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产 NDM-1 和 KPC-3 碳青霉烯酶的克吕沃尔菌属:在葡萄牙研究肠杆菌科 bla 基因的遗传异质性和获得途径。

Emergence of NDM-1 and KPC-3 carbapenemases in Kluyvera cryocrescens: Investigating genetic heterogeneity and acquisition routes of bla in Enterobacterales species in Portugal.

机构信息

UCIBIO - Applied Molecular Biosciences Unit, Faculty of Pharmacy, University of Porto, Porto, Portugal; Associate Laboratory i4HB - Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, Porto, Portugal.

Service of Clinical Pathology, Hospital University Centre São João, Porto, Portugal.

出版信息

J Glob Antimicrob Resist. 2023 Sep;34:195-198. doi: 10.1016/j.jgar.2023.07.008. Epub 2023 Jul 17.

DOI:10.1016/j.jgar.2023.07.008
PMID:37468064
Abstract

OBJECTIVES

A higher diversity of species, clones and genes have been increasingly implicated in carbapenemases spread, though the mobile genetic elements responsible for their acquisition and dispersion at local and global levels are less explored, particularly in species other than Klebsiella pneumoniae or Escherichia coli. We aim to explain the emergence of NDM-1 and KPC-3 carbapenemases in a Kluyvera cryocrescens isolate, and to shed light on the heterogeneity of genetic platforms and acquisition routes of bla in diverse Enterobacterales species in Portugal.

METHODS

A KPC-3 and NDM-1-producing K. cryocrescens colonizing a hospitalized patient in 2019 was characterized by whole-genome sequencing and antibiotic resistance profiling following standard methods. Conjugative transfer of carbapenemases genes was assessed by filter mating. Plasmids were reconstructed with in silico and in vitro approaches. bla genetic context was compared with that of diverse NDM-1-producing Enterobacterales species, previously described in Portugal.

RESULTS

K. cryocrescens K629 showed a multidrug resistance profile. Resistance gene bla was harboured by a Tn4401d transposon within a worldwide-spread IncN-ST15 plasmid (pKLU-KPC3), whereas bla was located in a Tn3000 within a non-typeable mosaic plasmid (pKLU-NDM1). The heterogeneous bla genetic platforms and variable plasmid backbones identified in various Enterobacterales species suggested multiple introductions of bla in Portugal, mediated by variable insertion sequences.

CONCLUSIONS

We report the convergence of KPC-3 and NDM-1 in K. cryocrescens and the variable dissemination modes of these carbapenemases in different Enterobacterales species, underlining the need to track down genetic platforms responsible for carbapenemases diffusion.

摘要

目的

越来越多的物种、克隆和基因多样性与碳青霉烯酶的传播有关,尽管负责在本地和全球水平获得和传播它们的可移动遗传元件研究较少,特别是在除肺炎克雷伯菌或大肠杆菌以外的物种中。我们旨在解释在一株克鲁维酵母属中分离出的 NDM-1 和 KPC-3 碳青霉烯酶的出现,并阐明葡萄牙不同肠杆菌科物种中 bla 的遗传平台和获得途径的异质性。

方法

通过全基因组测序和标准方法对 2019 年定植于住院患者的一株产 KPC-3 和 NDM-1 的克鲁维酵母属进行了特征描述。通过滤膜交配评估碳青霉烯酶基因的接合转移。通过计算机模拟和体外方法构建质粒。将 bla 的遗传背景与之前在葡萄牙描述的不同产 NDM-1 的肠杆菌科物种进行比较。

结果

克鲁维酵母属 K629 表现出多药耐药性。耐药基因 bla 位于一个在全球范围内传播的 IncN-ST15 质粒(pKLU-KPC3)内的 Tn4401d 转座子中,而 bla 位于一个非可分型镶嵌质粒(pKLU-NDM1)内的 Tn3000 中。在不同肠杆菌科物种中发现的 bla 遗传平台的异质性和可变质粒骨架表明,bla 在葡萄牙的多次引入是由不同的插入序列介导的。

结论

我们报告了 K. cryocrescens 中 KPC-3 和 NDM-1 的融合,以及这些碳青霉烯酶在不同肠杆菌科物种中的不同传播模式,这突显出需要追踪负责碳青霉烯酶扩散的遗传平台。

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