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Paul Dunman

Title	Associate Professor
Institution	School of Medicine and Dentistry
Department	Microbiology and Immunology
Address	University of Rochester Medical Center School of Medicine and Dentistry 601 Elmwood Ave, Box 672 Rochester NY 14642

Awards And Honors

2003			Young Investigator of the Year \| International Conference on Antimicrobial Agents and Chemotherap
2009			Joseph P. Gilmore Outstanding Investigator Award \| University of Nebraska Medical Center
2009			Most Promising New Invention Notification \| University of Nebraska Medical Center
2010			Distinguished Investigator \| University of Nebraska Medical Center

Overview

Dunman Laboratory Research Overview:

Staphylococcus aureus is a Gram-positive bacterial pathogen that is reported to cause more U.S. deaths annually than HIV. Acinetobacter baumannii is a Gram-negative pathogen that is emerging as a predominant cause of infections within military personnel injured during Operation Iraqi Freedom and has recently caused deadly outbreaks in the U.S., South America, and Europe. In addition to causing high incidences of morbidity and mortality, both organisms have also developed resistance to all currently available antibiotics, further amplifying public health concern and accentuating the need for new antibiotics for the treatment of S. aureus and A. baumannii infections.

Our laboratory uses S. aureus and A. baumannii as model organisms to study bacterial pathogenesis and develop novel strategies for the therapeutic intervention of bacterial infections. That work has revealed that most bacterial virulence factors are post-transcriptionally regulated in a manner that involves the modulation of their mRNA turnover. Current laboratory projects are geared toward characterizing the molecular components that govern 'native' and temporal changes in mRNA degradation. These factors can be broadly categorized as either: small non-coding RNAs, ribonucleases, or RNA binding proteins. We have purified and exploited several of these factors as targets for antimicrobial drug discovery.

Relevant Recent Publications:

1. Small molecule inhibitors of Staphylococcus aureus RnpA alter cellular mRNA turnover, exhibit antimicrobial activity, and attenuate pathogenesis. Olson PD, Kuechenmeister LJ, Anderson KL, Daily S, Beenken KE, Roux CM, Reniere ML, Lewis TL, Weiss WJ, Pulse M, Nguyen P, Simecka JW, Morrison JM, Sayood K, Asojo OA, Smeltzer MS, Skaar EP, and Dunman PM. PLoS Pathogens 2011 (in press).

2. Characterizing the effects of inorganic acid and alkaline shock on the Staphylococcus aureus transcriptome and messenger RNA turnover. Anderson KL, Roux CM, Olson MW, Luong TT, Lee CY, Olson R, and Dunman PM. FEMS Immunol Med Microbiol 2010 60(3):208.

3. Staphylococcus aureus nonribosomal peptide secondary metabolites regulate virulence. Wyatt MA, Wang W, Roux CM, Beasley FC, Heinrichs DE, Dunman PM and Magarvey NA. Science 2010 329(5989):294.

4. Inactivation of phospholipase D diminishes Acinetobacter baumannii pathogenesis. Jacobs AC, Hood I, Boyd KL, Olson PD, Morrison JM, Carson S, Sayood K, Iwen PC, Skaar EP, and Dunman PM. Infect Immun 2010 78(5):1952.

Selected Publications

Hood MI, Becker KW, Roux CM, Dunman PM, Skaar EP. Genetic Determinants of Intrinsic Colistin Tolerance in Acinetobacter baumannii. Infect Immun. 2013 Feb; 81(2):542-51.

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Brinkman CL, Bumgarner R, Kittichotirat W, Dunman PM, Kuechenmeister LJ, Weaver KE. Characterization of the Effects of an rpoC Mutation That Confers Resistance to the Fst Peptide Toxin-Antitoxin System Toxin. J Bacteriol. 2013 Jan; 195(1):156-66.

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Annadurai S, Martinez R, Canney DJ, Eidem T, Dunman PM, Abou-Gharbia M. Design and synthesis of 2-aminothiazole based antimicrobials targeting MRSA. Bioorg Med Chem Lett. 2012 Dec 15; 22(24):7719-25.

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Jacobs AC, Didone L, Jobson J, Sofia MK, Krysan D, Dunman PM. Adenylate kinase release as a high-throughput-screening-compatible reporter of bacterial lysis for identification of antibacterial agents. Antimicrob Agents Chemother. 2013 Jan; 57(1):26-36.

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Caswell CC, Gaines JM, Ciborowski P, Smith D, Borchers CH, Roux CM, Sayood K, Dunman PM, Roop Ii RM. Identification of two small regulatory RNAs linked to virulence in Brucella abortus 2308. Mol Microbiol. 2012 Jul; 85(2):345-60.

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Anbalagan S, Dmitriev A, McShan WM, Dunman PM, Chaussee MS. Growth Phase-Dependent Modulation of Rgg Binding Specificity in Streptococcus pyogenes. J Bacteriol. 2012 Aug; 194(15):3961-71.

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Morrison JM, Miller EW, Benson MA, Alonzo F, Yoong P, Torres VJ, Hinrichs SH, Dunman PM. Characterization of SSR42, a Novel Virulence Factor Regulatory RNA That Contributes to the Pathogenesis of a Staphylococcus aureus USA300 Representative. J Bacteriol. 2012 Jun; 194(11):2924-38.

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Morrison JM, Anderson KL, Beenken KE, Smeltzer MS, Dunman PM. The Staphylococcal Accessory Regulator, SarA, is an RNA-Binding Protein that Modulates the mRNA Turnover Properties of Late-Exponential and Stationary Phase Staphylococcus aureus Cells. Front Cell Infect Microbiol. 2012; 2:26.

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Eidem TM, Roux CM, Dunman PM. RNA decay: a novel therapeutic target in bacteria. Wiley Interdiscip Rev RNA. 2012 May; 3(3):443-54.

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Gardete S, Kim C, Hartmann BM, Mwangi M, Roux CM, Dunman PM, Chambers HF, Tomasz A. Genetic Pathway in Acquisition and Loss of Vancomycin Resistance in a Methicillin Resistant Staphylococcus aureus (MRSA) Strain of Clonal Type USA300. PLoS Pathog. 2012 Feb; 8(2):e1002505.

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Jacobs AC, Sayood K, Olmsted SB, Blanchard CE, Hinrichs S, Russell D, Dunman PM. Characterization of the Acinetobacter baumannii growth phase-dependent and serum responsive transcriptomes. FEMS Immunol Med Microbiol. 2012 Apr; 64(3):403-12.

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Morrison JM, Dunman PM. The modulation of Staphylococcus aureus mRNA turnover. Future Microbiol. 2011 Oct; 6(10):1141-50.

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Truong-Bolduc QC, Dunman PM, Eidem T, Hooper DC. Transcriptional profiling analysis of the global regulator NorG, a GntR-like protein of Staphylococcus aureus. J Bacteriol. 2011 Nov; 193(22):6207-14.

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Lei MG, Cue D, Roux CM, Dunman PM, Lee CY. Rsp inhibits attachment and biofilm formation by repressing fnbA in Staphylococcus aureus MW2. J Bacteriol. 2011 Oct; 193(19):5231-41.

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Anbalagan S, McShan WM, Dunman PM, Chaussee MS. Identification of Rgg binding sites in the Streptococcus pyogenes chromosome. J Bacteriol. 2011 Sep; 193(18):4933-42.

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Roux CM, DeMuth JP, Dunman PM. Characterization of components of the Staphylococcus aureus mRNA degradosome holoenzyme-like complex. J Bacteriol. 2011 Oct; 193(19):5520-6.

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Olson PD, Kuechenmeister LJ, Anderson KL, Daily S, Beenken KE, Roux CM, Reniere ML, Lewis TL, Weiss WJ, Pulse M, Nguyen P, Simecka JW, Morrison JM, Sayood K, Asojo OA, Smeltzer MS, Skaar EP, Dunman PM. Small molecule inhibitors of Staphylococcus aureus RnpA alter cellular mRNA turnover, exhibit antimicrobial activity, and attenuate pathogenesis. PLoS Pathog. 2011; 7(2):e1001287.

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Luong TT, Sau K, Roux C, Sau S, Dunman PM, Lee CY. Staphylococcus aureus ClpC divergently regulates capsule via sae and codY in strain newman but activates capsule via codY in strain UAMS-1 and in strain Newman with repaired saeS. J Bacteriol. 2011 Feb; 193(3):686-94.

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Anderson KL, Roux CM, Olson MW, Luong TT, Lee CY, Olson R, Dunman PM. Characterizing the effects of inorganic acid and alkaline shock on the Staphylococcus aureus transcriptome and messenger RNA turnover. FEMS Immunol Med Microbiol. 2010 Dec; 60(3):208-50.

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Wyatt MA, Wang W, Roux CM, Beasley FC, Heinrichs DE, Dunman PM, Magarvey NA. Staphylococcus aureus nonribosomal peptide secondary metabolites regulate virulence. Science. 2010 Jul 16; 329(5989):294-6.

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Lan L, Cheng A, Dunman PM, Missiakas D, He C. Golden pigment production and virulence gene expression are affected by metabolisms in Staphylococcus aureus. J Bacteriol. 2010 Jun; 192(12):3068-77.

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Majerczyk CD, Dunman PM, Luong TT, Lee CY, Sadykov MR, Somerville GA, Bodi K, Sonenshein AL. Direct targets of CodY in Staphylococcus aureus. J Bacteriol. 2010 Jun; 192(11):2861-77.

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Jacobs AC, Hood I, Boyd KL, Olson PD, Morrison JM, Carson S, Sayood K, Iwen PC, Skaar EP, Dunman PM. Inactivation of phospholipase D diminishes Acinetobacter baumannii pathogenesis. Infect Immun. 2010 May; 78(5):1952-62.

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Torres VJ, Attia AS, Mason WJ, Hood MI, Corbin BD, Beasley FC, Anderson KL, Stauff DL, McDonald WH, Zimmerman LJ, Friedman DB, Heinrichs DE, Dunman PM, Skaar EP. Staphylococcus aureus fur regulates the expression of virulence factors that contribute to the pathogenesis of pneumonia. Infect Immun. 2010 Apr; 78(4):1618-28.

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Hood MI, Jacobs AC, Sayood K, Dunman PM, Skaar EP. Acinetobacter baumannii increases tolerance to antibiotics in response to monovalent cations. Antimicrob Agents Chemother. 2010 Mar; 54(3):1029-41.

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Lu SH, Ni Tun MH, Mei ZJ, Chia GH, Lim X, Sow CH. Improved hydrophobicity of carbon nanotube arrays with micropatterning. Langmuir. 2009 Nov 3; 25(21):12806-11.

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Kuhn G, Koessler T, Melles DC, Francois P, Huyghe A, Dunman P, Vos MC, Zanetti G, Schrenzel J, van Belkum A, Blanc DS. Comparative genomics of epidemic versus sporadic Staphylococcus aureus strains does not reveal molecular markers for epidemicity. Infect Genet Evol. 2010 Jan; 10(1):89-96.

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Cue D, Lei MG, Luong TT, Kuechenmeister L, Dunman PM, O'Donnell S, Rowe S, O'Gara JP, Lee CY. Rbf promotes biofilm formation by Staphylococcus aureus via repression of icaR, a negative regulator of icaADBC. J Bacteriol. 2009 Oct; 191(20):6363-73.

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Goering RV, Larsen AR, Skov R, Tenover FC, Anderson KL, Dunman PM. Comparative genomic analysis of European and Middle Eastern community-associated methicillin-resistant Staphylococcus aureus (CC80:ST80-IV) isolates by high-density microarray. Clin Microbiol Infect. 2009 Aug; 15(8):748-55.

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Sharma-Kuinkel BK, Mann EE, Ahn JS, Kuechenmeister LJ, Dunman PM, Bayles KW. The Staphylococcus aureus LytSR two-component regulatory system affects biofilm formation. J Bacteriol. 2009 Aug; 191(15):4767-75.

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Yang SJ, Xiong YQ, Dunman PM, Schrenzel J, François P, Peschel A, Bayer AS. Regulation of mprF in daptomycin-nonsusceptible Staphylococcus aureus strains. Antimicrob Agents Chemother. 2009 Jun; 53(6):2636-7.

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Anderson KL, Dunman PM. Messenger RNA Turnover Processes in Escherichia coli, Bacillus subtilis, and Emerging Studies in Staphylococcus aureus. Int J Microbiol. 2009; 2009:525491.

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Chen PR, Nishida S, Poor CB, Cheng A, Bae T, Kuechenmeister L, Dunman PM, Missiakas D, He C. A new oxidative sensing and regulation pathway mediated by the MgrA homologue SarZ in Staphylococcus aureus. Mol Microbiol. 2009 Jan; 71(1):198-211.

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Kuechenmeister LJ, Anderson KL, Morrison JM, Dunman PM. The use of molecular beacons to directly measure bacterial mRNA abundances and transcript degradation. J Microbiol Methods. 2009 Feb; 76(2):146-51.

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Stauff DL, Bagaley D, Torres VJ, Joyce R, Anderson KL, Kuechenmeister L, Dunman PM, Skaar EP. Staphylococcus aureus HrtA is an ATPase required for protection against heme toxicity and prevention of a transcriptional heme stress response. J Bacteriol. 2008 May; 190(10):3588-96.

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Corbin BD, Seeley EH, Raab A, Feldmann J, Miller MR, Torres VJ, Anderson KL, Dattilo BM, Dunman PM, Gerads R, Caprioli RM, Nacken W, Chazin WJ, Skaar EP. Metal chelation and inhibition of bacterial growth in tissue abscesses. Science. 2008 Feb 15; 319(5865):962-5.

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Alksne LE, Dunman PM. Target-based antimicrobial drug discovery. Methods Mol Biol. 2008; 431:271-83.

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Handke LD, Rogers KL, Olson ME, Somerville GA, Jerrells TJ, Rupp ME, Dunman PM, Fey PD. Staphylococcus epidermidis saeR is an effector of anaerobic growth and a mediator of acute inflammation. Infect Immun. 2008 Jan; 76(1):141-52.

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Torres VJ, Stauff DL, Pishchany G, Bezbradica JS, Gordy LE, Iturregui J, Anderson KL, Dunman PM, Joyce S, Skaar EP. A Staphylococcus aureus regulatory system that responds to host heme and modulates virulence. Cell Host Microbe. 2007 Apr 19; 1(2):109-19.

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Anderson KL, Roberts C, Disz T, Vonstein V, Hwang K, Overbeek R, Olson PD, Projan SJ, Dunman PM. Characterization of the Staphylococcus aureus heat shock, cold shock, stringent, and SOS responses and their effects on log-phase mRNA turnover. J Bacteriol. 2006 Oct; 188(19):6739-56.

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Cassat J, Dunman PM, Murphy E, Projan SJ, Beenken KE, Palm KJ, Yang SJ, Rice KC, Bayles KW, Smeltzer MS. Transcriptional profiling of a Staphylococcus aureus clinical isolate and its isogenic agr and sarA mutants reveals global differences in comparison to the laboratory strain RN6390. Microbiology. 2006 Oct; 152(Pt 10):3075-90.

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Projan SJ, Nesin M, Dunman PM. Staphylococcal vaccines and immunotherapy: to dream the impossible dream? Curr Opin Pharmacol. 2006 Oct; 6(5):473-9.

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Richardson AR, Dunman PM, Fang FC. The nitrosative stress response of Staphylococcus aureus is required for resistance to innate immunity. Mol Microbiol. 2006 Aug; 61(4):927-39.

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Roberts C, Anderson KL, Murphy E, Projan SJ, Mounts W, Hurlburt B, Smeltzer M, Overbeek R, Disz T, Dunman PM. Characterizing the effect of the Staphylococcus aureus virulence factor regulator, SarA, on log-phase mRNA half-lives. J Bacteriol. 2006 Apr; 188(7):2593-603.

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Yang SJ, Dunman PM, Projan SJ, Bayles KW. Characterization of the Staphylococcus aureus CidR regulon: elucidation of a novel role for acetoin metabolism in cell death and lysis. Mol Microbiol. 2006 Apr; 60(2):458-68.

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Luong TT, Dunman PM, Murphy E, Projan SJ, Lee CY. Transcription Profiling of the mgrA Regulon in Staphylococcus aureus. J Bacteriol. 2006 Mar; 188(5):1899-910.

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McAleese F, Wu SW, Sieradzki K, Dunman P, Murphy E, Projan S, Tomasz A. Overexpression of genes of the cell wall stimulon in clinical isolates of Staphylococcus aureus exhibiting vancomycin-intermediate- S. aureus-type resistance to vancomycin. J Bacteriol. 2006 Feb; 188(3):1120-33.

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Tenover FC, McDougal LK, Goering RV, Killgore G, Projan SJ, Patel JB, Dunman PM. Characterization of a strain of community-associated methicillin-resistant Staphylococcus aureus widely disseminated in the United States. J Clin Microbiol. 2006 Jan; 44(1):108-18.

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McAleese F, Murphy E, Babinchak T, Singh G, Said-Salim B, Kreiswirth B, Dunman P, O'Connell J, Projan SJ, Bradford PA. Use of ribotyping to retrospectively identify methicillin-resistant Staphylococcus aureus isolates from phase 3 clinical trials for tigecycline that are genotypically related to community-associated isolates. Antimicrob Agents Chemother. 2005 Nov; 49(11):4521-9.

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Tarkin IS, Dunman PM, Garvin KL. Improving the treatment of musculoskeletal infections with molecular diagnostics. Clin Orthop Relat Res. 2005 Aug; (437):83-8.

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McAleese F, Petersen P, Ruzin A, Dunman PM, Murphy E, Projan SJ, Bradford PA. A novel MATE family efflux pump contributes to the reduced susceptibility of laboratory-derived Staphylococcus aureus mutants to tigecycline. Antimicrob Agents Chemother. 2005 May; 49(5):1865-71.

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Truong-Bolduc QC, Dunman PM, Strahilevitz J, Projan SJ, Hooper DC. MgrA is a multiple regulator of two new efflux pumps in Staphylococcus aureus. J Bacteriol. 2005 Apr; 187(7):2395-405.

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Entenza JM, Moreillon P, Senn MM, Kormanec J, Dunman PM, Berger-Bächi B, Projan S, Bischoff M. Role of sigmaB in the expression of Staphylococcus aureus cell wall adhesins ClfA and FnbA and contribution to infectivity in a rat model of experimental endocarditis. Infect Immun. 2005 Feb; 73(2):990-8.

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Cassat JE, Dunman PM, McAleese F, Murphy E, Projan SJ, Smeltzer MS. Comparative genomics of Staphylococcus aureus musculoskeletal isolates. J Bacteriol. 2005 Jan; 187(2):576-92.

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Weinrick B, Dunman PM, McAleese F, Murphy E, Projan SJ, Fang Y, Novick RP. Effect of mild acid on gene expression in Staphylococcus aureus. J Bacteriol. 2004 Dec; 186(24):8407-23.

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Dunman PM, Mounts W, McAleese F, Immermann F, Macapagal D, Marsilio E, McDougal L, Tenover FC, Bradford PA, Petersen PJ, Projan SJ, Murphy E. Uses of Staphylococcus aureus GeneChips in genotyping and genetic composition analysis. J Clin Microbiol. 2004 Sep; 42(9):4275-83.

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Beenken KE, Dunman PM, McAleese F, Macapagal D, Murphy E, Projan SJ, Blevins JS, Smeltzer MS. Global gene expression in Staphylococcus aureus biofilms. J Bacteriol. 2004 Jul; 186(14):4665-84.

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Bischoff M, Dunman P, Kormanec J, Macapagal D, Murphy E, Mounts W, Berger-Bächi B, Projan S. Microarray-based analysis of the Staphylococcus aureus sigmaB regulon. J Bacteriol. 2004 Jul; 186(13):4085-99.

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Utaida S, Dunman PM, Macapagal D, Murphy E, Projan SJ, Singh VK, Jayaswal RK, Wilkinson BJ. Genome-wide transcriptional profiling of the response of Staphylococcus aureus to cell-wall-active antibiotics reveals a cell-wall-stress stimulon. Microbiology. 2003 Oct; 149(Pt 10):2719-32.

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Dunman PM, Nesin M. Passive immunization as prophylaxis: when and where will this work? Curr Opin Pharmacol. 2003 Oct; 3(5):486-96.

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Saïd-Salim B, Dunman PM, McAleese FM, Macapagal D, Murphy E, McNamara PJ, Arvidson S, Foster TJ, Projan SJ, Kreiswirth BN. Global regulation of Staphylococcus aureus genes by Rot. J Bacteriol. 2003 Jan; 185(2):610-9.

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Haney SA, Alksne LE, Dunman PM, Murphy E, Projan SJ. Genomics in anti-infective drug discovery--getting to endgame. Curr Pharm Des. 2002; 8(13):1099-118.

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Dunman PM, Murphy E, Haney S, Palacios D, Tucker-Kellogg G, Wu S, Brown EL, Zagursky RJ, Shlaes D, Projan SJ. Transcription profiling-based identification of Staphylococcus aureus genes regulated by the agr and/or sarA loci. J Bacteriol. 2001 Dec; 183(24):7341-53.

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Livermore DM, Warner M, Hall LM, Enne VI, Projan SJ, Dunman PM, Wooster SL, Harrison G. Antibiotic resistance in bacteria from magpies (Pica pica) and rabbits (Oryctolagus cuniculus) from west Wales. Environ Microbiol. 2001 Oct; 3(10):658-61.

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Dunman P. Patient advocacy. Winning ways. Health Serv J. 2001 May 10; 111(5754):20-3.

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Dunman P. NHS Plan. Stand by me. Interview by Charlotte Alderman. Nurs Stand. 2000 Aug 16-22; 14(48):13.

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Dunman PM, Ren L, Rahman MS, Palejwala VA, Murphy HS, Volkert MR, Humayun MZ. Escherichia coli cells defective for the recN gene display constitutive elevation of mutagenesis at 3,N(4)-ethenocytosine via an SOS-induced mechanism. Mol Microbiol. 2000 Aug; 37(3):680-6.

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Wang G, Dunman PM, Humayun MZ. Replication of M13 single-stranded DNA bearing a site-specific ethenocytosine lesion by Escherichia coil cell extracts. Cell Res. 1997 Jun; 7(1):1-12.

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Murphy HS, Palejwala VA, Rahman MS, Dunman PM, Wang G, Humayun MZ. Role of mismatch repair in the Escherichia coli UVM response. J Bacteriol. 1996 Dec; 178(23):6651-7.

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Rahman MS, Dunman PM, Wang G, Murphy HS, Humayun MZ. Effect of UVM induction on mutation fixation at non-pairing and mispairing DNA lesions. Mol Microbiol. 1996 Nov; 22(4):747-55.

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Wang G, Palejwala VA, Dunman PM, Aviv DH, Murphy HS, Rahman MS, Humayun MZ. Alkylating agents induce UVM, a recA-independent inducible mutagenic phenomenon in Escherichia coli. Genetics. 1995 Nov; 141(3):813-23.

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Palejwala VA, Pandya GA, Bhanot OS, Solomon JJ, Murphy HS, Dunman PM, Humayun MZ. UVM, an ultraviolet-inducible RecA-independent mutagenic phenomenon in Escherichia coli. J Biol Chem. 1994 Nov 4; 269(44):27433-40.

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