Vibrio cholerae causes the disease cholera and is a natural inhabitant of aquatic environments. Seasonal cholera outbreaks occur where the disease is endemic and can spread worldwide. V. cholerae's ability to form biofilms (i.e., matrix-enclosed, surface-associated communities) is crucial for its survival in aquatic habitats between epidemics and is advantageous for host-to-host transmission during epidemics. The objective of this proposal is to improve our understanding of biofilm matrix components, the mechanisms and regulation of biofilm formation, and their importance in the biology of V. cholerae.
In Aim 1, we will focus on understanding how biofilm matrix proteins RbmA, RbmC and Bap1 function. We will determine the molecular basis of RbmA and VPS interactions and determine molecular determinants and consequences of RbmA proteolysis. We will test whether RbmC and Bap1 bind to VPS and identify regions important for their function. We will also determine how these proteins contribute to the mechanical properties of biofilms, as well as the location of each matrix component by super resolution microscopy.
In Aim 2, we will determine the mechanism used by the regulatory proteins, VpsR and VpsT, in biofilm formation. We will identify sensor histidine kinases that phosphorylate VpsR, and determine phosphorylation dynamics of VpsR during biofilm development. We will also identify direct targets of VpsT and VpsR during biofilm formation and ascertain the contribution of VpsR and VpsT regulon members in V. cholerae transmission and dissemination into the environment. Clarifying the mechanisms of biofilm formation in V. cholerae will prove useful for the development of future strategies for controlling cholera epidemics, and facilitate identification of novel drug targets for combating the pathogen during infection.

Public Health Relevance

Biofilms, surface attached microbial communities, cause significant problems in environmental, industrial, and clinical settings. Vibrio cholerae, the causative agent of the disease cholera, forms naturally-occurring biofilms that are critical for environmental survival and the transmission of the pathogen. This proposal aims to improve our understanding of biofilm formation, which will allow us to define targets to combat this deadly pathogen in both intestinal and aquatic ecosystems, and also help in the development of tools for prediction and/or control of cholera epidemics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI114261-04
Application #
9293246
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Hall, Robert H
Project Start
2014-07-01
Project End
2019-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
4
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California Santa Cruz
Department
Public Health & Prev Medicine
Type
Schools of Arts and Sciences
DUNS #
125084723
City
Santa Cruz
State
CA
Country
United States
Zip Code
95064
Cheng, Andrew T; Zamorano-Sánchez, David; Teschler, Jennifer K et al. (2018) NtrC Adds a New Node to the Complex Regulatory Network of Biofilm Formation and vps Expression in Vibrio cholerae. J Bacteriol 200:
Joshi, Avatar; Kostiuk, Benjamin; Rogers, Andrew et al. (2017) Rules of Engagement: The Type VI Secretion System in Vibrio cholerae. Trends Microbiol 25:267-279
Fong, Jiunn Cn; Rogers, Andrew; Michael, Alicia K et al. (2017) Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms. Elife 6:
Conner, Jenna G; Zamorano-Sánchez, David; Park, Jin Hwan et al. (2017) The ins and outs of cyclic di-GMP signaling in Vibrio cholerae. Curr Opin Microbiol 36:20-29
Conner, Jenna G; Teschler, Jennifer K; Jones, Christopher J et al. (2016) Staying Alive: Vibrio cholerae's Cycle of Environmental Survival, Transmission, and Dissemination. Microbiol Spectr 4:
Teschler, Jennifer K; Zamorano-Sánchez, David; Utada, Andrew S et al. (2015) Living in the matrix: assembly and control of Vibrio cholerae biofilms. Nat Rev Microbiol 13:255-68
Ruhe, Zachary C; Townsley, Loni; Wallace, Adam B et al. (2015) CdiA promotes receptor-independent intercellular adhesion. Mol Microbiol 98:175-92