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Science 8 December 2006:
Vol. 314. no. 5805, pp. 1607 - 1609
DOI: 10.1126/science.1134930
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Reports

A Positive Feedback Loop Promotes Transcription Surge That Jump-Starts Salmonella Virulence Circuit

Dongwoo Shin,* Eun-Jin Lee, Henry Huang, Eduardo A. Groisman{dagger}

The PhoP/PhoQ two-component system is a master regulator of Salmonella pathogenicity. Here we report that induction of the PhoP/PhoQ system results in an initial surge of PhoP phosphorylation; the occupancy of target promoters by the PhoP protein; and the transcription of PhoP-activated genes, which then subsides to reach new steady-state levels. This surge in PhoP activity is due to PhoP positively activating its own transcription, because a strain constitutively expressing the PhoP protein attained steady-state levels of activation asymptotically, without the surge. The strain constitutively expressing the PhoP protein was attenuated for virulence in mice, demonstrating that the surge conferred by PhoP's positive feedback loop is necessary to jump-start Salmonella's virulence program.

Department of Molecular Microbiology, Howard Hughes Medical Institute, Washington University School of Medicine, Campus Box 8230, 660 South Euclid Avenue, St. Louis, MO 63110, USA.

* Present address: Center for Agricultural Biomaterials, College of Agriculture and Life Sciences, Seoul National University, Seoul, 151-921, Korea.

{dagger} To whom correspondence should be addresssed. E-mail: groisman{at}borcim.wustl.edu

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Overcoming H-NS-mediated Transcriptional Silencing of Horizontally Acquired Genes by the PhoP and SlyA Proteins in Salmonella enterica.
J. C. Perez, T. Latifi, and E. A. Groisman (2008)
J. Biol. Chem. 283, 10773-10783
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A negative feedback loop involving small RNAs accelerates Vibrio cholerae's transition out of quorum-sensing mode.
S. L. Svenningsen, C. M. Waters, and B. L. Bassler (2008)
Genes & Dev. 22, 226-238
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Anaplasma phagocytophilum p44 mRNA Expression Is Differentially Regulated in Mammalian and Tick Host Cells: Involvement of the DNA Binding Protein ApxR.
X. Wang, Z. Cheng, C. Zhang, T. Kikuchi, and Y. Rikihisa (2007)
J. Bacteriol. 189, 8651-8659
   Abstract »    Full Text »    PDF »
Crystal Structures of the Receiver Domain of the Response Regulator PhoP from Escherichia coli in the Absence and Presence of the Phosphoryl Analog Beryllofluoride.
P. Bachhawat and A. M. Stock (2007)
J. Bacteriol. 189, 5987-5995
   Abstract »    Full Text »    PDF »
A connector of two-component regulatory systems promotes signal amplification and persistence of expression.
A. Kato, A. Y. Mitrophanov, and E. A. Groisman (2007)
PNAS 104, 12063-12068
   Abstract »    Full Text »    PDF »


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Science. ISSN 0036-8075 (print), 1095-9203 (online)