CB# 7290, 517 MEJ
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 unique to and ubiquitous in bacteria and regulates the switch between motile and non-motile lifestyles in many bacterial species. In many cases, the non-motile phase involves development of a microbial community called a biofilm. In some bacteria, including Vibrio cholerae described below, c-di-GMP regulates virulence factor production as well.
We study c-di-GMP signaling in two bacterial gastrointestinal pathogens- Vibrio cholerae and Clostridium difficile.
V. cholerae is a Gram-negative bacterium that causes the severe diarrheal disease cholera. There are an estimated 1-2 million cases of cholera every year, mainly in developing areas or when sanitation breaks down. Treatment consists of rehydration therapy, but when treatment is unavailable the mortality rate can exceed 50%. V. cholerae is a natural inhabitant of aquatic environments, including fresh and saline waters. Several groups have reported that V. cholerae persists in aquatic environments as biofilms attached to a variety of biotic surfaces. The ability of V. cholerae to produce a biofilm has been hypothesized to be protective for the bacteria both in the aquatic environment as well as in the human host, and biofilms are believed to serve as the reservoir of V. cholerae. We are interested in how V. cholerae orchestrates the dramatic changes in gene expression that occur as it transits between the aquatic and host environments. The secondary messenger c-di-GMP plays a key role in this transition between the environment and host. Many of the targets of transcriptional regulation by c-di-GMP have been uncovered, yet the mechanisms by which c-di-GMP regulates gene transcription are largely unknown. We aim to uncover these mechanisms and are examining the role of a riboswitch in directly sensing changing levels of c-di-GMP to regulate gene expression. Ultimately, by better understanding how V. cholerae maintains its dichotomous lifestyle, we will gain insight into how V. cholerae spurs epidemic as well as endemic disease.
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 in the U.S. alone. Yet little is known about how this organism senses its entry into the host and adapts to the intestinal environment. We are using C. difficile as a model organism to explore the roles of c-di-GMP in Gram-positive bacteria, in which c-di-GMP has been poorly studied. We have developed tools for manipulating c-di-GMP levels in C. difficile and have identified numerous pathways regulated by c-di-GMP, including motility and cell-cell adhesion. We are currently investigating the molecular basis of how c-di-GMP controls these various pathways.
Purcell EB, McKee RM, McBride SM, Waters CM and R Tamayo (2012) Cyclic diguanylate inversely regulates motility and aggregation in Clostridium difficile. Journal of Bacteriology.
Mudrak A and R Tamayo (2012) The Vibrio cholerae Pst2 phosphate transport system is upregulated in biofilms and contributes to biofilm-induced hyperinfectivity. Infection and Immunity. 80 (5):1794-802.
Mudrak B and R Tamayo (2011) Identifying new variables during infection: proximity to the host epithelium and epigenetic programs alter the expression of virulence factors in Vibrio cholerae. Frontiers in Cellular and Infection Microbiology. Vol 2, Article 42, p.1-2
Tamayo R, B Patimalla and A Camilli (2010) Growth in a biofilm induces a hyperinfectious phenotype in Vibrio cholerae. Infection and Immunity. 78:3560-9.
Pratt JT, R Tamayo and A Camilli (2010) Role of c-di-GMP in Vibrio cholerae virulence. The Second Messenger Cyclic Diguanylate. Eds. A Wolfe and K. Visick. ASM Press.
Martinez-Wilson HF, R Tamayo, AD Tischler, DW Lazinski and A Camilli (2008) The Vibrio cholerae hybrid sensor kinase VieS contributes to motility and biofilm regulation by altering cyclic diguanylate level. Journal of Bacteriology. 190:6439-6447.
Tamayo R, S Schild, JT Pratt and A Camilli (2008) Role of cyclic d-GMP during El Tor biotype Vibrio cholerae infection: Characterization of the in vivo induced cyclic-di-GMP phosphodiesterase CdpA. Infection and Immunity. 76:1617-27.
Tamayo R, JT Pratt and A Camilli (2007) Cyclic di-GMP and regulation of bacterial pathogenesis. Annual Review of Microbiology. 61:131-148.
Benach J, SS Swaminathan, R Tamayo, SK Handelman, E Folta-Stogniew, JE Ramos, F Forouhar, H Neely, J Seetharaman, A Camilli and JF Hunt (2007) The structural basis of cyclic diguanylate signal transduction by PilZ domains. EMBO Journal. 26:5153-5166.
Schild S, R Tamayo, EJ Nelson, F Qadri, SB Calderwood and A Camilli (2007) Genes induced late in infection increase fitness of Vibrio cholerae after release into the environment. Cell Host Microbe. 2:264-277.
Pratt JT, R Tamayo, AD Tischler and A Camilli (2007) PilZ domain proteins bind cyclic diguanylate and regulate diverse processes in Vibrio cholerae. Journal of Biological Chemistry. 282:12860-70.
Tamayo R, AD Tischler and A Camilli (2005) The EAL domain protein VieA is a cyclic diguanylate phosphodiesterase. Journal of Biological Chemistry. 280:33324-30.
Tamayo R, et al. (2005) Identification of cptA, a PmrA-regulated locus required for phosphoethanolamine modification of the Salmonella enterica serovar Typhimurium LPS core. Journal of Bacteriology 187:3391-9.
Tamayo R, AM Prouty and JS Gunn (2005) Identification and functional analysis of Salmonella enterica serovar Typhimurium PmrA-regulated genes. FEMS Immunology and Medical Microbiology. 43:249-58.
Tamayo R, AC Portillo and JS Gunn (2004) Mechanisms of Bacterial Resistance to Antimicrobial Peptides. Mammalian Antimicrobial Peptides, Advances in Molecular and Cellular Microbiology Series. Eds. DA Devine and REW Hancock. Cambridge University Press. 323-348.
Tamayo R, SR Ryan, AJ McCoy and JS Gunn (2002) Identification and genetic characterization of PmrA-regulated genes and genes involved in polymyxin B resistance in Salmonella enterica serovar Typhimurium. Infection and Immunity. 70:6770-6778.