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Infection and Immunity, June 2000, p. 3419-3425, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
The Response Regulator PhoP Is Important for
Survival under Conditions of Macrophage-Induced Stress and
Virulence in Yersinia pestis
Petra C. F.
Oyston,1
Nick
Dorrell,2
Kerstin
Williams,2
Shu-Rui
Li,2,
Michael
Green,1
Richard W.
Titball,1 and
Brendan
W.
Wren2,*
Defence Evaluation and Research Agency,
Salisbury, Wiltshire, SP4 0JQ,1 and
Pathogen Molecular Biology and Biochemistry Unit,
Department of Infectious Diseases, London School of Hygiene and
Tropical Medicine, London, WC1E 7HT,2 United
Kingdom
Received 8 November 1999/Returned for modification 6 January
2000/Accepted 8 March 2000
The two-component regulatory system PhoPQ has been identified in
many bacterial species. However, the role of PhoPQ in regulating virulence gene expression in pathogenic bacteria has been characterized only in Salmonella species. We have identified, cloned, and
sequenced PhoP orthologues from Yersinia pestis,
Yersinia pseudotuberculosis, and Yersinia
enterocolitica. To investigate the role of PhoP in the
pathogenicity of Y. pestis, an isogenic phoP
mutant was constructed by using a reverse-genetics PCR-based strategy.
The protein profiles of the wild-type and phoP mutant
strains, grown at either 28 or 37°C, revealed more than 20 differences, indicating that PhoP has pleiotrophic effects on gene
expression in Y. pestis. The mutant showed a reduced
ability to survive in J774 macrophage cell cultures and under
conditions of low pH and oxidative stress in vitro. The mean lethal
dose of the phoP mutant in mice was increased 75-fold in
comparison with that of the wild-type strain, indicating that the PhoPQ
system plays a key role in regulating the virulence of Y. pestis.
*
Corresponding author. Mailing address: Pathogen
Molecular Biology and Biochemistry Unit, Department of Infectious
Diseases, London School of Hygiene and Tropical Medicine, Keppel St.,
London, WC1E 7HT, United Kingdom. Phone: 44 (0)171 927 2288. Fax: 44 (0)171 636 8739. E-mail: brendan.wren{at}lshtm.ac.uk.

Present address: Academic Department of Surgery, St. Bartholomew's
and the Royal London School of Medicine and Dentistry,
Whitechapel,
London, United
Kingdom.
Infection and Immunity, June 2000, p. 3419-3425, Vol. 68, No. 6
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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