08 October 2007

DNA damage is not so special after all...

Directed Evolution, SOS
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Since the application of penicillin as a therapeutic antimicrobial agent in 1942 there has been a multitude of additional classes of antibiotics targeting a broad range of chemical structures. Bacteria have managed to acquire some form of resistance to all of these antibiotics.
The SOS response of bacteria is a crucial factor in the development of antibiotic resistance, with the system turned on by DNA damage. Miller et al (2004) has showed that beta-lactam antibiotics, such as vancomycin, that targets penicillin binding proteins (PBPs) and cell wall synthesis, activates the SOS response in bacteria.
The study showed that defective cell wall synthesis activated the SOS response and indicates that DNA damage is not the only factor that turns on this system and initiates antibiotic resistance in bacteria.
Miller, C., Thomsen, L.E., Gaggero, C., Mosseri, R., Ingmer, H., and Cohen, S.N. (2004) SOS response induction by b-lactams and bacterial defense against antibiotic lethality. Science 305: 1629–1631.
Macheboeuf, P., Contreras-Martel, C., Job, V., Dideberg, O., and Dessen, A. (2006) Penicillin Binding proteins: key players in bacterial cell cycle and drug resistance processes. FEMS Microbiol Rev 30: 673-691.