Matthew A. Mulvey, PhD

Research Interests

  • Microbial Pathogenesis
  • Cell Biology
  • Bacteriology

Languages

  • English

Academic Information

  • Departments: Pathology - Professor
  • Divisions: Microbiology and Immunology

Academic Office Information

  • 801-581-5967
  • Emma Eccles Jones Medical Research Building
    Pathology
    15 N Medical Dr E, Room: 2520
    Salt Lake City, UT

Email: matthew.mulvey@path.utah.edu

Research Statement

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 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. In humans, ExPEC can efficiently colonize the gastrointestinal tract like commensal strains, but have the added capacity to disseminate and cause disease in other host niches, including the bloodstream, central nervous system, and the urinary tract. Infections caused by ExPEC are among the most common and costly on the planet. Making matters worse is the recent global dissemination and expansion of multidrug-resistant ExPEC strains that cannot be treated with frontline antibiotics.

We are working to delineate both bacterial and host factors that control the ability of ExPEC to colonize and persist within diverse host environments, with a major goal being the development of improved anti-bacterial therapeutics. This research utilizes genetics, microscopy, biochemistry, global gene expression analysis, and molecular biology techniques coupled with cell culture, mouse, and zebrafish infection model systems. Specific goals of this research include:

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

2. Identify and functionally define bacterial fitness and virulence factors, including small regulatory RNAs and other regulators, 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.

4. Develop new therapeutics and diagnostic tools to better manage and prevent urinary tract infections (UTI), sepsis, and other infections caused by ExPEC and related pathogens.

Education History

Type School Degree
Postdoctoral Fellowship Washington University School of Medicine
Bacterial Pathogenesis
Postdoctoral Fellow
Postdoctoral Fellowship Biomedical Centre
Crystallography
Postdoctoral Fellow
Doctoral Training University of Texas at Austin
Cell Research Institute, Biological Sciences, Virology
Ph.D.
Undergraduate University of Texas at Austin
Molecular Biology
B.S.
Undergraduate University of Texas at El Paso
Biology

Global Impact

Education History

Type School Degree Country
Postdoctoral Fellowship Biomedical Centre
Crystallography
Postdoctoral Fellow Sweden

Career

Institution Description Country
Biomedical Centre Postdoctoral Researcher Sweden

Selected Publications

Journal Article

  1. Biswas S, McCullough BS, Ma ES, LaJoie D, Russell CW, Brown DG, Round JL, Ullman KS, Mulvey MA, Barrios AM (2017). Dual colorimetric and fluorogenic probes for visualizing tyrosine phosphatase activity. Chem Commun (Camb), 53(14), 2233-2236.
  2. Erman A, Hergouth VK, Blango MG, Kos MK, Mulvey MA, Verani P (2017). Repeated treatments with chitosan in combination with antibiotics completely eradicate uropathogenic Escherichia coli from infected mouse urinary bladders. J Infect Dis, 216(3), 375-381.
  3. Wambaugh MA, Shakya VPS, Lewis AJ, Mulvey MA, Brown JCS (2017). High-throughput identification and rational design of synergistic small molecule pairs for combating and bypassing antibiotic resistance. PLoS Biol, 15(6), e2001644.
  4. Russell CW, Richards AC, Chang AS, Mulvey MA (2017). The rhomboid protease GlpG promotes the persistence of extracellular pathogenic Escherichia coli within the gut. Infect Immun, 85(6), e00866-16.
  5. Kjelstrup CK, Barber AE, Norton JP, Mulvey MA, LAbe-Lund TM (2017). Escherichia coli O78 isolated from septicemic lambs shows high pathogenicity in a zebrafish model. Vet Res, 48(1), 3.
  6. Barber AE, Fleming BA, Mulvey MA (2016). Similarly lethal strains of extraintestinal pathogenic Escherichia coli trigger markedly diverse host responses in a zebrafish model of sepsis. mSphere, 1(2), pii: e00062-16.
  7. Lewis AJ, Dhakal BK, Liu T, Mulvey MA (2016). Histone deacetylase 6 regulates bladder architecture and host susceptibility to uropathogenic Escherichia coli. Pathogens, 5(1), Pii: E20.
  8. Russell CW, Mulvey MA (2015). The extraintestinal pathogenic Escherichia coli factor RqlI constrains the genotoxic effects of the RecQ-like helicase RqlH. PLoS Pathog, 11(12), e1005317.
  9. Blango MG, Ott EM, Erman A, Veranic P, Mulvey MA (2014). Forced resurgence and targeting of intracellular uropathogenic Escherichia coli reservoirs. PLoS ONE, 9(3), e93327.
  10. Donovan GT, Norton JP, Bower JM, Mulvey MA (2013). Adenylate cyclase and the cyclic AMP receptor protein modulate stress resistance and virulence capacity of uropathogenic Escherichia coli. Infect Immun, 81(1), 249-58.
  11. Debnath I, Norton JP, Barber AE, Ott EM, Dhakal BK, Kulesus RR, Mulvey MA (2013). The Cpx stress response system potentiates the fitness and virulence of uropathogenic Escherichia coli. Infect Immun, 81(5), 1450-9.
  12. Wiles TJ, Norton JP, Smith SN, Lewis AJ, Mobley HL, Casjens SR, Mulvey MA (2013). A phyletically rare gene promotes the niche-specific fitness of an E. coli pathogen during bacteremia. PLoS Pathog, 9(2), e1003175.
  13. Wiles TJ, Norton JP, Russell CW, Dalley BK, Fischer KF, Mulvey MA (2013). Combining quantitative genetic footprinting and trait enrichment analysis to identify fitness determinants of a bacterial pathogen. PLoS Genet, 9(8), e1003716.
  14. Vigil PD, Wiles TJ, Engstrom MD, Prasov L, Mulvey MA, Mobley HL (2012). The repeat-in-toxin family member TosA mediates adherence of uropathogenic Escherichia coli and survival during bacteremia. Infect Immun, 80(2), 493-505.
  15. Dhakal BK, Mulvey MA (2012). The UPEC pore-forming toxin alpha-hemolysin triggers proteolysis of host proteins to disrupt cell adhesion, inflammatory, and survival pathways. Cell Host Microbe, 11(1), 58-69.
  16. Erman A, Lakota K, Mrak-Poljsak K, Blango MG, Krizan-Hergouth V, Mulvey MA, Sodin-Semrl S, Veranic P (2012). Uropathogenic Escherichia coli induces serum amyloid a in mice following urinary tract and systemic inoculation. PLoS ONE, 7(3), e32933.
  17. Norton JP, Mulvey MA (2012). Toxin-antitoxin systems are important for niche-specific colonization and stress resistance of uropathogenic Escherichia coli. PLoS Pathog, 8(10), e1002954.
  18. Kraemer BF, Campbell RA, Schwertz H, Franks ZG, Vieira de Abreu A, Grundler K, Kile BT, Dhakal BK, Rondina MT, Kahr WH, Mulvey MA, Blaylock RC, Zimmerman GA, Weyrich AS (2012). Bacteria differentially induce degradation of Bcl-xL, a survival protein, by human platelets. Blood, 120(25), 5014-20.
  19. Blango MG, Mulvey MA (2010). Persistence of uropathogenic Escherichia coli in the face of multiple antibiotics. Antimicrob Agents Chemother, 54(5), 1855-63.
  20. Dhakal BK, Mulvey MA (2009). Uropathogenic Escherichia coli invades host cells via an HDAC6-modulated microtubule-dependent pathway. J Biol Chem, 284(1), 446-54.
  21. Bower JM, Gordon-Raagas HB, Mulvey MA (2009). Conditioning of uropathogenic Escherichia coli for enhanced colonization of host. Infect Immun, 77(5), 2104-12.
  22. Kulkarni R, Dhakal BK, Slechta ES, Kurtz Z, Mulvey MA, Thanassi DG (2009). Roles of putative type II secretion and type IV pilus systems in the virulence of uropathogenic Escherichia coli. PLoS ONE, 4(3), e4752.
  23. 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 Pathog, 5(12), e1000697.
  24. Wiles TJ, Dhakal BK, Eto DS, Mulvey MA (2008). Inactivation of host Akt/protein kinase B signaling by bacterial pore-forming toxins. Mol Biol Cell, 19(4), 1427-38.
  25. Kulesus RR, Diaz-Perez K, Slechta ES, Eto DS, Mulvey MA (2008). Impact of the RNA chaperone Hfq on the fitness and virulence potential of uropathogenic Escherichia coli. Infect Immun, 76(7), 3019-26.
  26. Eto DS, Gordon HB, Dhakal BK, Jones TA, 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), 2553-67.
  27. Eto DS, Jones TA, Sundsbak JL, Mulvey MA (2007). Integrin-mediated host cell invasion by type 1-piliated uropathogenic Escherichia coli. PLoS Pathog, 3(7), e100.
  28. Bower JM, Mulvey MA (2006). Polyamine-mediated resistance of uropathogenic Escherichia coli to nitrosative stress. J Bacteriol, 188(3), 928-33.
  29. Eto DS, Sundsbak JL, Mulvey MA (2006). Actin-gated intracellular growth and resurgence of uropathogenic Escherichia coli. Cell Microbiol, 8(4), 704-17.
  30. Schilling JD, Martin SM, Hunstad DA, Patel KP, Mulvey MA, Justice SS, Lorenz RG, Hultgren SJ (2003). CD14- and Toll-like receptor-dependent activation of bladder epithelial cells by lipopolysaccharide and type 1 piliated Escherichia coli. Infect Immun, 71(3), 1470-80.
  31. Mysorekar IU, Mulvey MA, Hultgren SJ, Gordon JI (2002). Molecular regulation of urothelial renewal and host defenses during infection with uropathogenic Escherichia coli. J Biol Chem, 277(9), 7412-9.
  32. Schilling JD, Mulvey MA, Vincent CD, Lorenz RG, Hultgren SJ (2001). Bacterial invasion augments epithelial cytokine responses to Escherichia coli through a lipopolysaccharide-dependent mechanism. J Immunol, 166(2), 1148-55.
  33. Mulvey MA, Schilling JD, Hultgren SJ (2001). Establishment of a persistent Escherichia coli reservoir during the acute phase of a bladder infection. Infect Immun, 69(7), 4572-9.
  34. Martinez JJ, Mulvey MA, Schilling JD, Pinkner JS, Hultgren SJ (2000). Type 1 pilus-mediated bacterial invasion of bladder epithelial cells. EMBO J, 19(12), 2803-12.
  35. Mulvey MA, Lopez-Boado YS, Wilson CL, Roth R, Parks WC, Heuser J, Hultgren SJ (1998). Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. Science, 282(5393), 1494-7.
  36. Knight S, Mulvey M, Pinkner J (1997). Crystallization and preliminary X-ray diffraction studies of the FimC-FimH chaperone-adhesin complex from Escherichia coli. Acta Crystallogr, D53, 207-210.
  37. Carleton M, Lee H, Mulvey M, Brown DT (1997). Role of glycoprotein PE2 in formation and maturation of the Sindbis virus spike. J Virol, 71(2), 1558-66.
  38. Mulvey M, Brown DT (1996). Assembly of the Sindbis virus spike protein complex. Virology, 219(1), 125-32.
  39. Mulvey M, Brown DT (1995). Involvement of the molecular chaperone BiP in maturation of Sindbis virus envelope glycoproteins. J Virol, 69(3), 1621-7.
  40. Mulvey M, Brown DT (1994). Formation and rearrangement of disulfide bonds during maturation of the Sindbis virus E1 glycoprotein. J Virol, 68(2), 805-12.

Review

  1. Lewis AJ, Richards AC, Mulvey MA (2016). Invasion of Host Cells and Tissues by Uropathogenic Bacteria. [Review]. Microbiology Spectrum, 4(6), UTI-0026-2016.
  2. Barber AE, Norton JP, Wiles TJ, Mulvey MA (2016). Strengths and limitations of model systems for the study of urinary tract infections and related pathologies. [Review]. Microbiology and Molecular Biology Reviews, 80(2), 351-367.
  3. Wiles TJ, Mulvey MA (2013). The RTX pore-forming toxin alpha-hemolysin of uropathogenic Escherichia coli: progress and perspectives. [Review]. Future Microbiology, 8(1), 73-84.
  4. Barber AE, Norton JP, Spivak AM, Mulvey MA (2013). Urinary tract infections: current and emerging management strategies. [Review]. Clinical Infectious Diseases, 57(5), 719-24.
  5. Blango MG, Mulvey MA (2009). Bacterial landlines: contact-dependent signaling in bacterial populations. [Review]. Current Opinion in Microbiology, 12(2), 177-81.
  6. Wiles TJ, Kulesus RR, Mulvey MA (2008). Origins and virulence mechanisms of uropathogenic Escherichia coli. [Review]. Exp Mol Pathol, 85(1), 11-9.
  7. Dhakal BK, Kulesus RR, Mulvey MA (2008). Mechanisms and consequences of bladder cell invasion by uropathogenic Escherichia coli. [Review]. Eur J Clin Invest, 38 Suppl 2, 2-11.
  8. Eto DS and Mulvey MA (2007). Flushing bacteria out from the bladder. [Review]. Nature Medicine, 13(5), 531-532.
  9. Slechta ES, Mulvey MA (2006). Contact-dependent inhibition: bacterial brakes and secret handshakes. [Review]. Trends Microbiol, 14(2), 58-60.
  10. Bower JM, Eto DS, Mulvey MA (2005). Covert operations of uropathogenic Escherichia coli within the urinary tract. [Review]. Traffic, 6(1), 18-31.
  11. Mulvey MA (2002). Adhesion and entry of uropathogenic Escherichia coli. [Review]. Cell Microbiol, 4(5), 257-71.
  12. Schilling JD, Mulvey MA, Hultgren SJ (2001). Structure and function of Escherichia coli type 1 pili: new insight into the pathogenesis of urinary tract infections. [Review]. J Infect Dis, 183 Suppl 1, S36-40.
  13. Schilling JD, Mulvey MA, Hultgren SJ (2001). Dynamic interactions between host and pathogen during acute urinary tract infections. [Review]. Urology, 57(6 Suppl 1), 56-61.
  14. Sauer FG, Mulvey MA, Schilling JD, Martinez JJ, Hultgren SJ (2000). Bacterial pili: molecular mechanisms of pathogenesis. [Review]. Curr Opin Microbiol, 3(1), 65-72.
  15. Mulvey MA, Schilling JD, Martinez JJ, Hultgren SJ (2000). Bad bugs and beleaguered bladders: interplay between uropathogenic Escherichia coli and innate host defenses. [Review]. Proc Natl Acad Sci U S A, 97(16), 8829-35.
  16. Mulvey MA, Hultgren SJ (2000). Cell biology. Bacterial spelunkers. [Review]. Science, 289(5480), 732-3.

Edited Book

  1. Mulvey MA, Stapleton AE, Klumpp DJ (Eds.) (2017). Urinary Tract Infections: Molecular Pathogenesis and Clinical Management. (2nd). Washington, D.C.: ASM Press.

Book Chapter

  1. Lewis AJ, Richards AC, Mulvey MA (2017). Invasion of host cells and tissues by uropathogenic bacteria. In Mulvey MA, Stapleton AE, Klumpp DJ (Eds.), Urinary Tract Infections: Molecular Pathogenesis and Clinical Management (2nd, pp. 359–382). Washington, D.C.: ASM Press.
  2. Fleming BA, Mulvey MA (2016). Toxin-antitoxin systems as regulators of bacterial fitness and virulence. In F.J. de Bruijn (Ed.), Stress and Environmental Regulation of Gene Expression and Adaptation in Bacteria. Hoboken, NJ: John Wiley & Sons, Inc.
  3. Russell CW, Mulvey MA (2014). Type 1 and P Pili of Uropathogenic Escherichia coli. In M Borrochi and JL Telford (Eds.), Bacterial Pili: Structure, Synthesis and Role in Disease (pp. 49 - 70). Wallingford, UK: CAB International.
  4. Lewis AJ, Ott EM, Wiles TJ, Mulvey MA (2014). Invasion of Host Cells by Pathogenic E. coli. In S Morabito (Ed.), Pathogenic Escherichia coli: Molecular and Cellular Microbiology (pp. 231 - 254). Norwich, United Kingdom: Horizon Scientific Press.
  5. Dhakal BK, Bower JM, Mulvey MA (2009). Pili, Fimbriae. In M. Schaechter (Ed.), The Desk Encyclopedia of Microbiology (2nd, pp. 861-880). Oxford: Elsevier.
  6. Dhakal BK, Bower JM, Mulvey MA (2009). Pili, Fimbriae. In M. Schaechter (Ed.), Encyclopedia of Microbiology (3rd, pp. 470-489). Oxford: Elsevier.
  7. Chapman MR, Mulvey MA, Hultgren SJ (2001). Fimbriae and Pili. In Sussman M (Ed.), Molecular Medical Microbiology (pp. 177-198). London: Academic Press.
  8. Mulvey MA, Dodson KW, Soto GE, Hultgren SJ (2000). Fimbriae, Pili. In Lederberg J, et al (Eds.), Encyclopedia of Microbiology, 2nd Edition (pp. 361-379). New York: Academic Press.
  9. Mulvey MA, Hultgren SJ (2000). Adhesion, Bacterial. In Lederberg J, et al (Eds.), Encyclopedia of Microbiology, 2nd Edition (pp. 42-52). New York: Academic Press.
  10. Mulvey MA, Hultgren SJ, Langermann S (2000). Development of an Adhesin Vaccine to Prevent Urinary Tract Infection. In Lohner K (Ed.), Development of Novel Antimicrobial Agents: Emerging Strategies (pp. 123-138). Norfolk: Horizon Scientific Press.

Commentary

  1. Mulvey MA and Tantin D (09/05/2014). Opinion: An Ecclesiastical Approach to Peer Review.
    http://www.the-scientist.com//?articles.view/articleNo/40901/title/Opinion--An-Ecclesiastical-Approach-to-Peer-Review/. The Scientist.

Book Review

  1. Bower JM, Mulvey MA (2002). Gripping Tales of Bacterial Pathogenesis. [Review of the book Bacterial Adhesion to Host Tissues: Mechanisms and Consequences]. Cell, 111, 447-448.

Letter

  1. Barber AE, Mulvey MA (2014). Reply to Kaye and Sobel [Letter to the editor]. Clin Infect Dis, 58(3), 444-5.