to target specific taxa within tick microbiota [ 25 , 26 ]. The genus Escherichia - Shigella , identified as central in the tick microbial communities, was targeted with host antibodies [ 25 ].…”

“…The genus Escherichia - Shigella , identified as central in the tick microbial communities, was targeted with host antibodies [ 25 ]. Immunization of mice against live E. coli induced high levels of E. coli -specific IgM and IgG that were negatively correlated with the abundance of Escherichia - Shigella in tick microbiota [ 26 ]. The weight of nymph ticks that fed on E. coli -immunized mice increased significantly compared with ticks fed on mock-immunized mice.…”

“…Despite recent advances in vector microbiota research, the lack of tools for the precise and selective manipulation of the vector microbiome is currently a major limitation to achieving mechanistic insights into pathogen-microbiome interactions [ 20 , 24 ]. Recently, our team introduced anti-microbiota vaccines [ 25 ] as an innovative approach to vector microbiome manipulation [ 26 ] and the development of novel pathogen transmission-blocking vaccines [ 27 ]. Host immunization with keystone taxa (i.e.…”

“…Tick mortality was associated with a host antibody response against the carbohydrate Galα1-3Gal (α-Gal), a product of galactosyltransferase enzymes with genes widely present in the tick microbiota [ 25 ]. Anti-microbiota vaccines [ 25 , 26 ] can be used as a tool to induce bacterial-specific antibodies for microbiota manipulation and pathogen control. In this context, understanding the dynamics and activity of host antibodies within the vector becomes an important research area.…”