Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran.
Department of Microbiology, Faculty of Biological Sciences, Alzahra University, Tehran, Iran.
PLoS One. 2023 Nov 16;18(11):e0292288. doi: 10.1371/journal.pone.0292288. eCollection 2023.
Carbapanem-resistant Klebsiella pneumoniae is a globally healthcare crisis. The distribution of plasmids carrying carbapenemase genes among K. pneumoniae poses a serious threat in clinical settings. Here, we characterized the genetic structure of plasmids harboring major carbapenemases (e.g. blaKPC, blaNDM, blaOXA-48-like, and blaGES) from K. pneumoniae using bioinformatics tools. The plasmids carrying at least one major carbapenemase gene were retrieved from the GenBank database. The DNA length, Inc type, and conjugal apparatus of these plasmids were detected. Additionally, allele types, co-existence, co-occurrence of carbapenemase genes, gene repetition, and sequence types of isolates, were characterized. There were 2254 plasmids harboring carbapenemase genes in the database. This study revealed that blaKPC-2, blaNDM-1, blaOXA-48, and blaGES-5 were the most prevalent allele types. Out of 1140 (50%) plasmids were potentially conjugative. IncFII, IncR, IncX3, and IncL replicon types were predominant. The co-existence analysis revealed that the most prevalent of other resistance genes were blaTEM-1 (related to blaKPC), blaOXA-232 (related to blaOXA-48), bleMBL (related to blaNDM), and aac (6')-Ib4 (related to blaGES). The co-occurrence of carbapenemases was detected in 42 plasmids while 15 plasmids contained carbapenemase gene repetitions. Sequence alignments highlighted that plasmids carrying blaKPC and blaOXA-48-like were more homogeneous whereas the plasmids carrying blaNDM were divergent. It seems that K. pneumoniae utilizes diversity of genetic flexibility and recombination for resistance against carbapenems. The genetic structure of the plasmids showed that class I and III, Tn3 family, Tn5403 family derivatives, and Tn7-like elements were strongly associated with carbapenemases. The mobilizable plasmids carrying carbapenemases play an important role in the spread of these genes. In addition, gene repetition maybe is related to carbapenem heteroresistance. According to MST (minimum spanning tree) results, the majority of plasmids belonged to sequence type (ST) 11, ST14, and ST12. These international clones have a high capacity to acquire the carbapenemase-containing plasmids.
耐碳青霉烯类肺炎克雷伯菌是全球医疗保健危机。肺炎克雷伯菌中携带碳青霉烯酶基因的质粒的分布在临床环境中构成了严重威胁。在这里，我们使用生物信息学工具对来自肺炎克雷伯菌的携带主要碳青霉烯酶（如 blaKPC、blaNDM、blaOXA-48 样和 blaGES）的质粒的遗传结构进行了表征。从 GenBank 数据库中检索到至少携带一种主要碳青霉烯酶基因的质粒。检测了这些质粒的 DNA 长度、Inc 类型和接合装置。此外，还对分离株的等位基因类型、碳青霉烯酶基因的共存、共存、基因重复和序列类型进行了表征。数据库中有 2254 个携带碳青霉烯酶基因的质粒。本研究表明，blaKPC-2、blaNDM-1、blaOXA-48 和 blaGES-5 是最常见的等位基因类型。在 1140 个（50%）质粒中可能是可接合的。IncFII、IncR、IncX3 和 IncL 复制子类型占主导地位。共存分析表明，最常见的其他耐药基因是 blaTEM-1（与 blaKPC 相关）、blaOXA-232（与 blaOXA-48 相关）、bleMBL（与 blaNDM 相关）和 aac（6'）-Ib4（与 blaGES 相关）。在 42 个质粒中检测到碳青霉烯酶的共存，而 15 个质粒包含碳青霉烯酶基因重复。序列比对突出显示，携带 blaKPC 和 blaOXA-48 样的质粒更同质，而携带 blaNDM 的质粒则更分散。似乎肺炎克雷伯菌利用遗传灵活性和重组的多样性来抵抗碳青霉烯类药物。质粒的遗传结构表明，I 类和 III 类、Tn3 家族、Tn5403 家族衍生物和 Tn7 样元件与碳青霉烯酶密切相关。携带碳青霉烯酶的可移动质粒在这些基因的传播中起着重要作用。此外，基因重复可能与碳青霉烯类异质性耐药有关。根据 MST（最小生成树）结果，大多数质粒属于 ST11、ST14 和 ST12 序列型。这些国际克隆具有获得携带碳青霉烯酶质粒的高能力。
