SOS response induction by beta-lactams and bacterial defense against antibiotic lethality.
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.
Department of Genetics, Stanford University, Stanford, CA 94305, USA.
Christine
C
Miller
Line Elnif
LE
Thomsen
Carina
C
Gaggero
Ronen
R
Mosseri
Hanne
H
Ingmer
Stanley N
SN
Cohen
D000667:Ampicillin / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D002473:Cell Wall / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism; D006602:Hexosyltransferases / Q000235:genetics / Q000378:metabolism; D007763:Lac Operon; D002267:Muramoylpentapeptide Carboxypeptidase / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009876:Operon; D046915:Penicillin-Binding Proteins; D046928:Peptidoglycan Glycosyltransferase; D010458:Peptidyl Transferases / Q000235:genetics / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D013014:SOS Response, Genetics; D015398:Signal Transduction; D013696:Temperature; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D001616:beta-Galactosidase / Q000096:biosynthesis; D047090:beta-Lactams / Q000378:metabolism / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; C115181:CitB protein, E coli; D029968:Escherichia coli Proteins; C478704:FtsI protein, E coli; D046915:Penicillin-Binding Proteins; D014157:Transcription Factors; D047090:beta-Lactams; C053139:sulA protein, E coli; D000667:Ampicillin; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D046928:Peptidoglycan Glycosyltransferase; D011494:Protein Kinases; C460095:CitA protein, E coli; D001616:beta-Galactosidase; D002267:Muramoylpentapeptide Carboxypeptidase