AUTHOR=Kim Seul I , Kim Eunsuk , Yoon Hyunjin 

TITLE=σS-Mediated Stress Response Induced by Outer Membrane Perturbation Dampens Virulence in Salmonella enterica serovar Typhimurium

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.750940

DOI=10.3389/fmicb.2021.750940

ISSN=1664-302X

ABSTRACT=<p><italic>Salmonella</italic> alters cellular processes as a strategy to improve its intracellular fitness during host infection. Alternative <italic>σ</italic> factors are known to rewire cellular transcriptional regulation in response to environmental stressors. σ<sup>s</sup> factor encoded by the <italic>rpoS</italic> gene is a key regulator required for eliciting the general stress response in many proteobacteria. In this study, <italic>Salmonella</italic> Typhimurium deprived of an outer membrane protein YcfR was attenuated in intracellular survival and exhibited downregulation in <italic>Salmonella</italic> pathogenicity island-2 (SPI-2) genes. This decreased SPI-2 expression caused by the outer membrane perturbation was abolished in the absence of <italic>rpoS</italic>. Interestingly, regardless of the defects in the outer membrane integrity, RpoS overproduction decreased transcription from the common promoter of <italic>ssrA</italic> and <italic>ssrB</italic>, which encode a two-component regulatory system for SPI-2. RpoS was found to compete with RpoD for binding to the P<italic><sub>ssrA</sub></italic> region, and its binding activity with RNA polymerase (RNAP) to form Eσ<sup>s</sup> holoenzyme was stimulated by the small regulatory protein Crl. This study demonstrates that <italic>Salmonella</italic> undergoing RpoS-associated stress responses due to impaired envelope integrity may reciprocally downregulate the expression of SPI-2 genes to reduce its virulence.</p>