PMID:15308764

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Citation

Miller, C, Thomsen, LE, Gaggero, C, Mosseri, R, Ingmer, H and Cohen, SN (2004) SOS response induction by beta-lactams and bacterial defense against antibiotic lethality. Science 305:1629-31

Abstract

The SOS response aids bacterial propagation by inhibiting cell division during repair of DNA damage. We report that inactivation of the ftsI gene product, penicillin binding protein 3, by either beta-lactam antibiotics or genetic mutation induces SOS in Escherichia coli through the DpiBA two-component signal transduction system. This event, which requires the SOS-promoting recA and lexA genes as well as dpiA, transiently halts bacterial cell division, enabling survival to otherwise lethal antibiotic exposure. Our findings reveal defective cell wall synthesis as an unexpected initiator of the bacterial SOS response, indicate that beta-lactam antibiotics are extracellular stimuli of this response, and demonstrate a novel mechanism for mitigation of antimicrobial lethality.

Links

PubMed Online version:10.1126/science.1101630

Keywords

Ampicillin/pharmacology; Anti-Bacterial Agents/metabolism; Anti-Bacterial Agents/pharmacology; Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Division; Cell Wall/metabolism; Escherichia coli/drug effects; Escherichia coli/genetics; Escherichia coli/metabolism; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Hexosyltransferases/genetics; Hexosyltransferases/metabolism; Lac Operon; Muramoylpentapeptide Carboxypeptidase/genetics; Muramoylpentapeptide Carboxypeptidase/metabolism; Mutation; Operon; Penicillin-Binding Proteins; Peptidoglycan Glycosyltransferase; Peptidyl Transferases/genetics; Peptidyl Transferases/metabolism; Protein Kinases/genetics; Protein Kinases/metabolism; SOS Response (Genetics); Signal Transduction; Temperature; Transcription Factors/genetics; Transcription Factors/metabolism; beta-Galactosidase/biosynthesis; beta-Lactams/metabolism; beta-Lactams/pharmacology

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