Resistance of Pseudomonas aeruginosa PAO to nalidixic acid and low levels of beta-lactam antibiotics: mapping of chromosomal genes.
Resistance to high concentrations of nalidixic acid in Pseudomonas aeruginosa PAO was due to mutations in one locus designated nalA, which was mapped by transduction between hex-9001 and leu-10. The nalA mutants were cross-resistant to pipemidic acid, a nalidixic acid analog, at relatively low concentrations. Replicative DNA synthesis was resistant to both drugs in permeabilized cells of nalA mutants. A locus coding for low-level resistance to nalidixic acid, nalB, was cotransducible with pyrB, proC, and met-28. The nalB mutants were also resistant to low levels of pipemidic acid, novobiocin, and beta-lactam antibiotics (e.g., carbenicillin, azlocillin, and cefsulodin), but not to other drugs, such as gentamicin, rifampin, kanamycin, or tetracycline. In nalB mutants, DNA replication showed wild-type sensitivity to nalidixic acid, whereas carbenicillin-induced filamentation required higher drug levels than in the wild-type strain. Thus, nalB mutations appear to decrease cell permeability to some antibiotics. The sensitivity of replicative DNA synthesis to nalidixic acid and novobiocin was very similar in P. aeruginosa and Escherichia coli; by contrast, the concentrations of these drugs needed to inhibit growth of P. aeruginosa were higher than those reported for E. coli by one or two orders of magnitude.
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002228:Carbenicillin / Q000494:pharmacology; D002874:Chromosome Mapping; D004269:DNA, Bacterial / Q000096:biosynthesis; D004926:Escherichia coli / Q000187:drug effects; D005798:Genes, Bacterial; D009154:Mutation; D009268:Nalidixic Acid / Q000494:pharmacology*; D009675:Novobiocin / Q000494:pharmacology; D010403:Penicillin Resistance; D010876:Pipemidic Acid / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D009675:Novobiocin; D009268:Nalidixic Acid; D002228:Carbenicillin; D010876:Pipemidic Acid