[Biochemical and genetic mechanisms for bacteria to acquire aminoglycoside antibiotic resistance]

Abstract

Aminoglycoside (AG)-modifying enzymes are the major biochemical basis for the AG resistance of clinically-occurring bacteria. Recent AG resistance profiles can be characterized by the involvement of AAC(6') in combination with other modifying enzymes in Gram negative bacteria. AAC(6')/APH(2") in Staphylococcus aureus is also remarkable. Genetic basis for the emergence or alteration of AG resistance profiles includes point mutations in the regulatory region or specific sites of the coding region of AG-modifying enzyme genes, and rearrangement of the genes caused by transposon and/or integron. In addition, semisynthetic AG antibiotics such as amikacin, arbekacin (ABK) and isepamicin were also reviewed for their stability to AG-modifying enzymes. ABK that has been widely used as an anti-MRSA drug in Japan is distinct from the other AGs because its monoacetylated derivatives (3"-N-acetylABK and 2'-N-acetylABK) by AG acetyltransferases, AAC(3) and AAC(2'), respectively, retain clear antibiotic activities. Based on this novel aspect and the lack of modification sites for APH(3') and ANT(4'), ABK should be regarded as the most refractory AG for bacteria to acquire resistance.