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A Positive Feedback Loop Promotes Transcription Surge That Jump-Starts Salmonella Virulence Circuit
Dongwoo Shin,*Eun-Jin Lee,Henry Huang,Eduardo A. Groisman
The PhoP/PhoQ two-component system is a master regulator ofSalmonella pathogenicity. Here we report that induction of thePhoP/PhoQ system results in an initial surge of PhoP phosphorylation;the occupancy of target promoters by the PhoP protein; and thetranscription of PhoP-activated genes, which then subsides toreach new steady-state levels. This surge in PhoP activity isdue to PhoP positively activating its own transcription, becausea strain constitutively expressing the PhoP protein attainedsteady-state levels of activation asymptotically, without thesurge. The strain constitutively expressing the PhoP proteinwas attenuated for virulence in mice, demonstrating that thesurge conferred by PhoP's positive feedback loop is necessaryto 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, Collegeof Agriculture and Life Sciences, Seoul National University,Seoul, 151-921, Korea.
To whom correspondence should be addresssed. E-mail: groisman{at}borcim.wustl.edu
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