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gunn.43@osu.edu
Associate
Professor
B.S., Bowling Green State University,
1988
Ph.D., University of Maryland, 1993
Post-doc, Mass. General Hospital/Harvard
Medical School, University of Washington
1993-1997
Center
for Microbial Interface Biology (CMIB)
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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.
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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.
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.
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