SECONDARY AMINOGLYCOSIDE RESISTANCE IN AMINOGLYCOSIDE-PRODUCING STRAINS OF STREPTOMYCES

The role of aminoglycoside (AG) acetyltransferases (AACs) and of the corresponding genes in resistance to foreign AGs in AG-producing strains of Streptomyces were studied. The research focussed on (i) the activation mechanism of the cryptic kanamycin(Km)-resistance-encoding gene that encodes an AAC(3) in streptomycin-producing S. griseus SS-1198, and (ii) an AAC(2') with novel activity and substrate specificity in kasugamycin-producing S. kasugaensis MB273. Activation of the cryptic kan gene in S. griseus SS-1198 is probably due to a single base substitution at the putative - 10 promoter region, leading to the enhancement of transcription, resulting in resistance to AG. The coding region of the kan gene was highly homologous to that of the aacC7 gene of paromomycin-producing S. rimosus forma paromomycinus. On the other hand, resistance in S. kasugaensis MB273 was found to be due to an AAC(2') capable of acetylating astromicin group AGs at two different sites (I-NH2 with istamycin B, and 2'-NH2 with astromicin and istamycin A). These additional antibiotic resistances that are independent of a self-resistance basis may be regarded as 'secondary' resistances, so as to distinguish them from 'primary' resistances arising from a self-resistance basis.