Timothy L. Yahr, Ph.D.
Ph.D., Medical College of Wisconsin, 1998 |
Associate Professor of Microbiology Campus address: 540B EMRB Mailing address: 431 Newton Rd. 540B Eckstein Medical Research Building Iowa City, IA 52242 Phone: 319-335-9688 Email: |
Role of the type III secretion system in the pathogenesis of Pseudomonas aeruginosa
My laboratory studies regulation of the Pseudomonas aeruginosa type III secretion system (T3SS). T3SS's are unique to Gram-negative bacteria and function to deliver toxins into eukaryotic host cells. The secretion machinery consists of ~30 proteins which span both the inner and outer membranes of the bacterial cell. Following contact of the bacterium with a eukaryotic cell, the type III machinery functions like a molecular syringe to inject toxins into the host cell. Expression of the P. aeruginosa T3SS is highly regulated and induced by at least two environmental cues; contact of the bacteria with eukaryotic cells and growth in the presence of low Ca2+ concentrations. In the absence of these cues, low amounts of the type III secretion channels are assembled within the cell membranes. The channels, however, are inactive and expression of the T3SS is repressed. Expression of the T3SS genes is coupled to type III secretory activity by a cascade of interacting regulatory proteins (ExsA, ExsD, ExsC, and ExsE). ExsA is an activator of type III gene transcription, ExsD binds ExsA to inhibit transcription, ExsC inhibits ExsD activity, and ExsE inhibits ExsC activity. The entire process is coupled to secretion by virtue of the fact that ExsE is a secreted substrate of the T3SS. Changes in the intracellular concentration of ExsE are thought to govern formation of the ExsC-ExsE, ExsC-ExsD, and ExsD-ExsA complexes. Whereas formation of the ExsC-ExsE complex allows ExsD to bind ExsA and transcription of the T3SS is repressed, formation of the ExsC-ExsD complex sequesters ExsD from ExsA and transcription of the T3SS is induced. The major efforts in my lab involve testing the above model and determining how this regulatory cascade interfaces with a number of additional regulatory mechanisms also controlling T3SS gene expression.
Additional information:
UI Carver College of Medicine Interview
Yahr Lab Home Page
Recent publications
Brutinel, E.D., and T.L. Yahr. 2008. Control of gene expression by
secretory activity. Curr Opin Microbiol 11:128-133.
Brutinel, E.D., C.A. Vakulskas, K.M. Brady, and T.L. Yahr. 2008.
Characterization of ExsA and of ExsA-dependent promoters required for
expression of the Pseudomonas aeruginosa type III secretion system. Mol
Microbiol 68:657-671.
Urbanowski, M.L., and T.L. Yahr. 2007. Translocation of ExsE into Chinese hamster ovary cells is required for transcriptional induction of the Pseudomonas aeruginosa type III secretion system. Infect Immun 75:4432-4439.
Yahr, T.L., and M.C. Wolfgang. 2006. Transcriptional regulation of the Pseudomonas aeruginosa type III secretion system. Mol Microbiol 62:631-640.