title: Double stage activity in aminoglycoside antibiotics.
abstract: Fourteen different aminoglycoside antibiotics (AGs) were challenged with aminoglycoside acetyltransferases (AACs) of actinomycete origin in order to examine their 'double stage activity' that is arbitrarily defined as antibiotic activity retainable after enzymatic modification. In kanamycin (KM)-group AGs tested [KM, dibekacin (DKB), amikacin and arbekacin (ABK)], ABK retained activity after acetylations by AAC(3), AAC(2') and AAC(6'). DKB also retained a weak activity after acetylation by AAC(2'). In gentamicin (GM)-group AGs tested [GM, micronomicin, sisomicin (SISO), netilmicin (NTL) and isepamicin], GM, SISO and NTL retained activites after acetylation by AAC(2'). In neomycin (NM)-group AGs tested [ribostamycin, NM, paromomycin], NM retained activity after acetylation by AAC(6') and AAC(2'). None of astromicin (ASTM)-group AGs tested (ASTM and istamycin B) retained activity after acetylation by AAC(2') and AAC(6'). The activities of acetylated ABK derivatives by AAC(3) and AAC(2') were distinctively high, compared to the others. Streptomyces lividans TK21 containing the cloned aac genes were markedly sensitive to AGs that retained activities after acetylation, indicating the substantial effect of 'double stage activity'.
authors.affiliation: National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hotta
authors.forename: A
authors.initials: A
authors.lastname: Sunada
authors.forename: Y
authors.initials: Y
authors.lastname: Ikeda
authors.forename: S
authors.initials: S
authors.lastname: Kondo
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000192:Actinomycetales / Q000378:metabolism*; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects*; D002240:Carbohydrate Sequence; D002855:Chromatography, Thin Layer; D004352:Drug Resistance, Microbial; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D013302:Streptomyces / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000123:Acetyltransferases; C019681:aminoglycoside acetyltransferase