This Article Full Text Full Text (PDF) Other Versions of this Article: AAC.00579-06v1 50/11/3562    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gomez, M. J. Articles by Neyfakh, A. A. Search for Related Content PubMed PubMed Citation Articles by Gomez, M. J. Articles by Neyfakh, A. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2006, p. 3562-3567, Vol. 50, No. 11
0066-4804/06/$08.00+0     doi:10.1128/AAC.00579-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Genes Involved in Intrinsic Antibiotic Resistance of Acinetobacter baylyi ^,

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

Received 10 May 2006/ Returned for modification 13 July 2006/ Accepted 10 August 2006

Bacterial genes defining intrinsic resistance to antibiotics encode proteins that can be targeted by antibiotic potentiators. To find such genes, a transposon insertion library of Acinetobacter baylyi was screened with subinhibitory concentrations of various antibiotics to find supersusceptible mutants. A DNA microarray printer was used to replica plate 10,000 individual library clones to select mutants unable to grow at 1/10 the MICs of 12 different antibiotics. Transposon insertions in 11 genes were found to cause an eightfold or higher hypersusceptibility to at least one antibiotic. Most of the mutants identified exhibited hypersusceptibility to ß-lactam antibiotics. These included 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, and ACIAD0795) can also render cells hypersusceptible to ß-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 the bacteria hypersusceptible to ciprofloxacin. Disruption of acrB in Escherichia coli rendered the 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.

Published ahead of print on 28 August 2006.

This paper is dedicated to the memory of Alexander A. Neyfakh, deceased 20 April 2006.

This article has been cited by other articles:

• Tamae, C., Liu, A., Kim, K., Sitz, D., Hong, J., Becket, E., Bui, A., Solaimani, P., Tran, K. P., Yang, H., Miller, J. H. (2008). Determination of Antibiotic Hypersensitivity among 4,000 Single-Gene-Knockout Mutants of Escherichia coli. J. Bacteriol. 190: 5981-5988 [Abstract] [Full Text]  
• Park, J. T., Uehara, T. (2008). How Bacteria Consume Their Own Exoskeletons (Turnover and Recycling of Cell Wall Peptidoglycan). Microbiol. Mol. Biol. Rev. 72: 211-227 [Abstract] [Full Text]  
• Chakravorty, A., Klovstad, M., Peterson, G., Lindeman, R. E., Gregg-Jolly, L. A. (2008). Sensitivity of an Acinetobacter baylyi mpl Mutant to DNA Damage. Appl. Environ. Microbiol. 74: 1273-1275 [Abstract] [Full Text]  
• Herve, M., Boniface, A., Gobec, S., Blanot, D., Mengin-Lecreulx, D. (2007). Biochemical Characterization and Physiological Properties of Escherichia coli UDP-N-Acetylmuramate:L-Alanyl-{gamma}-D-Glutamyl-meso- Diaminopimelate Ligase. J. Bacteriol. 189: 3987-3995 [Abstract] [Full Text]