Cholera is a severe epidemic diarrheal disease caused by the gram-negative aquatic bacterium Vibrio cholerae. Attachment to biotic surfaces in a multi-layered structure known as a biofilm is critical to the survival and virulence of bacterial pathogens such as V. cholerae. Biofilm formation is viewed as a developmental process. In the first stage of this process, the bacterium forms a monolayer on the surface. Formation of a monolayer depends on cell-surface interactions. When cell-cell interactions are enabled, the monolayer develops into a multi-layered biofilm. During the previous funding period of this grant, we focused on defining the environmental signals, genetic requirements, and gene transcription profiles of the V. cholerae monolayer and biofilm.
The Specific Aims of this proposal arise from three discoveries made during the previous funding period and are as follows: 1) To investigate regulation of surface-associated growth in glucose rich environments and to define its relevance to survival within the host gastrointestinal tract. Observation: Glucose specifically regulates the entry of biofilm-associated cells into the stationary phase of growth. 2) To characterize the proteinaceous components of the Vibrio cholerae biofilm matrix. Observation: Two putative lectins are required for V. cholerae biofilm formation. 3) To study the role of an undecaprenyl pyrophosphate phosphatase in V. cholerae biofilm matrix synthesis. Observation: A putative undecaprenyl pyrophosphate phosphatase is specifically required for biofilm formation but not cell growth.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
High Priority, Short Term Project Award (R56)
Project #
2R56AI050032-07
Application #
7468895
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
Hall, Robert H
Project Start
2007-08-01
Project End
2009-05-21
Budget Start
2007-08-01
Budget End
2009-05-21
Support Year
7
Fiscal Year
2007
Total Cost
$380,250
Indirect Cost
Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115
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