Affordable Access

deepdyve-link
Publisher Website

Downregulation of a novel flagellar synthesis regulator AsiR promotes intracellular replication and systemic pathogenicity of Salmonella typhimurium.

Authors
  • Ma, Shuangshuang1, 2
  • Jiang, Lingyan1, 2
  • Wang, Jingting1, 2
  • Liu, Xiaoqian1, 2
  • Li, Wanwu1, 2
  • Ma, Shuai1, 2
  • Feng, Lu1, 2
  • 1 The Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Nankai University , Tianjin, China. , (China)
  • 2 TEDA Institute of Biological Sciences and Biotechnology, Tianjin Key Laboratory of Microbial Functional Genomics, Nankai University , Tianjin, China. , (China)
Type
Published Article
Journal
Virulence
Publisher
Landes Bioscience
Publication Date
Dec 01, 2021
Volume
12
Issue
1
Pages
298–311
Identifiers
DOI: 10.1080/21505594.2020.1870331
PMID: 33410728
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The intracellular pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) exploits host macrophage as a crucial survival and replicative niche. To minimize host immune response stimulated by flagellin, the expression of flagellar genes is downregulated during S. Typhimurium growth within host macrophages. However, the underlying mechanisms are largely unknown. In this study, we show that STM14_1285 (named AsiR), a putative RpiR-family transcriptional regulator, which is downregulated within macrophages as previously reported and also confirmed here, positively regulates the expression of flagellar genes by directly binding to the promoter of flhDC. By generating an asiR mutant strain and a strain that persistently expresses asiR gene within macrophages, we confirmed that the downregulation of asiR contributes positively to S. Typhimurium replication in macrophages and systemic infection in mice, which could be attributed to decreased flagellar gene expression and therefore reduced flagellin-stimulated secretion of pro-inflammatory cytokines IL-1β and TNF-α. Furthermore, the acidic pH in macrophages is identified as a signal for the downregulation of asiR and therefore flagellar genes. Collectively, our results reveal a novel acidic pH signal-mediated regulatory pathway that is utilized by S. Typhimurium to promote intracellular replication and systemic pathogenesis by repressing flagellar gene expression.

Report this publication

Statistics

Seen <100 times