Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Inouye, Y. et al.

Susceptibility of methicillin-resistant Staphylococcus aureus clinical isolates to various antimicrobial agents. IV. Aminoglycoside-modifying enzyme AAC(6')/APH(2") is responsible for arbekacin-resistance enhanced by bleomycin.

Resistance patterns against various antimicrobial agents including beta-lactams, aminoglycosides, tetracyclines, fluoroquinolones, macrolides were examined for 58 strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated at Hiroshima University Hospital from April to November 1992. All the MRSA strains produced type II-coagulase but not beta-lactamase. Regarding aminoglycoside-modifying enzymes, 7 strains (12%) appeared to be producing aminoglycoside 4',4"-adenyltransferase AAD(4',4") encoded by aadD without coproduction of bifunctional aminoglycoside 6'-acetyltransferase/2"-phosphotransferase AAC(6')/APH(2") encoded by aacA-aphD (referred to as tobramycin-resistant type, TOBr). The remaining 51 strains (88%) were phenotypically producers of both enzymes (i.e., mix-resistant type, Mixr). AAD(4',4"), encoded by aadD which was reported to be closely linked with bleomycin (BLM)-resistance determinant, could be seen in 100% MRSA strains and ca. 90% strains expressed AAC(6')/APH(2"). BLM endowed Mixr-type but not TOBr-type MRSA strain with enhanced resistance to arbekacin (ABK) dose-dependently, presumably by modifying the production of AAC(6')/APH(2"). The manifestation of ABK-resistant phenotype by Mixr-type MRSA required the coexistence of BLM. Therefore, ABK must be administered carefully to cure MRSA infection in patients who have been treated with BLM.[1]

References

Susceptibility of methicillin-resistant Staphylococcus aureus clinical isolates to various antimicrobial agents. IV. Aminoglycoside-modifying enzyme AAC(6')/APH(2") is responsible for arbekacin-resistance enhanced by bleomycin. Inouye, Y., Hashimoto, M., Sugiyama, M., Takesue, Y., Santo, T., Yokoyama, T. Hiroshima J. Med. Sci. (1994) [Pubmed]

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