Culebras E, Martínez J L
Servicio de Microbiología, Hospital Clínico San Carlos, Plaza de Cristo Rey s/n, 28048-Madrid, Spain.
Front Biosci. 1999 Jan 1;4:D1-8. doi: 10.2741/culebras.
The expression of the bifunctional aminoglycoside inactivating enzyme 6'-N-aminoglycoside acetyltransferase-2"-O-aminoglycoside phosphotransferase is the most important mechanism of high-level aminoglycoside resistance in Staphylococcus and Enterococcus. The enzyme is unique because it presents two different aminoglycoside-modifying activities located in different regions of the molecule. The gene aac(6')-aph(2") which encodes the synthesis of the enzyme is present in Tn4100-like transposons which are inserted both in R plasmids and the chromosomes of aminoglycoside-resistant isolates. The genetic structure of aac(6')-aph(2")-containing isolates indicates that their origin is not clonal, but plasmid conjugation together with multiple insertion events are in the basis of the rapid spread of aminoglycoside resistance among Gram-positive bacteria. There is not any prevalent genetic linkage of aac(6')-aph(2") with other antibiotic-resistance determinant. However, most methicillin resistant Staphylococcus strains present also high-level aminoglycoside resistance as the consequence of constant antibiotic pressure. This situation could change in the next future with the reported reemergence of gentamicin-susceptible MRSA isolates. Recent data show that inhibitors of eukaryotic protein kinases inhibit as well the aminoglycoside phosphotransferase activity. This effect indicates a common structure for these two families of proteins and opens the possibility for a meaningful survey of inhibitors of 6'-N-aminoglycoside acetyltransferase-2"-O-aminoglycoside phosphotransferase useful in clinical practice.
双功能氨基糖苷失活酶6'-N-氨基糖苷乙酰转移酶-2"-O-氨基糖苷磷酸转移酶的表达是葡萄球菌和肠球菌中高水平氨基糖苷耐药的最重要机制。该酶很独特，因为它在分子的不同区域呈现两种不同的氨基糖苷修饰活性。编码该酶合成的基因aac(6')-aph(2")存在于Tn4100样转座子中，这些转座子插入到R质粒和氨基糖苷耐药分离株的染色体中。含有aac(6')-aph(2")的分离株的遗传结构表明它们并非克隆起源，而是质粒接合以及多次插入事件是氨基糖苷耐药在革兰氏阳性菌中快速传播的基础。aac(6')-aph(2")与其他抗生素耐药决定因素之间不存在任何普遍的遗传联系。然而，由于持续的抗生素压力，大多数耐甲氧西林葡萄球菌菌株也呈现高水平氨基糖苷耐药。随着报道的对庆大霉素敏感的耐甲氧西林金黄色葡萄球菌分离株的再度出现，这种情况在未来可能会改变。最近的数据表明，真核蛋白激酶抑制剂也能抑制氨基糖苷磷酸转移酶的活性。这种效应表明这两类蛋白质具有共同结构，并为在临床实践中对6'-N-氨基糖苷乙酰转移酶-2"-O-氨基糖苷磷酸转移酶抑制剂进行有意义的研究开辟了可能性。
