title: Antagonism between aminoglycosides and beta-lactams in a methicillin-resistant Staphylococcus aureus isolate involves induction of an aminoglycoside-modifying enzyme.
abstract: We encountered three clinical isolates of methicillin-resistant Staphylococcus aureus which were susceptible to netilmicin and arbekacin in the absence of beta-lactam antibiotics but which were resistant to them in the presence of beta-lactam antibiotics. One of these strains, KU5801, was used to further investigate the antagonism between aminoglycosides and beta-lactam antibiotics. beta-Lactam antibiotics induced bacterial synthesis of aminoglycoside-6'-N-acetyltransferase and 2"-O-phosphotransferase [AAC(6')-APH(2")] in association with decreased antimicrobial activities of aminoglycosides. A 14.4-kb EcoRI fragment that included the genes that control for beta-lactam-inducible aminoglycoside resistance was cloned from a 31-kb conjugative plasmid present in KU5801. Restriction fragment mapping and PCR analysis suggested that a Tn4001-like element containing a gene encoding AAC(6')-APH(2") was located downstream from a truncated blaZ gene. The DNA sequence between blaR1 and a Tn4001-like element was determined. The Tn4001-IS257 hybrid structure was cointegrated into the blaZ gene, and the typical sequences for the termination of transcription were not found between these regions. We deduced that antagonism of aminoglycosides by beta-lactam antibiotics in isolate KU5801 involved transcription of the aac(6')-Ie-aph(2")-Ia gene under the influence of the system regulating penicillinase production.
authors.affiliation: Department of Microbiology, Kitasato University School of Medicine, 1-15-1 Kitasato Sagamihara Kanagawa 228-8555, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Ida
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Okamoto
authors.forename: Masato
authors.initials: M
authors.lastname: Nonoyama
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Irinoda
authors.forename: Mizuyo
authors.initials: M
authors.lastname: Kurazono
authors.forename: Matsuhisa
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000123:Acetyltransferases / Q000096:biosynthesis* / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003227:Conjugation, Genetic; D004336:Drug Antagonism; D024881:Drug Resistance, Bacterial; D005839:Gentamicins; D006801:Humans; D019868:Kanamycin Kinase / Q000096:biosynthesis* / Q000235:genetics; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009428:Netilmicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D047090:beta-Lactams; D009428:Netilmicin; D000123:Acetyltransferases; C056532:aminoglycoside N(6')-acetyltransferase; D019868:Kanamycin Kinase