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PMID: 17909183 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Stimulus-dependent differential regulation in the Escherichia coli PhoQ PhoP system.

Miyashiro T, Goulian M

Abstract

In Escherichia coli, Salmonella, and related bacteria, the PhoQ-PhoP system regulates the expression of a large collection of genes in response to conditions of low magnesium or to the presence of certain antimicrobial peptides. We measured transcription of four PhoP-regulated promoters in E. coli that have significantly different PhoP-binding sites. Surprisingly, three promoters show identical responses to magnesium concentrations that range over four orders of magnitude. By analyzing and testing a simple model of transcriptional regulation, we find an explanation for this puzzle and show that these promoters are indeed differentially regulated at sufficiently high levels of stimulus. We then use this analysis to infer an effective level of phosphorylated PhoP as a function of magnesium stimulus. Our results demonstrate that differential regulation generally depends on the strength of the stimulus and highlight how quantitative analysis of stimulus-response curves can be used to infer properties of cell regulatory circuits that cannot be easily obtained from in vitro measurements.

MeSH Terms
Adenosine Triphosphatases/genetics,metabolism Antimicrobial Cationic Peptides/pharmacology Bacterial Proteins/genetics,metabolism Binding Sites/genetics Escherichia coli/drug effects,genetics,metabolism Escherichia coli Proteins/genetics,metabolism Gene Expression Regulation, Bacterial/drug effects Genes, Bacterial Magnesium/pharmacology Membrane Transport Proteins/genetics,metabolism Mutation Promoter Regions, Genetic Transcription, Genetic/drug effects
Chemicals
Antimicrobial Cationic Peptides Bacterial Proteins Escherichia coli Proteins Membrane Transport Proteins PhoP protein, E coli PhoQ protein, Bacteria ropocamptide Adenosine Triphosphatases MgtA protein, E coli Magnesium
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Miyashiro Tim
Department of Physics, University of Pennsylvania, Philadelphia, PA 19104, USA.
Goulian Mark
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33 references, click to expand
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
Published
2007-10-09
Epub
2007-00-01
Pages
16305-10
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC2042202
Subset
IM
Grants
NIGMS NIH HHS · R01 GM080279 · United States
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