Role of RpoS in Regulating Stationary Phase Salmonella Typhimurium Pathogenesis-Related Stress Responses under Physiological Low Fluid Shear Force Conditions.

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 the log phase. These log phase LFS-induced phenotypes were independent of the master stress response regulator, RpoS (σS). 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 challenges of 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. IMPORTANCE Bacterial pathogens respond dynamically to a variety of stresses in the infected host, including physical forces of fluid flow (fluid shear) across their surfaces. While pathogens experience wide fluctuations in fluid shear during infection, little is known about how these forces regulate microbial pathogenesis. This is especially important for stationary-phase bacterial growth, which is a critical period to understand microbial resistance, survival, and infection potential, and is regulated in many bacteria by the general stationary-phase stress response protein RpoS. Here, we showed that, unlike conventional culture conditions, several stationary-phase Salmonella pathogenic stress responses were not impacted by RpoS when bacteria were cultured under fluid shear conditions relevant to those encountered in the intestine of the infected host. These findings offer new insight into how physiological fluid shear forces encountered by Salmonella during infection might impact pathogenic responses in unexpected ways that are relevant to their disease-causing ability.

Affective Temperament Traits and Age-Predicted Recreational Cannabis Use in Medical Students: A Cross-Sectional Study.

The use of cannabis among college students is increasing. Cannabis abuse has been proposed to be associated with personality dimensions. However, there are currently no known studies on the relationship of temperament traits and recreational cannabis use among college students. This is a cross-sectional study that investigated 328 students at a Podiatric Medical College. We evaluated the association between temperament and recreational cannabis use by the students. Temperament was investigated using the Memphis, Pisa, Paris and San Diego Auto- Questionnaire (TEMPS-A (short version)). Additionally, we assessed demographics variables and perceived stress in the context of cannabis use, and analyzed the findings using logistic regression. The prevalence of recreational cannabis use was 8.45%. Recreational cannabis use among these students was highly associated with irritable and cyclothymic temperament traits. There was no association between recreational cannabis use and perceived stress, and demographic variables or other substance use. Furthermore, logistic regression analysis indicated that higher scores in cyclothymic or irritable temperament traits are significant predictors for recreational cannabis use. Our study has identified key temperament traits, with a strong association with recreational use of cannabis of the studied student population. Our findings are useful in designing screening and educational strategies directed towards increasing the wellbeing of medical students.