Each year 2-5 million people suffer from the diarrheal disease cholera. This disease is caused by V. cholerae, a mostly marine bacterium that also thrives in the human gastrointestinal (GI) tract and in fresh water environments in cholera endemic areas. Upon ingestion by the host, V. cholerae colonizes the small intestine, multiplies extensively, and secretes cholera toxin. The toxin initiates a signal transduction cascade in the host that leads to a massive efflux of fluid into the intestinal lumen; this ultimately (in regions with poor sanitation systems) releases V. cholerae back into the environment. Thus, the life cycle of V. cholerae involves repetitive transitions between aquatic environments and the host GI tract (Figure 1). It remains unclear, however, how the bacteria are able to rapidly adapt to and multiply within these varying niches. Moreover, cholera represents a paradigm for complex, ecological bacterial diseases. Understanding the entire life cycle of V. cholerae, specifically how it modulates its physiology to adapt to different environments, is critical to enhancing our ability to combat infectious diseases as a whole.
The long-term goal of my research is to understand how V. cholerae adapts to different carbon sources and thereby persists in its environmental reservoirs. Specifically, the objective of this project is to identify and characterize molecular mechanisms by which V. cholerae synchronizes its physiology with available carbon sources. This research is led by a central hypothesis that V. cholerae relies on a suite of small regulatory RNAs (sRNAs) to adapt to changing environmental conditions. There is growing evidence that in many bacteria, including V. cholerae, sRNA regulatory circuits modulate metabolic and behavioral processes. Thus, to truly understand how V. cholerae is able to adjust its physiology for long-term persistence, the multiple sRNAs involved must be identified and characterized. Toward this end, I am actively researching the biological roles of novel RNAs that I previously identified in V. cholerae, focusing on sRNAs that may affect carbon metabolism in the pathogen. I expect that my research will identify molecular components of V. cholerae that allow it to adapt and persist in its natural environments.