The bacterial flagellum is a self-assembling, proton-powered rotary nanomachine that drives motility, allowing chemotaxis. It contains a dedicated type III secretion (T3S) apparatus. Homologous T3S systems are used by pathogenic bacteria to effect virulence, underlying many bacterial diseases such as typhoid fever and bacterial dysentery. Using Salmonella enterica as a model system, we will investigate dynamic interactions among flagellar proteins that allow membrane translocation of export substrates through use of molecular biology, genetics and biochemical techniques including optical biosensing.
The specific aims are to complete a kinetic survey of interactions among export apparatus proteins using optical biosensing as the primary tool, to examine higher-than-pairwise interactions that better reflect in vivo dynamics and to further the development of an in vitro T3S assay. Eventual development of an in vitro export assay will be of tremendous significance because it would allow us to examine hypotheses addressing T3SS function currently out of reach. Since the flagellar export apparatus is highly similar to virulence T3S systems, the project will contribute significantly to our understanding of bacterial pathogenesis. AREA program goals of enhancing the research environment and exposing students to meritorious research will be well-served by this project.

Public Health Relevance

Assembly of the bacterial flagellum occurs by a process called Type III Secretion that is common to many bacterial diseases. Quantitative analysis of protein-protein interactions and development of an assay to examine secretion in vitro will enable description in detail of the molecular events of flagellar assembly. Success in this research will allow us to better understand the molecular events that occur in pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
3R15GM080701-02S1
Application #
8394244
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Flicker, Paula F
Project Start
2007-08-01
Project End
2014-07-31
Budget Start
2011-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$22,927
Indirect Cost
$6,409
Name
Kennesaw State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
627758923
City
Kennesaw
State
GA
Country
United States
Zip Code
30144
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