6206 Marsico Hall
The Tamayo Lab studies how facultative pathogenic bacteria adapt to disparate and changing extracellular conditions. Specifically, we are interested in a bacterial second messenger that transmits signals received at the cell surface to control a wide variety of adaptive responses. This signaling molecule, c-di-GMP, is ubiquitous in bacteria and regulates the switch between motile and non-motile lifestyles in many species. In many cases, the non-motile phase involves development of a microbial community called a biofilm. In some bacterial pathogens, c-di-GMP regulates virulence factor production as well.
C. difficile is a Gram-positive, spore-forming, obligate anaerobe that causes a spectrum of intestinal diseases. C. difficile diseases are among the most commonly acquired nosocomial infections in the developed world. Treatment of C. difficile infections costs more than $3 billion per year in the U.S. alone. C. difficile produces well-characterized cytotoxins that damage the intestinal epithelium, resulting in inflammation and diarrheal symptoms. Yet little is known about how this organism senses its entry into the host and adapts to the intestinal environment. We aim to determine if and how c-di-GMP influences C. difficile colonization of the host intestine and development of disease. We have generated tools for manipulating c-di-GMP levels in C. difficile and have identified numerous pathways regulated by c-di-GMP. These processes include flagellum-based swimming motility, cytotoxin production, pilus-mediated surface motility, and cell-cell adhesion, suggesting a fundamental role for c-di-GMP in the ability of C. difficile to colonize and cause disease in the intestine. We are currently investigating the molecular basis of c-di-GMP regulation of these various pathways and the impact of c-di-GMP signaling on C. difficile virulence. In addition, we are dissecting the c-di-GMP signaling pathway by evaluating the contribution of individual components (i.e., c-di-GMP synthases and hydrolases) to controlling c-di-GMP—regulated processes and by identifying the extracellular stimuli that influence intracellular c-di-GMP levels.