Rise and dissemination of aminoglycoside resistance: the aac(6')-Ib paradigm.

Rise and dissemination of aminoglycoside resistance: the aac(6')-Ib paradigm.
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DOI:
10.3389/fmicb.2013.00121
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发表时间:
2013
影响因子:
5.2
通讯作者:
Tolmasky ME
Tolmasky ME
中科院分区:
生物学2区
文献类型:
--
作者:
Ramirez MS;Nikolaidis N;Tolmasky ME

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酶修饰是细菌击败抗生素作用的普遍机制。氨基糖苷类药物通常被染色体、质粒和其他遗传元件中存在的基因编码的氨基糖苷类修饰酶灭活。AAC(6′)-Ib(氨基糖苷6′-N-乙酰转移酶Ib型)是在多种革兰氏阴性病原体中发现的具有临床重要性的酶。AAC(6′)-Ib酶之所以引起人们的兴趣,不仅是因为它的普遍存在,而且还因为它的其他特性,它在N-末端呈现显著的微异质性,并且aac(6′)-Ib基因通常存在于整合子、转座子、质粒、基因组岛和其他遗传结构中。在NCBI数据库中,除N-末端高度异质性外,AAC(6′)-Ib相关的条目共有45个,其中32个氨基酸序列不同,但名称相同。虽然一些变体保留了相似的特性,但其他变体在特异性方面显示出显著差异,包括介导环丙沙星乙酰化的AAC(6′)-Ib-cr的情况,这代表了抗性酶获得利用不同类别的抗生素作为底物的能力的罕见情况。目前正在努力利用反义技术来关闭基因的表达或鉴定酶抑制剂以诱导表型转化为易感性。
Enzymatic modification is a prevalent mechanism by which bacteria defeat the action of antibiotics. Aminoglycosides are often inactivated by aminoglycoside modifying enzymes encoded by genes present in the chromosome, plasmids, and other genetic elements. The AAC(6′)-Ib (aminoglycoside 6′-N-acetyltransferase type Ib) is an enzyme of clinical importance found in a wide variety of gram-negative pathogens. The AAC(6′)-Ib enzyme is of interest not only because of his ubiquity but also because of other characteristics, it presents significant microheterogeneity at the N-termini and the aac(6′)-Ib gene is often present in integrons, transposons, plasmids, genomic islands, and other genetic structures. Excluding the highly heterogeneous N-termini, there are 45 non-identical AAC(6′)-Ib related entries in the NCBI database, 32 of which have identical name in spite of not having identical amino acid sequence. While some variants conserved similar properties, others show dramatic differences in specificity, including the case of AAC(6′)-Ib-cr that mediates acetylation of ciprofloxacin representing a rare case where a resistance enzyme acquires the ability to utilize an antibiotic of a different class as substrate. Efforts to utilize antisense technologies to turn off expression of the gene or to identify enzymatic inhibitors to induce phenotypic conversion to susceptibility are under way.
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