1887

Abstract

Spontaneous multidrug-resistant (Mdr) mutants of strain ECL8 arose at a frequency of 2-2 ° 10 and showed increased resistance to a range of unrelated antibiotics, including chloramphenicol, tetracycline, nalidixic acid, ampicillin, norfloxacin, trimethoprim and puromycin. A chromosomal fragment from one such mutant was cloned, and found to confer an Mdr phenotype on K12 cells that was essentially identical to that of the mutant. Almost complete loss of the OmpF porin in the transformant, and of the corresponding porin in the mutant, was observed. The presence of the Mdr mutation in or the cloned antibiotic ) locus in also resulted in active efflux of tetracycline, and increased active efflux of chloramphenicol. After transformation of a plasmid into expression of chloramphenicol resistance occurred later than expression of resistance to tetracycline, puromycin, trimethoprim and nalidixic acid. The gene was localized and sequenced. It encodes a putative positive transcriptional activator that is weakly related to the MarA and SoxS proteins. A gene was also found to be present in an fragment that has previously been shown to confer an Mdr phenotype, and it appears that , rather than the gene identified in that study, is responsible for multidrug resistance. The gene from the wild-type was identical to that of the mutant strain and also conferred an Mdr phenotype on indicating that the mutation responsible for Mdr in had not been cloned.

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1995-08-01
2021-08-04
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