Matt Mulvey, Ph.D.

Matt Mulvey, Ph.D.


Scholarly Emphasis: Bacterial Pathogenesis

My lab is focused on understanding the survival and virulence strategies employed by a group of important bacterial pathogens collectively known as Extraintestinal Pathogenic Escherichia coli, or ExPEC. These bacteria can efficiently colonize the intestinal tract like commensal strains, but have the added capacity to disseminate and cause disease in other host niches, including the blood, central nervous system, and the urinary tract. Subsets of ExPEC known as Uropathogenic E. coli (UPEC) are the primary cause of urinary tract infections (UTIs), which rank among the most common of infectious diseases worldwide. These bacteria act as opportunistic invasive pathogens capable of entering host epithelial cells within the urinary tract where they can either rapidly multiply or alternatively persist in a more quiescent state for days to many weeks. We, and others, hypothesize that intracellular reservoirs of UPEC may contribute to the often chronic and recurrent nature of UTIs. ExPEC strains related to UPEC can have a broad host range and display a remarkable ability to adapt to widely varying environmental conditions, often facing nutrient limitations, antibiotics, and aggressive host defense mechanisms. Using genetics, microscopy, biochemistry, global gene expression analysis and molecular biology techniques coupled with cell culture, mouse, and zebrafish infection model systems, we are working to delineate both bacterial and host factors that control the ability of ExPEC to colonize and persist within diverse host environments ranging from the urinary tract to the blood and the gut. Specific goals of this research include:

1. Defining the mechanisms by which ExPEC invades, traffics, multiplies, and persists within host cells and tissues.

2. Identifying and functionally defining bacterial fitness and virulence factors, including small regulatory RNAs, that enable ExPEC isolates to resist the multitude of environmental stresses encountered during the course of an infection.

3. Determining how ExPEC-associated toxins and other virulence factors modulate and hijack host signaling events, including host cell death, survival, and inflammatory pathways.

Selected Publications

  • 1. Barber AE, Norton JP, Spivak AM, and Mulvey MA (2013). Urinary Tract Infections: Current and Emerging Management Strategies. Clin Infect Dis 57:719-724.
  • 2. Wiles TJ, Norton JP, Russell CW, Dalley BK, Fischer KF, and Mulvey MA (2013). Combining Quantitative Genetic Footprinting and Trait Enrichment Analysis to Identify Fitness Determinants of a Bacterial Pathogen. PLOS Genetics 9(8):e1003716. ** see associated web site:
  • 3. Debnath I, Barber AE, Dhakal BK, Kulesus RR, Norton JP, and Mulvey MA (2012). The Cpx Stress Response System Potentiates the Fitness and Virulence of Uropathogenic Escherichia coli. Infect Immun 81:1450-1459.
  • 4. Wiles TJ, Norton JP, Smith SN, Lewis AJ, Mobley HLT, Casjens SR, and Mulvey MA (2013). A Phyletically Rare Gene Promotes the Niche-specific Fitness of an E. coli Pathogen during Bacteremia. PLOS Pathogens 9(2):e1003175.
  • 5. Wiles TJ and Mulvey MA (2013). The RTX Pore-forming Toxin α-Hemolysin of Uropathogenic Escherichia coli: Progress and Perspectives. Future Microbiol. 8(1):73-84.
  • 6. Donovan GT, Norton JP, Bower JM, and Mulvey MA (2013). Adenylate Cyclase and the cAMP Receptor Protein (CRP) Modulate the Resistance and Virulence Capacity of Uropathogenic Escherichia coli. Infect Immun. 81(1):249-258.
  • 7. Jordan JP and Mulvey MA (2012). Toxin-Antitoxin Systems are Important for Niche-Specific Colonization and Stress Resistance of Uropathogenic Escherichia coli. PLOS Pathogens 8(10):e1002954.
  • 8. Dhakal BK and Mulvey MA (2012). The UPEC Pore Forming Toxin α-Hemolysin Triggers Proteolysis of Host Proteins to Disrupt Cell Adhesion, Inflammatory and Survival Pathways. Cell Host Microbe 11:58-69.
  • 9. Blango MG and Mulvey MA (2010). Persistence of uropathogenic Escherichia coli in the face of multiple antibiotics. Antimicrobiol Agents Chemother 54(5):1855-63.
  • 10. Wiles TJ, Bower JM, Redd MJ, Mulvey MA (2009). Use of zebrafish to probe the divergent virulence potentials and toxin requirements of extraintestinal pathogenic Escherichia coli. PLOS Pathogens, 5(12):e1000697.
  • 11. Bower JM, Gordon-Ragaas, HB, Mulvey MA (2009). Conditioning of uropathogenic Escherichia coli for enhanced colonization of the host. Infect Immun 77(5): 2104-2112.
  • 12. Dhakal BK and Mulvey MA (2009). Uropathogenic Escherichia coli invade host cells via an HDAC6-modulated microtubule-dependent pathway. J Biol Chem 284(1): 446-454.
  • 13. Eto ES, Gordon HB, Dhakal DK, Jones TA, and Mulvey MA (2008). Clathrin, AP-2, and the NPXY-binding subset of alternate endocytic adaptors facilitate FimH-mediated bacterial invasion of host cells. Cell Microbiol 10(12): 2553-2567.
  • 14. Kulesus RR, Diaz-Perez K, Slechta ES, Eto DS, and Mulvey MA (2008). Impact of the RNA chaperone Hfq on the fitness and virulence potential of uropathogenic Escherichia coli. Infect Immun 76(7):3019-3026.
  • 15. Wiles TJ, Dhakal BK, Eto DS, and Mulvey MA (2008). Inactivation of host Akt/protein kinase B signaling by bacterial pore-forming toxins. Mol Biol Cell, 19(4):1427-1438.
  • 16. Eto DS, Jones TA, Sunbdsbak JL and Mulvey MA (2007). Integrin-mediated invasion of host cells by type 1-piliated uropathogenic Escherichia coli. PLOS Pathogens, 3(7):e100.
  • 17. Eto DS, Sundsbak JL, Mulvey MA (2006). Actin-gated intracellular growth and resurgence of uropathogenic Escherichia coli. Cell Microbiol 8:704-717.
  • All Publications: Click Here

Professional Education

  • B.S., 1990, University of Texas at Austin, Biological Sciences (1988–1989, Molecular Biology); University of Texas at El Paso (1986–1988).
  • Ph.D., December, 1995, University of Texas at Austin, Biological Sciences (Virology).
  • Postdoctoral Fellowships:12/95 – 09/1996: Biomedical Centre, Uppsala, Sweden; 09/96 – 01/2001: Washington University School of Medicine, St. Louis, Department of Molecular Microbiology.