The ArcAB two-component regulatory system promotes resistance to reactive oxygen species and systemic infection by Salmonella Typhimurium

PLoS One. 2018 Sep 4;13(9):e0203497. doi: 10.1371/journal.pone.0203497. eCollection 2018.

Abstract

Salmonella enterica Serovar Typhimurium (S. Typhimurium) is an intracellular bacterium that overcomes host immune system barriers for successful infection. The bacterium colonizes the proximal small intestine, penetrates the epithelial layer, and is engulfed by macrophages and neutrophils. Intracellularly, S. Typhimurium encounters highly toxic reactive oxygen species including hydrogen peroxide and hypochlorous acid. The molecular mechanisms of Salmonella resistance to intracellular oxidative stress is not completely understood. The ArcAB two-component system is a global regulatory system that responds to oxygen. In this work, we show that the ArcA response regulator participates in Salmonella adaptation to changing oxygen levels and is also involved in promoting intracellular survival in macrophages and neutrophils, enabling S. Typhimurium to successfully establish a systemic infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Female
  • Humans
  • Mice
  • Microbial Viability*
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism*
  • Salmonella Infections / genetics
  • Salmonella Infections / metabolism*
  • Salmonella Infections / pathology
  • Salmonella typhimurium / genetics
  • Salmonella typhimurium / metabolism*
  • Salmonella typhimurium / pathogenicity*

Substances

  • Bacterial Proteins
  • Reactive Oxygen Species

Grants and funding

This work was supported by "Fondo Nacional de Ciencia y Tecnologia" FONDECYT Grants #1120384 and #1160315 (to CPS), Grant PFB-16 (to RP) from "Comisión Nacional de Investigación Científica y Tecnológica de Chile" (CONICYT) and Universidad Andres Bello Nucleo Grant DI-3-17/N (to CPS), and Doctoral Fellowships were received from Comisión Nacional de Investigación Científica y Tecnológica de Chile" CONICYT (Grant 21150592 to CPE, Grant 21160858 to ACB, Grant 21151217 to JCS, and Grant 21180743 to CEC).