L-Arginine sensing regulates virulence gene expression and disease progression in enteric pathogens

Zelia Menezes-Garcia, Aman Kumar, Wenhan Zhu, Sebastian E. Winter, Vanessa Sperandio

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Microbiota, host and dietary metabolites/signals compose the rich gut chemical environment, which profoundly impacts virulence of enteric pathogens. Enterohemorrhagic Escherichia coli (EHEC) engages a syringe-like machinery named type-III secretion system (T3SS) to inject effectors within host cells that lead to intestinal colonization and disease. We previously conducted a high-throughput screen to identify metabolic pathways that affect T3SS expression. Here we show that in the presence of arginine, the arginine sensor ArgR, identified through this screen, directly activates expression of the genes encoding the T3SS. Exogenously added arginine induces EHEC virulence gene expression in vitro. Congruently, a mutant deficient in arginine transport (PartP) had decreased virulence gene expression. ArgR also augments murine disease caused by Citrobacter rodentium, which is a murine pathogen extensively employed as a surrogate animal model for EHEC. The source of arginine sensed by C. rodentium is not dietary. At the peak of C. rodentium infection, increased arginine concentration in the colon correlated with down-regulation of the host SLC7A2 transporter. This increase in the concentration of colonic arginine promotes virulence gene expression in C. rodentium. Arginine is an important modulator of the host immune response to pathogens. Here we add that arginine also directly impacts bacterial virulence. These findings suggest that a delicate balance between host and pathogen responses to arginine occur during disease progression.

Original languageEnglish (US)
Pages (from-to)12387-12393
Number of pages7
JournalProceedings of the National Academy of Sciences of the United States of America
Volume117
Issue number22
DOIs
StatePublished - Jun 2 2020

Keywords

  • ArgR
  • Arginine
  • EHEC

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'L-Arginine sensing regulates virulence gene expression and disease progression in enteric pathogens'. Together they form a unique fingerprint.

Cite this