The presence or absence of flagellar structures in several pathogenic bacteria has been shown to be the etiologic agent for disease in these organisms. Flagellin gene expression in Bacillus subtilis, a non-pathogenic, soil-organism has been shown to be part of a regulon of genes under the control of an alternate sigma factor. A homologous regulon has been identified in several pathogenic and non-pathogenic organisms including Escherichia coli and Salmonella typhimurium, Campylobacter jejuni, Campylobacter coli, Caulobacter crescentus, Pseudomonas aeuriginosa, Rhizobium meliloti, and Vibrio cholerae. The overall objective of the proposed research is to better define the molecular mechanisms regulating flagellar gene expression in B. subtilis. The emphasis is on the genetic and molecular characterization of the SpoOK signal transduction cascade and its importance in controlling flagellin gene expression. The spoOK gene products form a membrane transport system that allows for the internalization of oligopeptides. This system has been proposed to be the most upstream component of signal transduction between the external environment and the initiation of sporulation and other post-exponential phenomena in B. subtilis. The proposed studies will not only provide additional information on an important signal transduction cascade, but will further define the regulation of flagellin gene expression in B. subtilis. This information will then facilitate a greater understanding of this process in pathogenic bacteria. We propose to study the SpoOK signal transduction cascade by 1) investigating the role of the spoOK gene products in regulating transcription of the flagellin gene; 2) delineating the environmental signals that affect flagellin expression; 3) determining the role of the KinA kinase, activated by the SpoOK signal, in regulating flagellin expression; and 4) identifying and characterizing cis acting elements required for regulation of flagellin gene expression by SpoOK-dependent signal transduction.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
5R15GM054342-02
Application #
2444901
Study Section
Special Emphasis Panel (ZRG5-MBC-1 (02))
Project Start
1996-07-01
Project End
1999-03-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
San Francisco State University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94132
Mirel, D B; Estacio, W F; Mathieu, M et al. (2000) Environmental regulation of Bacillus subtilis sigma(D)-dependent gene expression. J Bacteriol 182:3055-62