The ard1 gene from Streptomyces capreolus encodes a polypeptide of the ABC-transporters superfamily which confers resistance to the aminonucleoside antibiotic A201A

Abstract

A gene (ard1) encoding resistance to the aminonucleoside antibiotic A201A was cloned from Streptomyces capreolus NRRL 3817, the producing organism, and expressed in Streptomyces lividans. The gene ard1 induced antibiotic resistance that was highly specific for A201A. The nucleotide sequence of ard1 contains an open reading frame of 1677 bp. Transcription initiation was found to take place approximately 86 nucleotides preceding the ATG translation-initiation codon, indicating that ard1 is transcribed from its own promoter. The deduced protein sequence (Ard1, 558 amino acids) presents two ATP-binding domains with significant similarities to those of the ATP-binding cassette transporters (ABC-transporters) superfamily, including some that confer drug resistance in a variety of antibiotic-producing Streptomyces, other Gram-positive bacteria and eukaryotic cells. As is probably the case for most of these proteins, the mechanism of A201A resistance conferred by Ard1 is an active efflux energized by ATP hydrolysis.