SCIENCE@home

Succinate-driven virulence enhancement in hypervirulent Klebsiella pneumoniae via DcuSR two-component system

Guosheng Zhong,Xiaoya Yang,Ruting Deng,Jian-Ming Zeng,Jieying Pu,Cong Shen,Siyu Zhao,Tingting Yang,Huanliang Liu,M. Luo,Shibing Li,Cha Chen,Bin Huang

Published 2025 in Microbiology spectrum

ABSTRACT

ABSTRACT Hypervirulent Klebsiella pneumoniae (hvKP) primarily colonizes the mammalian gastrointestinal tract, and it is prone to causing invasive infections under specific conditions. To establish infection, hvKP must compete with the resident gut microbiota for essential nutrients. This study focuses on the C4-dicarboxylate (C4-DC) succinate, which has been reported to accumulate in the gut under specific pathological conditions. We demonstrate that hvKP utilizes succinate as a signaling molecule to enhance virulence gene expression. Specifically, extracellular succinate activates type VI secretion system gene expression via the DcuSR two-component system (TCS), thereby increasing cytotoxicity toward intestinal epithelial cells and enhancing competitiveness against commensal Escherichia coli. Additionally, succinate facilitates the expression of type III fimbriae via the DcuSR TCS, promoting hvKP adherence to intestinal epithelial cells. Beyond its signaling role, succinate functions as a metabolic substrate and contributes to adenosine 5′-triphosphate (ATP) synthesis, potentially through C4-dicarboxylic acid transporters DctA or DcuB to boost energy synthesis. This study focuses on elucidating the impact of succinate in regulating hvKP virulence, with particular attention to the potential role of the DcuSR TCS in hvKP pathogenesis. IMPORTANCE Succinate, a C4-DC, is produced by the host and the gut microbiota and can accumulate in the intestinal environment under various pathological conditions, such as diabetes and inflammatory bowel disease. It acts as a pivotal regulator of virulence traits and metabolic pathways in Enterobacteriaceae. Our findings highlight the significant impact of succinate on hvKP pathogenesis: (i) functioning through the DcuSR TCS to activate virulence programs and (ii) serving as a metabolic substrate that fuels bioenergetic adaptation through ATP synthesis. Succinate, a C4-DC, is produced by the host and the gut microbiota and can accumulate in the intestinal environment under various pathological conditions, such as diabetes and inflammatory bowel disease. It acts as a pivotal regulator of virulence traits and metabolic pathways in Enterobacteriaceae. Our findings highlight the significant impact of succinate on hvKP pathogenesis: (i) functioning through the DcuSR TCS to activate virulence programs and (ii) serving as a metabolic substrate that fuels bioenergetic adaptation through ATP synthesis.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-82 of 82 references · Page 1 of 1

CITED BY

  • No citing papers are available for this paper.

Showing 0-0 of 0 citing papers · Page 1 of 1