AAC Accepts, published online ahead of print on 28 August 2006

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Antimicrob. Agents Chemother. doi:10.1128/AAC.00579-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Identification of Genes Involved in Intrinsic Antibiotic Resistance of Acinetobacter baylyi

Maria J. Gomez^* and Alexander A. Neyfakh

Center for Pharmaceutical Biotechnology, University of Illinois, Chicago, Illinois 60607

^* To whom correspondence should be addressed. Email: jgomez6{at}uic.edu,

Bacterial genes defining intrinsic resistance to antibiotics encode proteins that can be targeted by antibiotic potentiators. For finding such genes, a transposon insertion library of Acinetobacter baylyi was screened at subinhibitory concentrations of various antibiotics to find super-susceptible mutants. A DNA microarray printer was used to replica plate 10,000 individual library clones to select mutants unable to grow at 1/10 of MIC of twelve different antibiotics. Transposon insertions in eleven genes were found to cause an 8-fold or higher hypersusceptibility to at least one antibiotic. Most of the identified mutants exhibited hypersusceptibility to -lactam antibiotics. These include mutants with disruptions of genes encoding proteins involved in efflux (acrB and oprM) as well as genes pertaining to peptidoglycan synthesis and modification ampD, mpl, and pbpG. However, disruptions of genes encoding proteins with seemingly unrelated functions (gph, argH, hisF) can also render cells hypersusceptible to -lactam antibiotics. A knockout of gshA, involved in glutathione biosynthesis, enhanced the susceptibility to metronidazole, while a knockout of recD, involved in recombination and repair, made bacteria hypersusceptible to ciprofloxacin. Disruption of acrB in Escherichia coli rendered cells hypersusceptible to several antibiotics. However, knockout mutants of other homologous genes in E. coli showed no significant changes in antibiotic MICs indicating that the intrinsic resistance genes are species-specific.

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