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Professor, Microbiology; Molecular Virology, Immunology and Medical Genetics
Vice Director, Center for Microbial Interface Biology (CMIB)
Member, CMIB
Member, OSBP
Member, IBGP
Salmonella/Francisella
pathogenesis and host cell interactions
Dr. Gunn's laboratory is primarily interested in the molecular mechanisms used by Salmonella spp. to survive harsh conditions it encounters within the human host. Salmonellae encounter numerous anatomic sites during infection, including the inhospitable environment of the macrophage phagosome, where they are able to survive and replicate. Present within host phagocytes (and at mucosal surfaces) are a potent group of cytotoxic agents, antimicrobial peptides (AP). The PmrA-PmrB two-component regulatory system is activated when Salmonella are within host macrophages, and is necessary for resistance to AP, which involves modifications of the LPS that decrease peptide binding. He is focused on studies of the PmrA-PmrB regulon, including the identification and characterization of PmrA-PmrB regulated genes necessary for AP resistance and LPS modification, and the determination of the role of PmrA-PmrB mediated LPS modifications in Salmonella virulence.
Bile salts are detergents made by the liver that are stored in the gallbladder and released into the intestine to aid digestion. Salmonella spp. come in contact with bile salts in the intestine, and in the chronic carrier state, within the gallbladder. Salmonella is able to resist the action of bile and respond to escalating bile concentrations by increasing mechanisms of resistance. He is currently trying to understand: (1) how Salmonella is able to sense bile, (2) what mechanisms of bile resistance exist in Salmonella, and (3) how biofilm formation on gallstones may aid in development of the carrier state.
Finally, Dr. Gunn's laboratory is interested in pathogenesis and intramacrophage survival of the Category A biodefense agent, Francisella tularensis . This work involves the identification of genes required for survival against both oxygen dependent and oxygen independent killing within phagocytes, as well as genes induced in this intracellular environment. The development of live-attenuated Salmonella-based vaccines against tularemia (as well as other food-borne and biodefense-related diseases) are a goal of this work. |
Mohapatra, N.P., S. Soni, T.J. Reilly, J. Liu, K.E. Klose and J.S. Gunn. 2008. The combined deletion of four Francisella acid phosphatases attenuates virulence and macrophage vacuolar escape. Infect. Immun. 76:3690-3699.
Crawford, R.W., D.L. Gibson, W.W. Kay, and J.S. Gunn. 2008. Identification of a bile-induced exopolysaccharide required for Salmonella biofilm formation on gallstone surfaces. Infect Immun. 76:5341-9.
Clay, C.D., S. Soni, J.S. Gunn and L.S. Schlesinger. 2008. Evasion of complement-mediated lysis and complement C3 deposition are regulated by Francisella tularensis LPS O-antigen. J. Immunol. 181:5568-78.
Mohaptara, N., A. Balagopal, S. Soni, L.S. Schlesinger, and J.S. Gunn. 2007. AcpA, an Acid Phosphatase involved in Francisella tularensis Virulence. Infect. Immun.75:390-6.
Mohapatra, N.P., S. Soni, B.L. Bell, R. Warren, R.K. Ernst, A. Muszynski, R. Carlson, and J.S. Gunn. 2007. Identification of an orphan response regulator required for Francisella virulence and transcription of pathogenicity island genes. Infect. Immun. 75:3305-14.
Gavrilin, M.A, I. Bouakl, N. Knatz, M. Duncan, M.W. Hall, J.S. Gunn and M.D. Wewers. 2006. Internalization and phagosome escape required for live Francisella to induce human monocyte IL-1b processing and release. PNAS 103:141-146.
Merighi, M., C.D. Ellermeier, J.M. Slauch and J.S. Gunn. 2005. Resolvase-IVET Analysis of the Salmonella enterica sv. Typhimurium PhoP and PmrA regulons in BALB/c mice. J. Bacteriol.187:7407-7416.
Tamayo, R., B. Choudhury, A. Septer, M. Merighi, R. Carlson and J.S. Gunn. 2005. Identification of cptA, a PmrA-Regulated Locus Required for Phosphoethanolamine Modification of the Salmonella enterica serovar Typhimurium Lipopolysaccharide Core. J. Bacteriol. 187:3391-3399.
Tamayo,
R., A.C. Portillo, and J.S. Gunn. 2004. “Mechanisms of Bacterial
Resistance to Antimicrobial Peptides”, In
Mammalian Host Defence Peptides, pp. 323-348,
D.A.Devine, R.E.W. Hancock, eds., Cambridge
Univ. Press.
Vinogradov,
E., W.J. Conlan, J.S. Gunn, and M.B. Perry. 2004. Characterization
of the lipopolysaccharide O-antigen of Francisella
novicida (U112). Carbohydr. Res. 339:649-654.
Prouty,
A,M., I.E. Brodsky, S. Falkow, and J.S.
Gunn. 2004. Bile salt-mediated
induction of antimicrobial and bile resistance
in Salmonella typhimurium. Microbiology.
150:775-83.
Prouty,
A.M. and J.S. Gunn.
2002. Biofilm Formation and Interaction
with the Surfaces of Gallstones by
Salmonella spp.. Infect. Immun. 70 :2640-2649.
Tamayo,
R., S.S. Ryan, A.J. McCoy, and J.S.
Gunn. 2002. Identification and
genetic characterization of PmrA-regulated
genes and genes involved in polymyxin B
resistance in Salmonella enterica
Serovar Typhimurium. Infect. Immun. 70:6770-6678.
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