Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance Export

@article{citeulike:315764, abstract = {The emergence of drug-resistant bacteria poses a serious threat to human health. In the case of several antibiotics, including those of the quinolone and rifamycin classes, bacteria rapidly acquire resistance through mutation of chromosomal genes during therapy. In this work, we show that preventing induction of the SOS response by interfering with the activity of the protease LexA renders pathogenic Escherichia coli unable to evolve resistance in vivo to ciprofloxacin or rifampicin, important quinolone and rifamycin antibiotics. We show in vitro that LexA cleavage is induced during RecBC-mediated repair of ciprofloxacin-mediated DNA damage and that this results in the derepression of the SOS-regulated polymerases Pol II, Pol IV and Pol V, which collaborate to induce resistance-conferring mutations. Our findings indicate that the inhibition of mutation could serve as a novel therapeutic strategy to combat the evolution of antibiotic resistance.}, address = {Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA.}, author = {Cirz, Ryan T. and Chin, Jodie K. and Andes, David R. and de Cr\'{e}cy-Lagard, Val\'{e}rie and Craig, William A. and Romesberg, Floyd E.}, citeulike-article-id = {315764}, citeulike-linkout-0 = {http://dx.doi.org/10.1371/journal.pbio.0030176}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/15869329}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=15869329}, day = {10}, doi = {10.1371/journal.pbio.0030176}, issn = {1545-7885}, journal = {PLoS Biol}, keywords = {antibiotic}, month = {May}, number = {6}, pages = {e176+}, posted-at = {2009-11-08 05:57:26}, priority = {2}, publisher = {Public Library of Science}, title = {Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance}, url = {http://dx.doi.org/10.1371/journal.pbio.0030176}, volume = {3}, year = {2005} }

TY - JOUR ID - citeulike:315764 L3 - citeulike-article-id:315764 N2 - The emergence of drug-resistant bacteria poses a serious threat to human health. In the case of several antibiotics, including those of the quinolone and rifamycin classes, bacteria rapidly acquire resistance through mutation of chromosomal genes during therapy. In this work, we show that preventing induction of the SOS response by interfering with the activity of the protease LexA renders pathogenic Escherichia coli unable to evolve resistance in vivo to ciprofloxacin or rifampicin, important quinolone and rifamycin antibiotics. We show in vitro that LexA cleavage is induced during RecBC-mediated repair of ciprofloxacin-mediated DNA damage and that this results in the derepression of the SOS-regulated polymerases Pol II, Pol IV and Pol V, which collaborate to induce resistance-conferring mutations. Our findings indicate that the inhibition of mutation could serve as a novel therapeutic strategy to combat the evolution of antibiotic resistance. IS - 6 JF - PLoS Biol SN - 1545-7885 AD - Department of Chemistry, The Scripps Research Institute, La Jolla, California, USA. TI - Inhibition of Mutation and Combating the Evolution of Antibiotic Resistance PB - Public Library of Science VL - 3 SP - e176 KW - antibiotic AU - Cirz, Ryan AU - Chin, Jodie AU - Andes, David AU - de Crécy-Lagard, Valérie AU - Craig, William AU - Romesberg, Floyd PY - 2005/05/10/ UR - http://dx.doi.org/10.1371/journal.pbio.0030176 ER -