Role of RpoS in regulating stationary phase Salmonella Typhimurium pathogenesis-related stress responses under physiological low fluid shear force conditions

• Published in: mSphere Vol. 7; no. 4; p. e0021022
• Main Authors: Meléndez, Karla Franco, Crenshaw, Keith, Barrila, Jennifer, Yang, Jiseon, Gangaraju, Sandhya Rajiu, Davis, Richard R., Forsyth, Rebecca J., Ott, C. Mark, Kader, Rebin, III, Roy Curtiss, Roland, Kenneth, Nickerson, Cheryl A.
• Format: Journal Article
• Language: English
• Published: Johnson Space Center American Society for Microbiology 01-08-2022
• Subjects: biomechanical forces; fluid shear; Inorganic, Organic And Physical Chemistry; Life Sciences (General); Microbial Pathogenesis; Research Article; rotating wall vessel; RpoS; Salmonella; stationary-phase; mechanobiology; Salmonella; infection; σS (sigma S); RpoS; acid stress; rotating wall vessel; mechanotransduction; fluid shear; thermal stress; σ38 (sigma 38); stress responses; pathogenesis; stationary-phase; intestinal epithelium; sigma factor; bile salt stress; oxidative stress; biomechanical forces
• ISSN: 2379-5042; 2379-5042
• DOI: 10.1128/msphere.00210-22

The discovery that biomechanical forces regulate microbial virulence was established with the finding that physiological low fluid shear (LFS) forces altered gene expression, stress responses, and virulence of the enteric pathogen Salmonella enterica serovar Typhimurium during log phase. These log phase LFS-induced phenotypes were independent of the master stress response regulator, RpoS (S). Given the central importance of RpoS in regulating stationary phase stress responses of S. Typhimurium cultured under conventional shake flask and static conditions, we examined its role in stationary phase cultures grown under physiological LFS. We constructed an isogenic rpoS mutant derivative of wild type S. Typhimurium and compared the ability of these strains to survive in vitro pathogenesis-related stresses that mimic those encountered in the infected host and environment. We also compared the ability of these strains to colonize (adhere, invade, and survive within) human intestinal epithelial cell cultures. Unexpectedly, LFS-induced resistance of stationary phase S. Typhimurium cultures to acid and bile salts stresses did not rely on RpoS. Likewise, RpoS was dispensable for stationary phase LFS cultures to adhere to and survive within intestinal epithelial cells. In contrast, the resistance of these cultures to challenge with oxidative and thermal stresses, and their invasion into intestinal epithelial cells was influenced by RpoS. These findings expand our mechanistic understanding of how physiological fluid shear forces modulate stationary phase S. Typhimurium physiology in unexpected ways and provide clues into microbial mechanobiology and nuances of Salmonella responses to microenvironmental niches in the infected host.