Genes Involved in Intrinsic Antibiotic Resistance of Acinetobacter baylyi
| Autor: | Alexander A. Neyfakh, Maria J. Gomez |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
DNA
Bacterial Transposable element medicine.drug_class Cloning Organism Antibiotics Microbial Sensitivity Tests Biology medicine.disease_cause Microbiology Antibiotic resistance Mechanisms of Resistance Drug Resistance Bacterial Escherichia coli medicine Pharmacology (medical) Gene Oligonucleotide Array Sequence Analysis Antibacterial agent Pharmacology Genetics Acinetobacter Reproducibility of Results biology.organism_classification Anti-Bacterial Agents Infectious Diseases Genes Bacterial Mutation DNA Transposable Elements Efflux Bacteria |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 50:3562-3567 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.00579-06 |
| Popis: | 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 β-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 β-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. |
| Databáze: | OpenAIRE |
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