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Infection and Immunity, April 1999, p. 1614-1622, Vol. 67, No. 4
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
PhoP-PhoQ-Regulated Loci Are Required for Enhanced
Bile Resistance in Salmonella spp.
Jennifer C.
van Velkinburgh, and
John S.
Gunn*
Department of Microbiology, University of
Texas Health Science Center at San Antonio, San Antonio, Texas
78284-7758
Received 4 November 1998/Returned for modification 17 December
1998/Accepted 31 December 1998
As enteric pathogens, Salmonella spp. are resistant to
the actions of bile. Salmonella typhimurium and
Salmonella typhi strains were examined to better define
the bile resistance phenotype. The MICs of bile for wild-type
S. typhimurium and S. typhi were 18 and 12%, respectively, and pretreatment of log-phase S. typhimurium with 15% bile dramatically increased bile
resistance. Mutant strains of S. typhimurium and
S. typhi lacking the virulence regulator PhoP-PhoQ were killed at significantly lower bile concentrations than
wild-type strains, while strains with constitutively active PhoP were
able to survive prolonged incubation with bile at concentrations of
>60%. PhoP-PhoQ was shown to mediate resistance specifically to the
bile components deoxycholate and conjugated forms of
chenodeoxycholate, and the protective effect was not generalized to
other membrane-active agents. Growth of both S. typhimurium and S. typhi in bile and in
deoxycholate resulted in the induction or repression of a
number of proteins, many of which appeared identical to
PhoP-PhoQ-activated or -repressed products. The PhoP-PhoQ regulon was
not induced by bile, nor did any of the 21 PhoP-activated or -repressed
genes tested play a role in bile resistance. However, of the
PhoP-activated or -repressed genes tested, two (prgC and
prgH) were transcriptionally repressed by bile in the
medium independent of PhoP-PhoQ. These data suggest that salmonellae
can sense and respond to bile to increase resistance and that this
response likely includes proteins that are members of the PhoP regulon.
These bile- and PhoP-PhoQ-regulated products may play an important role
in the survival of Salmonella spp. in the intestine or gallbladder.
*
Corresponding author. Mailing address: University
of Texas Health Science Center at San Antonio, Department of
Microbiology, 7703 Floyd Curl Dr., San Antonio, TX 78284-7758. Phone:
(210) 567-3973. Fax: (210) 567-6612. E-mail:
gunnj{at}uthscsa.edu.
Infection and Immunity, April 1999, p. 1614-1622, Vol. 67, No. 4
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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