Microbial tryptophan catabolism affects the vector competence ofAnopheles

Abstract

The influence of microbiota on mosquito physiology and vector competence is becoming increasingly clear but our understanding of interactions between microbiota and mosquitoes still remains incomplete. Here we show that gut microbiota of Anopheles stephensi, a competent malaria vector, participates mosquito tryptophan metabolism. Elimination of microbiota by antibiotics treatment leads to the accumulation of tryptophan (Trp) and its metabolites, kynurenine (Kyn), 3-hydroxykynurenine (3-HK) and xanthurenic acid (XA). Of these, 3-HK impairs the structure of peritrophic matrix (PM), thereby promoting Plasmodium berghei infection. Among the major gut microbiota in An. stephensi, Pseudomonas alcaligenes plays a role in catabolizing 3-HK as revealed by whole genome sequencing and LC-MS metabolic analysis. The genome of P. alcaligenes encodes kynureninase (KynU) that is responsible for the conversion of 3-HK to 3-Hydroxyanthranilic acid (3-HAA). Mutation of this gene abrogates the ability of P. alcaligenes to metabolize 3-HK, which in turn abolishes its role on PM protection. Colonization of An. stephensi with KynU mutated P. alcaligenes fails to protect mosquitoes against parasite infection as effectively as those with wild type bacterium. In summary, we identify an unexpected function of gut microbiota in controlling mosquito tryptophan metabolism with the major consequences on vector competence.

The buzz in the field: the interaction between viruses, mosquitoes, and metabolism

“…A study by Feng et al, demonstrated the influence of gut microbiota of Anopheles stephensi (a potent malaria vector) on tryptophan metabolism. The study reported how elimination of gut microbiota via antibiotics increased accumulation of tryptophan and its metabolites (kynurenine and 3-hydroxykynurenine, 3H-K) in the mosquito with high levels of 3H-K leading to structural impairments in the peritrophic matrix which in turn facilitated Plasmodium berghei infection (Feng et al, 2021). Similar observations were also made by Das de et al (Das De et al, 2022),.…”

“…This is important to prevent Plasmodium spp. Infections (Okech et al, 2006;Lima et al, 2012;Feng et al, 2021;Bottino-Rojas et al, 2022). Microbiota also plays a role in enhancing/blocking viral infections by secreting metabolites or altering metabolic homeostasis (Apte-Deshpande et al, 2012;Ramirez et al, 2012;Apte-Deshpande et al, 2014;Ramirez et al, 2014).…”

Biochemical Evolution of a Potent Target of Mosquito Larvicide, 3-Hydroxykynurenine Transaminase

“…This metabolite induces Plasmodium berghei infection in Anopheles mosquitoes by damaging the structure of the peritrophic matrix in the midgut. Nevertheless, it has been shown that the gut microbiota (i.e., Pseudomonas alcaligenes ) in A. stephensi helps in improving the resistance towards malaria parasites by synthesizing the enzyme kynureninase that catabolizes 3-HK [ 5 , 6 ]. Although the potential toxicity of 3-HK has been highlighted in many studies, it remains present in various physiological functions as a compound of significance.…”

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

“…It has already been reported that tryptophan catabolism has a role in modulating insecticide tolerance in permethrin-treated Drosophila melanogaster [ 135 ]. Likewise, this pathway was described in Anopheles , where catabolism of 3-hydroxykynurenine (3-HK), a metabolite of tryptophan by Pseudomonas , had a role in vectorial competence, protecting mosquitoes against Plasmodium infection [ 136 ]. ATP-binding cassette (ABC) transporters regulated by a two-component system (TCSs) were another predicted function in Pseudomonas .…”