Cholera is a severe epidemic diarrheal disease caused by the gram-negative aquatic bacterium Vibrio cholerae. As is true for most bacterial pathogens, attachment to biotic surfaces such as the exoskeletae of copepods and the intestinal epithelium is critical to survival of V. cholerae. V. cholerae can either attach to surfaces as a monolayer, which is defined by the presence of cell-surface adhesion without interbacterial adhesion, or as a biofilm, which is defined by the presence of cell-surface and interbacterial adhesions. In the previous funding period of this grant, we focused on defining the environmental signals, genetic requirements, and gene transcription profiles that defined the V. cholerae monolayer and biofilm. During the next funding period, we propose to investigate three observations made during the previous funding period. These are (i) monosaccharides are strong inducers of biofilm development and transcription of genes encoding monosaccharide transporters is co-regulated with biofilm exopolysaccharide synthesis gene transcription, (ii) secreted proteins play a role in biofilm matrix formation, and (iii) transcription of a putative undecaprenyl pyrophosphate phosphatase is regulated similarly to that of biofilm exopolysaccharide synthesis genes and is required for biofilm formation. The relevant specific aims for this funding period are: 1) To investigate regulation of surface-associated growth in glucose-rich environments and to define its relevance to survival within the host gastrointestinal tract. 2) To characterize the functions of proteinaceous components of the Vibrio cholerae biofilm matrix. 3) To study the role of an undecaprenyl pyrophosphate phosphatase in V. cholerae biofilm matrix synthesis.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Bacterial Pathogenesis Study Section (BACP)
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Hall, Robert H
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Children's Hospital Boston
United States
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Pickering, Bradley S; Lopilato, Jane E; Smith, Daniel R et al. (2014) The transcription factor Mlc promotes Vibrio cholerae biofilm formation through repression of phosphotransferase system components. J Bacteriol 196:2423-30
Ymele-Leki, Patrick; Houot, Laetitia; Watnick, Paula I (2013) Mannitol and the mannitol-specific enzyme IIB subunit activate Vibrio cholerae biofilm formation. Appl Environ Microbiol 79:4675-83
Pickering, Bradley S; Smith, Daniel R; Watnick, Paula I (2012) Glucose-specific enzyme IIA has unique binding partners in the vibrio cholerae biofilm. MBio 3:e00228-12
Ymele-Leki, Patrick; Cao, Shugeng; Sharp, Jared et al. (2012) A high-throughput screen identifies a new natural product with broad-spectrum antibacterial activity. PLoS One 7:e31307
Absalon, Cedric; Van Dellen, Katrina; Watnick, Paula I (2011) A communal bacterial adhesin anchors biofilm and bystander cells to surfaces. PLoS Pathog 7:e1002210
Houot, Laetitia; Chang, Sarah; Pickering, Bradley S et al. (2010) The phosphoenolpyruvate phosphotransferase system regulates Vibrio cholerae biofilm formation through multiple independent pathways. J Bacteriol 192:3055-67
Houot, Laetitia; Chang, Sarah; Absalon, Cedric et al. (2010) Vibrio cholerae phosphoenolpyruvate phosphotransferase system control of carbohydrate transport, biofilm formation, and colonization of the germfree mouse intestine. Infect Immun 78:1482-94
Karatan, Ece; Watnick, Paula (2009) Signals, regulatory networks, and materials that build and break bacterial biofilms. Microbiol Mol Biol Rev 73:310-47
Van Dellen, Katrina L; Houot, Laetitia; Watnick, Paula I (2008) Genetic analysis of Vibrio cholerae monolayer formation reveals a key role for DeltaPsi in the transition to permanent attachment. J Bacteriol 190:8185-96
Houot, Laetitia; Watnick, Paula I (2008) A novel role for enzyme I of the Vibrio cholerae phosphoenolpyruvate phosphotransferase system in regulation of growth in a biofilm. J Bacteriol 190:311-20

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