Quorum sensing-activated phenylalanine metabolism drives OMV biogenesis to enhance mosquito commensal colonization resistance to Plasmodium

Yongmao Jiang; Han Gao; Lihua Wang; Wenqian Hu; Guandong Wang; Sibao Wang

doi:10.1016/j.chom.2023.08.017

Quorum sensing-activated phenylalanine metabolism drives OMV biogenesis to enhance mosquito commensal colonization resistance to Plasmodium

Cell Host Microbe. 2023 Oct 11;31(10):1655-1667.e6. doi: 10.1016/j.chom.2023.08.017. Epub 2023 Sep 21.

Authors

Yongmao Jiang¹, Han Gao¹, Lihua Wang¹, Wenqian Hu¹, Guandong Wang¹, Sibao Wang²

Affiliations

¹ CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, China.
² CAS Key Laboratory of Insect Developmental and Evolutionary Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai, China; CAS Center for Excellence in Biotic Interactions, University of Chinese Academy of Sciences, Beijing, China. Electronic address: sbwang@cemps.ac.cn.

PMID: 37738984
DOI: 10.1016/j.chom.2023.08.017

Abstract

Gut microbiota and its symbiotic relationship with the host are crucial for preventing pathogen infection. However, little is known about the mechanisms that drive commensal colonization. Serratia bacteria, commonly found in Anopheles mosquitoes, potentially mediate mosquito resistance to Plasmodium. Using S. ureilytica Su_YN1 as a model, we show that a quorum sensing (QS) circuit is crucial for stable colonization. After blood ingestion, the QS synthase SueI generates the signaling molecule N-hexanoyl-L-homoserine lactone (C6-HSL). Once C6-HSL binds to the QS receptor SueR, repression of the phenylalanine-to-acetyl-coenzyme A (CoA) conversion pathway is lifted. This pathway regulates outer membrane vesicle (OMV) biogenesis and promotes Serratia biofilm-like aggregate formation, facilitating gut adaptation and colonization. Notably, exposing Serratia Su_YN1-carrying Anopheles mosquitoes to C6-HSL increases Serratia gut colonization and enhances Plasmodium transmission-blocking efficacy. These findings provide insights into OMV biogenesis and commensal gut colonization and identify a powerful strategy for enhancing commensal resistance to pathogens.

Keywords: C6-HSL; N-hexanoyl-L-homoserine lactone; Plasmodium; QS; acetyl-CoA; biofilm-like aggregation; gut colonization; mosquito; outer membrane vesicles; phenylalanine.