Vibrio cholerae, the etiological agent of the severe diarrheal disease cholera, is an enteric pathogen that can be found in aquatic ecosystems when not colonizing the human gastrointestinal tract. Under adverse environmental conditions, V. cholerae is capable of entering dormant states that increase its survival during these ecological fluctuations. In these states, V. cholerae slows its metabolic activity and exhibits drastically altered gene expression and morphology. Stressors that lead to entry into these states vary from nutrient limitation, suboptimal pH, or antimicrobials. Cells in these dormant states are highly resistant to antimicrobials and cannot be detected using standard microbiological techniques which poses major public health challenges such as food or water contamination. In V. cholerae, proteolysis of virulence regulator ToxR has been identified to be required for entry into a dormant state called viable but nonculturable (VBNC) under nutrient limitation and alkaline pH mediated by the sigma-E stress response. However, the mechanisms that lead to the initiation of this cascade remain unknown. The stringent response is another mechanism involved in mediating bacterial survival during late stationary phase. The stringent response involves the alarmone (p)ppGpp, which acts at the level of transcription to inhibit cellular processes that consume significant resources and activate genes responsible for biosynthetic processes. RelA is one enzyme responsible for the synthesis of (p)ppGpp, which in turn activates transcription of RpoE, suggesting a potential connection with ToxR proteolysis. Therefore, the aim of this study is to define the role of RelA in dormancy and ToxR proteolysis in V. cholerae. Our results show that RelA alone is not sufficient to control dormancy and ToxR proteolysis in V. cholerae. Nonetheless, another regulator (SpoT) is also associated with (p)ppGpp synthesis, indicating that other stringent response-associated mechanisms might be involved in ToxR proteolysis.
Bachelor of Science (B.S.)
College of Medicine
Burnett School of Biomedical Sciences
Malaussena, Zachary J., "Role of RelA in Dormancy and ToxR Proteolysis in Vibrio cholerae" (2021). Honors Undergraduate Theses. 918.