Bacterial pathogenesis; virulence of uropathogens and Helicobacter pylori

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.

Alamuri, Praveen and Harry L.T. Mobley. 2008. A Novel Autotransporter of Uropathogenic Proteus mirabilis is both a Cytotoxin and an Agglutinin. Molec. Microbiol. 68:997-1017.

Simms, Amy N. and Harry L.T. Mobley. 2008. Multiple genes repress motility in uropathogenic Escherichia coli constitutively expressing type 1 fimbriae. J. Bacteriol. 190:3747-3756. [selected for ASM Journal Highlights]

Pearson, Melanie M., Mohammed Sebaihia, Carol Churcher, Michael A. Quail, Zahra Abdellah, Claire Arrosmith, Becky Atkin, Tracey Chillingworth, Heidi Hauser, Kay Jagels, Sharon Moule, Karen Mungall, Halina Norbertczak, Ester Rabbinowitsch, Danielle Walker, Sally Whithead, Nicholas R. Thomson, Philip N. Rather, Julian Parkhill, and Harry L. T. Mobley. 2008. The Complete genome sequence of Proteus mirabilis, a master of both adherence and motility. J. Bacteriol. 190:4027-4037.

Pearson, Melanie, M. and Harry L.T. Mobley. 2008. Repression of motility during fimbrial expression: identification of 14 mrpJ gene paralogues in Proteus mirabilis. Molec. Microbiol. 69:548-558. 

Himpsl, Stephanie D., Virginia Lockatell, J. Richard Hebel, David E. Johnson, and Harry L.T. Mobley. 2008. Identification of Virulence Determinants in Uropathogenic Proteus mirabilis using Signature-Tagged Mutagenesis. J. Med. Microbiol. 57:1068-1078.

Nielubowicz, G.R. Sara N Smith, and Harry L.T. Mobley. 2008. Outer Membrane Antigens of the Uropathogen Proteus mirabilis Recognized by the Humoral Response during Experimental Murine Urinary Tract Infection. Infect. Immun. 76:4222-4231.

Simms, Amy N. and Harry L.T. Mobley. 2008. PapX, a P Fimbrial-Encoded Inhibitor of Motility in Uropathogenic Escherichia coli. Infect. Immun. 76:4833-4841.

Alamuri, P., K.A Eaton,.S.N. Smith, S.D. Himpsl, and H.L.T. Mobley. 2009. Vaccination with Proteus Toxic Agglutinin, a Hemolysis-Independent Cytotoxin In vivo, Protects Agains Proteus mirabilis UTI. Infect. Immun. 77:632-641.

Hagan E.C. and Harry L.T. Mobley. 2009. Haem acquisition is facilitated by a novel receptor Hma and required by uropathogenic Escherichia coli for kidney infection. Molec. Microbiol. 71:79-91. 

Lane*, M.C., X. Li*, M.M. Pearson*, A.N. Simms*, and H.L.T. Mobley. 2009. Oxygen-limiting conditions enrich for fimbriate bacteria of uropathogenic Proteus mirabilis and Escherichia coli. J. Bacteriol. 191:1382-1392. [*contributed equally].

Buckles, Eric., Xiaolin. Wang, M.Chelsea Lane, C.Virginia Lockatell, David E. Johnson, Harry L.T. Mobley, Michael S. Donnenberg. 2009. The role of K2 capsule in Escherichia coli urinary tract infection and serum resistance. J. Infect. Dis. 199:1689-1697.

O'May, G.A., S.M. Jacobsen, M. Longwell, P. Stoodley, H.LT. Mobley, and M.E. Shirtliff. 2009. The-affinity phosphate transporter Pst in Proteus mirabilis HI4320 and its importance in biofilm formation. Microbiology 155:1523-1535.

Lloyd, Amanda L., Tiffany A. Henderson, Patrick Vigil, Harry L.T. Mobley. 2009. Genomic Islands of Uropathogenic Escherichia coli Contribute to Virulence. J. Bacteriol. 191:3469-3481. 

Alteri, C., S. Smith, and Harry L.T. Mobley. 2009. Fitness of Escherichia coli during Urinary Tract Infection Requires Gluconeogenesis and the TCA Cycle PLoS Pathogens 5:e1000448.