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Science 305 (5690): 1629-1631

Copyright © 2004 by the American Association for the Advancement of Science

SOS Response Induction by ß-Lactams and Bacterial Defense Against Antibiotic Lethality

Christine Miller,1 Line Elnif Thomsen,2 Carina Gaggero,1* Ronen Mosseri,1{dagger} Hanne Ingmer,1,2{ddagger} Stanley N. Cohen1§

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 ß-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 ß-lactam antibiotics are extracellular stimuli of this response, and demonstrate a novel mechanism for mitigation of antimicrobial lethality.

1 Department of Genetics, Stanford University, Stanford, CA 94305, USA.
2 Department of Veterinary Pathobiology, Royal Veterinary and Agricultural University, Stigboejlen 4, Fredericksberg C, DK-1870, Denmark.

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* Present address: Departamento de Biologia Molecular, Instituto de Investigaciones Biológicas Clemente Estable, Av. Italia 3318, 11600 Montevideo, Uruguay.

{dagger} Present address: Department of Pediatrics B, Schneider Children's Medical Center of Israel, Petah Tiqva 49202, Israel.

{ddagger} Present address: Department of Veterinary Pathobiology, Royal Veterinary and Agricultural University, Stigboejlen 4, Frederiksberg C, DK-1870, Denmark.

§ To whom correspondence should be addressed. E-mail: sncohen{at}stanford.edu

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