QseC Mediates Salmonella enterica Serovar Typhimurium Virulence In Vitro and In Vivo

• Type of Material: Article
• Authors: Cristiano G. Moreira, The University of Texas Southwestern Medical Center; David Weinshenker, Emory University; Vanessa Sperandio, The University of Texas Southwestern Medical Center
• Language: English
• Date: 2010-03-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2010, American Society for Microbiology. All Rights Reserved.© 2010, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1128/IAI.01038-09
• Title of Journal or Parent Work: Infection and Immunity
• ISSN: 0019-9567
• Volume: 78
• Issue: 3
• Start Page: 914
• End Page: 926
• Grant/Funding Information: This work was supported by NIH grant UO1-AI077853 and by the Burroughs Wellcome Fund.
• Keywords: Infectious Diseases; IMMUNOLOGY; Life Sciences & Biomedicine; Science & Technology; INFECTIOUS DISEASES; III SECRETION SYSTEM; Immunology; EPITHELIAL-CELLS; SENSOR KINASE; PATHOGENICITY ISLAND 2; GENE-EXPRESSION; BACTERIAL INTERNALIZATION; ENTEROHEMORRHAGIC ESCHERICHIA-COLI; NONPHAGOCYTIC CELLS; ANTIMICROBIAL PEPTIDE; HOST-CELLS
• Research Categories: Chemistry, Biochemistry; Biology, Microbiology

Abstract

The autoinducer-3 (AI-3)/epinephrine (Epi)/norepinephrine (NE) interkingdom signaling system mediates chemical communication between bacteria and their mammalian hosts. The three signals are sensed by the QseC histidine kinase (HK) sensor. Salmonella enterica serovar Typhimurium is a pathogen that uses HKs to sense its environment and regulate virulence. Salmonella serovar Typhimurium invades epithelial cells and survives within macrophages. Invasion of epithelial cells is mediated by the type III secretion system (T3SS) encoded in Salmonella pathogenicity island 1 (SPI-1), while macrophage survival and systemic disease are mediated by the T3SS encoded in SPI-2. Here we show that QseC plays an important role in Salmonella serovar Typhimurium pathogenicity. A qseC mutant was impaired in flagellar motility, in invasion of epithelial cells, and in survival within macrophages and was attenuated for systemic infection in 129x1/SvJ mice. QseC acts globally, regulating expression of genes within SPI-1 and SPI-2 in vitro and in vivo (during infection of mice). Additionally, dopamine β-hydroxylase knockout (Dbh -/- ) mice that do not produce Epi or NE showed different susceptibility to Salmonella serovar Typhimurium infection than wild-type mice. These data suggest that the AI-3/Epi/NE signaling system is a key factor during Salmonella serovar Typhimurium pathogenesis in vitro and in vivo. Elucidation of the role of this interkingdom signaling system in Salmonella serovar Typhimurium should contribute to a better understanding of the complex interplay between the pathogen and the host during infection.