Characterisation of blaTEM genes and types of β-lactamase plasmids in Neisseria gonorrhoeae - the prevalent and conserved blaTEM-135 has not recently evolved and existed in the Toronto plasmid from the origin.

Characterisation of blaTEM genes and types of β-lactamase plasmids in Neisseria gonorrhoeae - the prevalent and conserved blaTEM-135 has not recently evolved and existed in the Toronto plasmid from the origin.
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DOI:
10.1186/1471-2334-14-454
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发表时间:
2014-08-22
影响因子:
3.7
通讯作者:
Unemo M
Unemo M
中科院分区:
医学3区
文献类型:
--
作者:
Muhammad I;Golparian D;Dillon JA;Johansson A;Ohnishi M;Sethi S;Chen SC;Nakayama S;Sundqvist M;Bala M;Unemo M

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淋病奈瑟菌的抗微生物药物耐药性(AMR)是全世界关注的一个主要问题。最近,人们担心blatem1基因通过blatem1 -135进化成一种广谱β-内酰胺酶(ESBL),它可以降解包括头孢曲松在内的所有头孢菌素。本研究的目的是表征β-内酰胺酶质粒类型、TEM-135与TEM-1对氨苄西林的降解情况,并进行国际上产β-内酰胺酶淋病奈瑟菌的分子流行病学分型。采用抗生素谱、β-内酰胺酶基因测序、β-内酰胺酶质粒分型和淋病奈瑟菌多抗原序列分型(NG-MAST)对2000 - 2011年在15个国家培养的产生β-内酰胺酶的139株淋病奈瑟菌进行了检测。此外,在加拿大分离到的第一个描述的多伦多质粒(pJD7)、第一个亚洲质粒(pJD4)和非洲质粒(pJD5)中对blaTEM基因进行了测序。采用MALDI-TOF质谱水解法检测TEM-135与TEM-1对氨苄西林的降解情况。在具有125个不同NG-MAST STs的分离株中鉴定出6个不同的blaTEM序列,即blatem1(104个分离株)、blatem1 -135(30个分离株)和4个新的blaTEM序列(5个分离株)。blem -1等位基因仅在非洲和亚洲质粒中发现,而里约热内卢/Toronto质粒均含有blem -135等位基因。最有趣的是,1984年首次发现的淋球菌多伦多质粒(pJD7)也具有高度保守的blaem -135等位基因。与TEM-1相比,TEM-135对氨苄西林的降解在MALDI-TOF质谱水解试验中无法区分。编码TEM-135的blatemm -135最初主要与里约热内卢/Toronto质粒相关,在全球流行的产生β-内酰胺酶的淋球菌菌株中普遍存在。blatemm -135似乎并不像先前假设的那样,是由于一些进化选择压力(例如,世界范围内广泛使用广谱头孢菌素)而最近进化的。相反,本研究表明,从发现的多伦多质粒开始,blatemm -135就存在于该质粒中,并且blatemm -135具有高度保守性(在过去的30年里没有进一步进化)。然而,监测不同blaTEM等位基因的存在、blaTEM-135等位基因的可能进化以及产生β-内酰胺酶的质粒类型的国际研究仍然是必要的。本文的在线版本(doi:10.1186/1471-2334-14-454)包含补充材料,可供授权用户使用。
Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major concern worldwide. It has been recently feared that the blaTEM-1 gene is, via blaTEM-135, evolving into an extended-spectrum β-lactamase (ESBL), which could degrade all cephalosporins including ceftriaxone. The aims of the present study were to characterize the blaTEM genes, types of β-lactamase plasmids, the degradation of ampicillin by TEM-135 compared to TEM-1, and to perform molecular epidemiological typing of β-lactamase-producing N. gonorrhoeae strains internationally. β-lactamase producing N. gonorrhoeae isolates (n = 139) cultured from 2000 to 2011 in 15 countries were examined using antibiograms, blaTEM gene sequencing, β-lactamase plasmid typing, and N. gonorrhoeae multiantigen sequence typing (NG-MAST). Furthermore, the blaTEM gene was sequenced in the first described Toronto plasmid (pJD7), one of the first Asian plasmids (pJD4) and African plasmids (pJD5) isolated in Canada. The degradation of ampicillin by TEM-135 compared to TEM-1 was examined using a MALDI-TOF MS hydrolysis assay. Six different blaTEM sequences were identified (among isolates with 125 different NG-MAST STs), i.e. blaTEM-1 (in 104 isolates), blaTEM-135 (in 30 isolates), and four novel blaTEM sequences (in 5 isolates). The blaTEM-1 allele was only found in the African and Asian plasmids, while all Rio/Toronto plasmids possessed the blaTEM-135 allele. Most interesting, the first described gonococcal Toronto plasmid (pJD7), identified in 1984, also possessed the highly conserved blaTEM-135 allele. The degradation of ampicillin by TEM-135 compared to TEM-1 was indistinguishable in the MALDI-TOF MS hydrolysis assay. blaTEM-135, encoding TEM-135, is predominantly and originally associated with the Rio/Toronto plasmid and prevalent among the β-lactamase producing gonococcal strains circulating globally. blaTEM-135 does not appear, as previously hypothesized, to have recently evolved due to some evolutionary selective pressure, for example, by the extensive use of extended-spectrum cephalosporins worldwide. On the contrary, the present study shows that blaTEM-135 existed in the Toronto plasmid from its discovery and that blaTEM-135 is highly conserved (not further evolved in the past >30 years). Nevertheless, international studies for monitoring the presence of different blaTEM alleles, the possible evolution of the blaTEM-135 allele, and the types of β-lactamase producing plasmids, remain imperative. The online version of this article (doi:10.1186/1471-2334-14-454) contains supplementary material, which is available to authorized users.
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