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不动杆菌属中氨基糖苷类耐药的分子流行病学

Molecular epidemiology of aminoglycoside resistance in Acinetobacter spp.

作者信息

Seward R J, Lambert T, Towner K J

机构信息

Department of Microbiology, University Hospital, Queen's Medical Centre, Nottingham.

出版信息

J Med Microbiol. 1998 May;47(5):455-62. doi: 10.1099/00222615-47-5-455.

Abstract

Most aminoglycoside resistance in Acinetobacter spp. involves production of aminoglycoside-modifying enzymes. Previous studies have shown that the genes encoding these enzymes can be present on plasmids, transposons or within integron-type structures. To determine whether particular mechanisms of aminoglycoside resistance have developed in strains from specific geographical locations (with subsequent clonal spread), or whether common mechanisms have been acquired by genotypically distinct clinical isolates of Acinetobacter spp. throughout the world, a genotypically heterogeneous collection of 24 multiresistant clinical isolates of Acinetobacter spp. from 15 hospitals in 11 countries worldwide was studied. All were resistant to two or more aminoglycoside antibiotics. The full aminoglycoside resistance profile was determined for each isolate, allowing a putative enzyme content to be inferred, with subsequent confirmation of enzyme content and genetic location by polymerase chain reaction (PCR) and hybridisation techniques. All produced at least one aminoglycoside-modifying enzyme, most commonly AAC(3)-I and ANT(3'')-I in various combinations. Other enzymes found were AAC(3)-II, AAC(6')-I, ANT(2''), APH(3')-I and APH(3')-VI. None was confined to strains from a particular geographical area. Nine isolates transferred resistance mediated by AAC(3)-I, ANT(2'')-I, APH(3')-I or APH(3)'-VI by conjugation to a sensitive strain of A. baumannii, but most resistance was non-transferable. PCR mapping revealed an integron location in six isolates for the aac(3)-Ia gene and in three isolates for the ant(3'')-Ia gene. Overall, the study demonstrated that similar aminoglycoside-modifying enzymes are found in unrelated isolates of Acinetobacter spp., and that particular genes are not restricted to specific areas of the world. The demonstration of certain genes on plasmids and integrons emphasises the probable importance of these structures in the dissemination of certain types of aminoglycoside resistance in Acinetobacter spp.

摘要

不动杆菌属中大多数对氨基糖苷类抗生素的耐药性与氨基糖苷类修饰酶的产生有关。先前的研究表明,编码这些酶的基因可存在于质粒、转座子或整合子样结构中。为了确定特定地理位置的菌株中是否已形成特定的氨基糖苷类耐药机制(随后发生克隆传播),或者世界各地基因分型不同的不动杆菌属临床分离株是否已获得共同的耐药机制,我们研究了来自全球11个国家15家医院的24株多耐药临床不动杆菌属分离株,这些分离株在基因分型上具有异质性。所有菌株均对两种或更多种氨基糖苷类抗生素耐药。确定了每个分离株完整的氨基糖苷类耐药谱,据此推断出假定的酶含量,随后通过聚合酶链反应(PCR)和杂交技术确认酶含量和基因位置。所有菌株均产生至少一种氨基糖苷类修饰酶,最常见的是不同组合的AAC(3)-I和ANT(3'')-I。发现的其他酶有AAC(3)-II、AAC(6')-I、ANT(2'')、APH(3')-I和APH(3')-VI。没有一种酶局限于来自特定地理区域的菌株。9株分离株通过接合作用将由AAC(3)-I、ANT(2'')-I、APH(3')-I或APH(3')-VI介导的耐药性转移至鲍曼不动杆菌的敏感菌株,但大多数耐药性不可转移。PCR定位显示,6株分离株的aac(3)-Ia基因位于整合子中,3株分离株的ant(3'')-Ia基因位于整合子中。总体而言,该研究表明,在不相关的不动杆菌属分离株中发现了相似的氨基糖苷类修饰酶,并且特定基因并不局限于世界上的特定区域。在质粒和整合子上发现某些基因,这强调了这些结构在不动杆菌属中某些类型氨基糖苷类耐药性传播中的可能重要性。

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