Glucose-mediated proliferation of a gut commensal bacterium promotes Plasmodium infection by increasing mosquito midgut pH

Abstract

SUMMARY Plant-nectar-derived sugar is the major energy source for mosquitoes, but its influence on vector competence for malaria parasites remains unclear. Here, we show that Plasmodium berghei infection of Anopheles stephensi results in global metabolome changes, with the most significant impact on glucose metabolism. Feeding on glucose or trehalose (the main hemolymph sugars) renders the mosquito more susceptible to Plasmodium infection by alkalizing the mosquito midgut. The glucose/trehalose diets promote proliferation of a commensal bacterium, Asaia bogorensis , that remodels glucose metabolism in a way that increases midgut pH, thereby promoting Plasmodium gametogenesis. We also demonstrate that the sugar composition from different natural plant nectars influences A. bogorensis growth, resulting in a greater permissiveness to Plasmodium . Altogether, our results demonstrate that dietary glucose is an important determinant of mosquito vector competency for Plasmodium , further highlighting a key role for mosquito-microbiota interactions in regulating the development of the malaria parasite.

Anti-Microbiota Vaccine Reduces Avian Malaria Infection Within Mosquito Vectors

“…in PS-exposed A. gambiae ( 42 ). Commensal Asaia bogorensis remodels glucose metabolism and increases midgut pH which in turn induces P. berghei gametogenesis and facilitates parasite infection of A. stephensi ( 10 ). Thus, the decrease of Enterobacteriaceae abundance may be balanced by the increase of another taxon (e.g., Asaia sp.)…”

“…In general, the susceptibility of mosquitoes to Plasmodium parasites infection is under genetic control (6)(7)(8), but the large variability in oocyst number among closely related mosquitoes indicates that environmental factors also play a role. Of special interest are the interactions between the vector, its microbiota and transmitted pathogens, since commensal bacteria interact with mosquito-borne pathogens (9) and can facilitate (10) or compete (11) with pathogen colonization and development within the vector midguts, prompting research into microbiota manipulation and transmission-blocking strategies (12). Depleting vector microbiota from bacteria that facilitates pathogen development could be exploited as a mean for blocking transmission.…”

“…Depleting vector microbiota from bacteria that facilitates pathogen development could be exploited as a mean for blocking transmission. For example, the bacterium Asaia bogorensis increases midgut pH promoting Plasmodium berghei gametogenesis within Anopheles stephensi ( 10 ), and high abundance of Enterobacteriaceae increases Plasmodium falciparum infection in Anopheles gambiae midgut ( 13 ), making the reduction of these bacterial species a sound strategy to reduce pathogen infection in the vector and potentially block transmission to the host.…”

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

“…Some species of Enterobacter, Escherichia, Serratia and Pseudomonas , commonly found in Anopheles mosquitoes, can markedly reduce intensities and prevalence of human and rodent malaria infection [ 36 ]. The bacterium Asaia bogorensis remodels glucose metabolism in a way that increases midgut pH, thereby promoting Plasmodium berghei (the agent of rodent malaria) gametogenesis within Anopheles stephensi [ 18 ], while Aedes mosquitoes positive for Serratia marcescens were more permissive to dengue virus infection [ 37 ]. The microbial communities of mosquito midgut have been shown to activate mosquito immune defense response to pathogen colonization [ 38 – 40 ].…”

“…The lack of these vitamins has been associated with developmental atrophies in the larval stages of mosquitoes [ 16 ]. Of special interest are the interactions between the vector, its microbiota and transmitted pathogens since commensal bacteria interact with vector-borne pathogens [ 8 , 17 ] and can facilitate [ 18 ] or compete [ 19 ] with pathogen colonization and development within the vector midguts, prompting research into microbiota manipulation for blocking pathogen transmission [ 20 ].…”