Nat Microbiol Wang Jingwen/Tang Huiru Collaborative Team Reveals the Mechanism of Symbiotic Bacteria Inhibiting Plasmodium Infection by Participating in Tryptophan Metabolism in Anopheles Mosquitoes

Editor-in-Chief | Anopheles mosquito guts are rich in symbiotic bacteria, which are crucial to the nutrient metabolism and disease-transmitting ability of Anopheles mosquitoes
.

After sucking blood, Anopheles mosquitoes digest hemoglobin to obtain a large amount of amino acids, among which the essential amino acid tryptophan is essential for Anopheles mosquitoes
.

It was previously unclear whether and how symbionts are involved in amino acid metabolism in Anopheles mosquitoes
.

On April 18, 2022, Professor Wang Jingwen and Professor Tang Huiru from the School of Life Sciences of Fudan University published an article in Nature Microbiology, Anopheline mosquitoes are protected against parasite infection by tryptophan catabolism in gut microbiota
.

This study found that symbiotic bacteria are involved in regulating the levels of various tryptophan metabolites in Anopheles mosquitoes, among which the accumulation of 3-hydroxykynurenine can destroy the intestinal periphagic membrane structure of Anopheles mosquitoes and promote Plasmodium infection
.

The kynureninase encoded by the symbiotic bacterium Pseudomonas alcaligenes can protect the peritrophic membrane by breaking down 3-hydroxykynurenine and improve the resistance of Anopheles mosquitoes to Plasmodium
.

In this study, we compared the levels of tryptophan metabolites in normal and commensal scavenging (antibiotic-treated) Anopheles mosquitoes by LC/MS, and found that a variety of tryptophan metabolites accumulated in commensal scavenging Anopheles
.

Experimental screening found that accumulation of the metabolite 3-hydroxykynurenine promotes Plasmodium infection
.

Further mechanistic studies found that the accumulation of 3-hydroxykynurenine would disrupt the peritrophic membrane structure of Anopheles mosquitoes, thereby promoting Plasmodium infection
.

By analyzing the structure and genome of Anopheles symbionts, the research team screened out Pseudomonas alcaligenes that can metabolize 3-hydroxykynurenine
.

Pseudomonas alcaligenes encodes kynureninase, which degrades 3-hydroxykynurenine
.

Mutation of this gene results in the loss of 3-hydroxykynurenine degradation by Pseudomonas alcaligenes, thereby increasing the susceptibility of Anopheles mosquitoes to Plasmodium
.

The above results indicate that Anopheles symbionts affect Plasmodium infection by regulating host tryptophan metabolism
.

For this work, Fudan University is the first unit.
The 2020 doctoral student Feng Yuebiao, the 2016 doctoral student Peng Yeqing, the 2021 doctoral student Song Xiumei and the 2020 undergraduate Wen Han are the co-first authors of the paper
.

Professor Wang Jingwen and Professor Tang Huiru from the School of Life Sciences of Fudan University are the co-corresponding authors
.

Original link: https:// Publisher: 11th reprint notice [Non-original article] The copyright of this article belongs to the author of the article, and you are welcome to forward and share it personally, without the author's Reprinting is prohibited, the author has all legal rights, and offenders will be held accountable
.