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哥伦比亚一家医院中产碳青霉烯酶肺炎克雷伯菌的患者内基因多样性及新型 NTE 平台的鉴定。

Within patient genetic diversity of bla harboring Klebsiella pneumoniae in a Colombian hospital and identification of a new NTE platform.

机构信息

Bacterial Molecular Genetics Laboratory, Universidad El Bosque, Carrera 9 #131A-02, Bogota, Colombia.

Facultad de Medicina y Grupo de Investigación en Enfermedades Infecciosas, Universidad Nacional de Colombia, Bogotá, Colombia.

出版信息

Sci Rep. 2021 Nov 1;11(1):21409. doi: 10.1038/s41598-021-00887-2.

DOI:10.1038/s41598-021-00887-2
PMID:34725422
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8560879/
Abstract

Resistance to carbapenems in Klebsiella pneumoniae has been mostly related with the worldwide dissemination of KPC, largely due to the pandemic clones belonging to the complex clonal (CC) 258. To unravel bla post-endemic clinical impact, here we describe clinical characteristics of 68 patients from a high complexity hospital, and the molecular and genetic characteristics of their 139 bla-K. pneumoniae (KPC-Kp) isolates. Of the 26 patients that presented relapses or reinfections, 16 had changes in the resistance profiles of the isolates recovered from the recurrent episodes. In respect to the genetic diversity of KPC-Kp isolates, PFGE revealed 45 different clonal complexes (CC). MLST for 12 representative clones showed ST258 was present in the most frequent CC (23.0%), however, remaining 11 representative clones belonged to non-CC258 STs (77.0%). Interestingly, 16 patients presented within-patient genetic diversity of KPC-Kp clones. In one of these, three unrelated KPC-Kp clones (ST258, ST504, and ST846) and a bla-K. variicola isolate (ST182) were identified. For this patient, complete genome sequence of one representative isolate of each clone was determined. In K. pneumoniae isolates bla was mobilized by two Tn3-like unrelated platforms: Tn4401b (ST258) and Tn6454 (ST504 and ST846), a new NTEIIe transposon for first time characterized also determined in the K. variicola isolate of this study. Genome analysis showed these transposons were harbored in different unrelated but previously reported plasmids and in the chromosome of a K. pneumoniae (for Tn4401b). In conclusion, in the bla post-endemic dissemination in Colombia, different KPC-Kp clones (mostly non-CC258) have emerged due to integration of the single bla gene in new genetic platforms. This work also shows the intra-patient resistant and genetic diversity of KPC-Kp isolates. This circulation dynamic could impact the effectiveness of long-term treatments.

摘要

肺炎克雷伯菌对碳青霉烯类药物的耐药性主要与全球范围内 KPC 的传播有关，主要是由于属于复杂克隆群（CC）258 的大流行克隆。为了阐明 bla 后流行的临床影响，我们在这里描述了来自一家高复杂性医院的 68 名患者的临床特征，以及他们 139 株bla-K. pneumoniae（KPC-Kp）分离株的分子和遗传特征。在 26 名出现复发或再感染的患者中，16 名患者从反复感染中分离出的分离株的耐药谱发生了变化。关于 KPC-Kp 分离株的遗传多样性，PFGE 显示了 45 个不同的克隆群（CC）。对 12 个代表性克隆的 MLST 显示，ST258 存在于最常见的 CC（23.0%）中，但其余 11 个代表性克隆属于非 CC258 ST（77.0%）。有趣的是，16 名患者的 KPC-Kp 克隆存在患者内遗传多样性。在其中一名患者中，鉴定出了三个不相关的 KPC-Kp 克隆（ST258、ST504 和 ST846）和一株 bla-K. variicola 分离株（ST182）。对于该患者，确定了每个克隆的一个代表性分离株的完整基因组序列。在肺炎克雷伯菌分离株中，bla 由两个不相关的 Tn3 样平台 mobilized：Tn4401b（ST258）和 Tn6454（ST504 和 ST846），这是首次确定的新的 NTEIIe 转座子也在本研究中的 K. variicola 分离株中确定。基因组分析表明，这些转座子位于不同的但以前报道过的质粒和肺炎克雷伯菌的染色体中（对于 Tn4401b）。总之，在哥伦比亚 bla 后流行传播中，由于单个 bla 基因整合到新的遗传平台中，出现了不同的 KPC-Kp 克隆（主要是非 CC258）。这项工作还表明了 KPC-Kp 分离株的患者内耐药性和遗传多样性。这种循环动态可能会影响长期治疗的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540c/8560879/a316e57b9cc7/41598_2021_887_Fig6_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540c/8560879/dbf14c6071b9/41598_2021_887_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540c/8560879/a316e57b9cc7/41598_2021_887_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540c/8560879/c32f84747222/41598_2021_887_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540c/8560879/73df0e8f9b3d/41598_2021_887_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540c/8560879/96ac93872793/41598_2021_887_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540c/8560879/44cdf3e98443/41598_2021_887_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540c/8560879/dbf14c6071b9/41598_2021_887_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/540c/8560879/a316e57b9cc7/41598_2021_887_Fig6_HTML.jpg

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