A positive feedback loop promotes transcription surge that jump-starts Salmonella virulence circuit.
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.
Shin
Dongwoo
D
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.
Lee
Eun-Jin
EJ
Huang
Henry
H
Groisman
Eduardo A
EA
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D025461:Feedback, Physiological; D015964:Gene Expression Regulation, Bacterial; D008274:Magnesium / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D012329:RNA, Bacterial / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012481:Salmonella Infections, Animal / Q000382:microbiology; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D014158:Transcription, Genetic; D014774:Virulence
D001426:Bacterial Proteins; C079792:PhoQ protein, Bacteria; D012329:RNA, Bacterial; D012333:RNA, Messenger; C061064:PhoP protein, Bacteria; D008274:Magnesium