Amikacin: Uses, Resistance, and Prospects for Inhibition.
Amikacin: Uses, Resistance, and Prospects for Inhibition.
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DOI：
10.3390/molecules22122267
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发表时间：
2017-12-19
期刊：
影响因子：
--
通讯作者：
Tolmasky ME
中科院分区：
文献类型：
--
作者：
Ramirez MS;Tolmasky ME
氨基糖苷类是一组自20世纪40年代以来主要用于治疗广谱细菌感染的抗生素。对这些抗生素的主要耐药机制是氨基糖苷类修饰酶的酶修饰，氨基糖苷类修饰酶分为乙酰转移酶、磷酸转移酶和核苷酸转移酶。为了克服这个问题，在70年代开发了新的半合成氨基糖苷类。最广泛使用的半合成氨基糖苷类是阿米卡星，它对大多数氨基糖苷类修饰酶是难治的。阿米卡星是通过在卡那霉素A的脱氧链霉胺部分的C-1氨基上与1-（−）-γ-氨基-α-羟基丁酰基侧链进行酰化反应合成的。临床上发现的主要阿米卡星耐药机制是氨基糖苷6′-N-乙酰基转移酶Ib [AAC（6′）-Ib]的乙酰化作用，该酶由革兰氏阴性菌的整合子、转座子、质粒和染色体中发现的基因编码。许多努力集中在寻找中和AAC（6′）-Ib的作用和延长阿米卡星的使用寿命的策略。小分子以及复合离子载体-Zn +2或Cu+2被发现抑制乙酰化反应，并诱导携带aac（6′）-Ib基因的细菌表型转化为易感性。一种新的半合成氨基糖苷类抗生素--普拉佐霉素正处于开发的高级阶段，将有助于重新引起人们对这类抗生素的兴趣。
Aminoglycosides are a group of antibiotics used since the 1940s to primarily treat a broad spectrum of bacterial infections. The primary resistance mechanism against these antibiotics is enzymatic modification by aminoglycoside-modifying enzymes that are divided into acetyl-transferases, phosphotransferases, and nucleotidyltransferases. To overcome this problem, new semisynthetic aminoglycosides were developed in the 70s. The most widely used semisynthetic aminoglycoside is amikacin, which is refractory to most aminoglycoside modifying enzymes. Amikacin was synthesized by acylation with the l-(−)-γ-amino-α-hydroxybutyryl side chain at the C-1 amino group of the deoxystreptamine moiety of kanamycin A. The main amikacin resistance mechanism found in the clinics is acetylation by the aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6′)-Ib], an enzyme coded for by a gene found in integrons, transposons, plasmids, and chromosomes of Gram-negative bacteria. Numerous efforts are focused on finding strategies to neutralize the action of AAC(6′)-Ib and extend the useful life of amikacin. Small molecules as well as complexes ionophore-Zn+2 or Cu+2 were found to inhibit the acetylation reaction and induced phenotypic conversion to susceptibility in bacteria harboring the aac(6′)-Ib gene. A new semisynthetic aminoglycoside, plazomicin, is in advance stage of development and will contribute to renewed interest in this kind of antibiotics.
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影响因子：
11.8
作者：
Berning, SE;Cherry, TA;Iseman, MD
通讯作者：
Iseman, MD
影响因子：
11.8
作者：
Boucher, Helen W.;Talbot, George H.;Bartlett, John
通讯作者：
Bartlett, John
DOI：
10.1099/00221287-138-3-551
发表时间：
1992-03-01
期刊：
JOURNAL OF GENERAL MICROBIOLOGY
影响因子：
--
作者：
BUSSE, HJ;WOSTMANN, C;BAKKER, EP
通讯作者：
BAKKER, EP
影响因子：
4.9
作者：
BONGAERTS, GPA;KAPTIJN, GMP
通讯作者：
KAPTIJN, GMP
影响因子：
56.3
作者：
Caminero, Jose A.;Sotgiu, Giovanni;Migliori, Giovanni Battista
通讯作者：
Migliori, Giovanni Battista