812 Talk: Regulation of virulence in Proteus mirabilis

Seminar Details
Friday, January 29, 2021 - 12:00pm to 1:00pm


Madison Fitzgerald
Ph.D. Candidate, Mobley Lab
Department of Microbiology & Immunology, University of Michigan Medical School


Zoom Meeting: https://umich-health.zoom.us/j/94468353155?pwd=N2F5c0NYZkdtUHFTUW9NbkJiU0RaZz09

Meeting ID: 944 6835 3155  Passcode: 340574


Urinary Tract Infections (UTIs) are common infections that represent a significant burden on health care systems worldwide. In 2006 alone, UTIs were the source of 11 million physician visits and cost the United States over $3.5 billion. A portion of these infections are Catheter-Associated UTIs (CAUTIs), accounting for up to 40% of hospital acquired infections globally. A major cause of CAUTIs is Proteus mirabilis, an understudied Gram-negative member of the Enterobacteriales order. Previous studies have used a mouse model of UTI to identify factors that contribute to fitness and virulence in the urinary tract. These datasets implicate transcriptional regulators, but there is much to learn about transcriptional networks in this species. Towards this end, I have developed the framework to employ Transcriptional Regulator Induced Phenotype (TRIP) screening to identify regulators that contribute to uropathogenesis. TRIP leverages a library of strains containing inducible expression constructs that each encode a single regulator.  Pools of these strains will be inoculated into the mouse model of UTI to assess comparative fitness. A systematic approach identified 232 putative transcriptional regulators in the HI4320 genome, only three of which have defined regulons. While the construct library is being generated, the designed expression system is being validated using a variety of techniques. These studies indicate that stable expression of regulators is not broadly toxic, the system is responsive to the inducer, and the constructs are carried by a stable vector. This project represents the first in vivo application of TRIP and will identify key regulators of uropathogenesis.