Role of aminoglycoside 6 '-acetyltransferase in a novel multiple aminoglycoside resistance of an actinomycete strain #8: Inactivation of aminoglycosides with 6 '-amino group except arbekacin and neomycin

From a rare actinomycete strain #8 isolated from soil as arbekacin (ABK) re sistant, we cloned a gene segment (0.9 kb) conferring multiple resistance t o aminoglycoside (AG) antibiotics with 6'-NH2 including semisynthetic ones except ABK and neomycin (NM). Enzymatic modification using cell free extrac ts from Streptomyces lividans TK21/pANT-S2 carrying the cloned gene reveale d that the gene coded for an AG 6'-acetyltransferase [AAC(6')] capable of a cetylating all of the tested AGs with 6'-NH2 including semisynthetic ones a nd astromicin. The substrate specificty of the enzyme was thus similar to t hat of AAC(6')-Ie of Enterococcus faecalis. Antibiotic assay revealed a wea k but clear antibiotic activity of 6'-N-acetylABK (8% of ABK activity) in c ontrast with substantial inactivation by the AAC(6') of the other AGs inclu ding amikacin and isepamicin. The NM acetylation by the AAC(6') also did no t result in NM inactivation. It seems thus likely that AAC(6')-dependent re sistance to ABK and NM, if it emerges, will remain at low level.