Bacterial pathogenesis; virulence of uropathogenic bacterial species
My laboratory is interested in the molecular mechanisms of bacterial pathogenesis. We are studying virulence mechanisms of uropathogenic Escherichia coli and Proteus mirabilis that cause urinary tract infection.
The urinary tract is susceptible to infection by bacteria. Indeed, urinary tract infection is one of the most common bacterial infections of humans. The most common bacterium that infects the urinary tract of healthy individuals is Escherichia coli. On the other hand, in patients who have urinary catheters in place, Proteus mirabilis often infects the bladder and causes stones to form there. Both of these bacteria can either stick to the surface of the bladder or swim up to the kidneys. But they should not do both. We are studying the molecular mechanism by which these bacteria decide to stick or decide to swim. Understanding how these bacteria reciprocally regulate motility and adherence will allow us to combat these infections that each year costs the United States nearly 3 billion dollars to treat.
One strategy to prevent infections is to develop a mucosal vaccine against antigens that are expressed in vivo, present on the bacterial surface, specific to uropathogenic strains, and antigenic. We are using a large-scale selection process that incorporates bioinformatic, genomic, transcriptomic, and proteomic screens to identify, in an unbiased manner, potential vaccine candidates. Using a murine model of ascending urinary tract infection, we are testing these antigens for the ability to protect against bladder and kidney infection by uropathogenic strains of E. coli. In addition, we are identifying immunological correlates of protection.
Garcia, Erin C., Ariel R. Brumbaugh, and Harry L.T. Mobley. 2011. Redundancy and specificity of Escherichia coli iron acquisition systems during urinary tract infection. Infect. Immun. 79:1225-1235.
Sahl, Jason W., Amanda Lloyd, Julia Redman, Thomas A. Cebula, Richard Colgan, Michael S. Donnenberg, David P. Wood, Harry L.T. Mobley, and David A. Rasko. 2011. Genomic characterization of asymptomatic Escherichia coli isolated from the neobladder. Microbiology 157:1088-1102.
Vigil, Patrick D., Christopher J. Alteri, and Harry L.T. Mobley. 2011. Identification of in vivo induced antigens including a RTX family exoprotein required for uropathogenic Escherichia coli virulence. Infect Immun. 79:2335-2344.
Mosberg, Joshua A., Alejandra Yep, Timothy C. Meredith, Sara Smith, Tod P. Holler, Harry L.T. Mobley and Ronald W. Woodard. 2011. A unique arabinose 5-phosphate isomerase found within a genomic island associated with uropathogenicity of Escherichia coli CFT073. J. Bacteriol. 193:2981-2988.
Vigil, Patrick D., Ann E. Stapleton, James R. Johnson, Thomas M. Hooton, Andrew P. Hodges, Yongqun He, and Harry L.T. Mobley. 2011. Presence of putative repeat-in-toxin (RTX) gene tosA of Escherichia coli predicts successful colonization of the urinary tract. mBio 2:e00066-11.
Pearson, Melanie M., Alejandra Yep, Sara N. Smith, and Harry L.T. Mobley. 2011. Transcriptome of Proteus mirabilis in the murine urinary tract: Virulence and nitrogen assimilation gene expression. Infect. Immun. 79:2619-2631.
Flannery, Erika L., Samantha M. Antczak, and Harry L.T. Mobley. 2011. Self-transmissibility of the Integrative and Conjugative Element ICEPm1 Between Clinical Isolates Requires a Functional Integrase, Relaxase and Type IV Secretion System. J. Bacteriol. 193:4104-4112.
Alteri,Christopher J., Jonathon R. Lindner, Daniel J. Reiss, Sara N. Smith, and Harry L.T. Mobley, 2011. A broadly conserved regulator links pathogen virulence and membrane potential. Molec. Microbiol. 82:145-163.
Spurbeck, Rachel R., Ann E. Stapleton, James R. Johnson, Seth T. Walk, Thomas M. Hooton, and Harry L.T. Mobley. 2011. Fimbrial Profiles Predict Virulence of Uropathogenic E. coli Strains: Contribution of Ygi and Yad Fimbriae. Infect. Immun. 79:4753-4763 [Selected for Spotlight: Articles of significant interest]
Flannery, Erika L., Linda Wang, Sebastian Zoellner, Betsy Foxman, Harry L.T. Mobley, and Lona Mody. 2011. Wounds, Functional Disability and Indwelling Devices are Associated with Co-Colonization by MRSA and VRE in southeastern Michigan. Clin Infect Dis 53:1215-1222.
Reiss, Daniel J. and Harry L.T. Mobley. Determination of the Target Sequence bound by PapX, a Repressor of Bacterial Motility, in the flhD Promoter using SELEX and High-Throughput Sequencing. 2011. J. Biol. Chem. 286:44726-44738.
Vigil, Patrick D., Travis Wiles, Michael D Engstrom, Lev Prasov, Matthew A. Mulvey, and Harry L.T. Mobley. The repeat-in-toxin (RTX) family member TosA mediates adherence of uropathogenic Escherichia coli and survival during bacteremia. 2012. Infect. Immun. 80:493-505 [selected for Faculty of 1000].
Alteri, Christopher J. and Harry L.T. Mobley. 2012 Escherichia coli physiology and metabolism dictates adaptation to diverse host microenvironments. Curr. Op. Microbiol. 15:3-9.
Walters, Matthew S., M. Chelsea Lane, Patrick D. Vigil, Sara N. Smith, Seth T. Walk, and Harry L.T. Mobley. 2012. Kinetics of uropathogenic Escherichia coli metapopulation movement during urinary tract infection. mBio 3:e00303-11.