Abstract 1254 Stress Response of Salmonella through sRNA-Mediated Regulation

The ability of certain species of bacteria to withstand or survive unfavorable environmental conditions such as desiccation (extreme dehydration) and carbon starvation displays a prominent example of the ability of cells to adapt to fluctuations in its surroundings. Since bacterial small noncoding RNA (sRNA) expressions are frequently associated with stress, we hypothesized that sRNAs likely contribute to Salmonella survival in low water environments. We have identified 173 sRNAs and >500 sRNAs in Salmonella that demonstrate responses to desiccation and carbon starvation, respectively. Gathered from our data, there are two principle strategies for bacterial survival during cellular stress: (1) active expression of molecular tools capable of dealing with specific stressors and (2) the generation of persister cells (comparatively metabolically dormant cells capable of prolonged survival in harsh environments). In either event, cumulative evidence suggests that sRNAs represent key regulators of Salmonella stress survival. We find that cells subjected to short term carbon starvation and cells subjected to long term carbon starvation have highly distinct sRNA profiles while sharing a few commonalities. We also observed highly distinct sRNA profiles associated with initial and prolong cellular desiccation. Furthermore, we also found significant overlaps between he sRNAs expressed in cells subjected to short durations of carbon starvation and desiccation, as well as significant overlaps between the sRNAs expressed during prolonged desiccation and long-term carbon starvation. We find that the sRNAs that are commonly induced during short term duration stress are expressed from promoters transcribed by the RNA polymerase (RNAP) Sigma subunit RpoS, and sRNAs commonly induced during long-term duration stress are expressed from promoters targeted by the RNAP Sigma subunit RpoE. Together, these findings have led us to hypothesize: Alternative RNAP Sigma subunit selection and consequent expression of distinct sets of sRNAs drive the decision between active stress resistance and persister formation in Salmonella. Therefore, as opposed to the currently accepted model of passive stoichiometric-based Sigma RNAP displacement, the central model tested by this work that alternative Sigma factors compete with one another through directing the transcription of distinct sets of sRNAs that inhibit opposing Sigma factors may constitute a general mechanism of prokaryotic Sigma molecular switch regulation with implications for an array of additional processes. As such, this project will explore a novel, systems-level gene regulatory control for global prokaryotic transcriptome reprogramming, advancing our basic knowledge of the molecular mechanism driving microbial adaption and environmental responses. We appreciate the support provided by NSF Grant 2137138 awarded by the Division Of Molecular and Cellular Bioscience. A big thank you to Dr. Glen Borchert, members of the Borchert Lab, the Department of Pharmacology, and the Frederick P. Whiddon College of Medicine for their collective efforts in supporting this project.