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Director of Graduate StudiesProfessor of Microbiology
Office: 540B Eckstein Medical Research Building431 Newton RdIowa City, IA 52242
Lab: 540 Eckstein Medical Research Building431 Newton RdIowa City, IA 52242
Email: firstname.lastname@example.orgWeb: Yahr Lab WebsiteWeb: Carver College of Medicine InterviewWeb: Google Scholar Page
BS, Biology, University of Wisconsin-Stevens PointMS, Microbiology, Medical College of WisconsinPhD, Microbiology, Medical College of Wisconsin
Post Doctorate, Biochemistry, Dartmouth Medical School
Department of Microbiology Graduate ProgramInterdisciplinary Graduate Program in Translational BiomedicineMedical Scientist Training Program
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.
Center for Biocatalysis and BioprocessingCenter for Gene Therapy of Cystic Fibrosis and other Genetic Diseases
Primary and Secondary Sequence Structure Requirements for Recognition and Discrimination of Target RNAs by Pseudomonas aeruginosa RsmA and RsmF.
2016 August 25. 198(18):2458-69.
Vfr Directly Activates exsA Transcription To Regulate Expression of the Pseudomonas aeruginosa Type III Secretion System.
2016 April 14. 198(9):1442-50.
Van Bambeke F.
Inhibition of the Injectisome and Flagellar Type III Secretion Systems by INP1855 Impairs Pseudomonas aeruginosa Pathogenicity and Inflammasome Activation.
J Infect Dis.
2016. Epub ahead of print.
Inhibition of Pseudomonas aeruginosa ExsA DNA-Binding Activity by N-Hydroxybenzimidazoles.
Antimicrob Agents Chemother.
2015 November 16. 60(2):766-76.
Regional Isolation Drives Bacterial Diversification within Cystic Fibrosis Lungs.
Cell Host Microbe.
2015 September 9. 18(3):307-19.
The RNA helicase DeaD stimulates ExsA translation to promote expression of the Pseudomonas aeruginosa type III secretion system.
2015 August. 197(16):2664-74.
Secretion of Flagellar Proteins by the Pseudomonas aeruginosa Type III Secretion-Injectisome System.
2015 June 15. 197(12):2003-11.
Self-association of ExsA is required for occupation of adjacent binding sites on Pseudomonas aeruginosa type III secretion system promoters.
2014 October. 196(20):3546-55.
The AlgZR Two-Component System Recalibrates the RsmAYZ Posttranscriptional Regulatory System To Inhibit Expression of the Pseudomonas aeruginosa Type III Secretion System.
2014 January. 196(2):357-66.
Schesser Bartra S,
ExsA and LcrF recognize similar consensus binding sites, but differences in their oligomeric state influence interactions with promoter DNA.
2013 December. 195(24):5639-50.
Date Last Modified: 10/04/2016 -
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