The emergence of highly resistant and hypervirulent Klebsiella pneumoniae CC14 clone in a tertiary hospital over 8 years

IF 10.4 1区 生物学 Q1 GENETICS & HEREDITY Genome Medicine Pub Date : 2024-04-18 DOI:10.1186/s13073-024-01332-5
Sharif Hala, Mohammed Malaikah, Jiayi Huang, Wesam Bahitham, Omniya Fallatah, Samer Zakri, Chakkiath Paul Antony, Mohammed Alshehri, Raeece Naeem Ghazzali, Fathia Ben-Rached, Abdullah Alsahafi, Asim Alsaedi, Ghadeer AlAhmadi, Mai Kaaki, Meshari Alazmi, Baraa AlhajHussein, Muhammad Yaseen, Hosam M. Zowawi, Majed F. Alghoribi, Abdulhakeem O. Althaqafi, Abdulfattah Al-Amri, Danesh Moradigaravand, Arnab Pain
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Abstract

Klebsiella pneumoniae is a major bacterial and opportunistic human pathogen, increasingly recognized as a healthcare burden globally. The convergence of resistance and virulence in K. pneumoniae strains has led to the formation of hypervirulent and multidrug-resistant strains with dual risk, limiting treatment options. K. pneumoniae clones are known to emerge locally and spread globally. Therefore, an understanding of the dynamics and evolution of the emerging strains in hospitals is warranted to prevent future outbreaks. In this study, we conducted an in-depth genomic analysis on a large-scale collection of 328 multidrug-resistant (MDR) K. pneumoniae strains recovered from 239 patients from a single major hospital in the western coastal city of Jeddah in Saudi Arabia from 2014 through 2022. We employed a broad range of phylogenetic and phylodynamic methods to understand the evolution of the predominant clones on epidemiological time scales, virulence and resistance determinants, and their dynamics. We also integrated the genomic data with detailed electronic health record (EHR) data for the patients to understand the clinical implications of the resistance and virulence of different strains. We discovered a diverse population underlying the infections, with most strains belonging to Clonal Complex 14 (CC14) exhibiting dominance. Specifically, we observed the emergence and continuous expansion of strains belonging to the dominant ST2096 in the CC14 clade across hospital wards in recent years. These strains acquired resistance mutations against colistin and extended spectrum β-lactamase (ESBL) and carbapenemase genes, namely blaOXA-48 and blaOXA-232, located on three distinct plasmids, on epidemiological time scales. Strains of ST2096 exhibited a high virulence level with the presence of the siderophore aerobactin (iuc) locus situated on the same mosaic plasmid as the ESBL gene. Integration of ST2096 with EHR data confirmed the significant link between colonization by ST2096 and the diagnosis of sepsis and elevated in-hospital mortality (p-value < 0.05). Overall, these results demonstrate the clinical significance of ST2096 clones and illustrate the rapid evolution of an emerging hypervirulent and MDR K. pneumoniae in a clinical setting.
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一家三级医院 8 年间出现高耐药性和高病毒性肺炎克雷伯菌 CC14 克隆
肺炎克雷伯氏菌是一种主要的细菌性和机会性人类病原体,日益成为全球公认的医疗负担。肺炎克雷伯菌株的耐药性和毒力趋于一致,形成了具有双重风险的高病毒性和多重耐药菌株,限制了治疗方案。众所周知,肺炎双球菌克隆会在局部地区出现,并在全球范围内传播。因此,有必要了解医院中新出现菌株的动态和演化,以防止未来的疫情爆发。在本研究中,我们对大规模收集的 328 株耐多药(MDR)肺炎克雷伯菌株进行了深入的基因组分析,这些菌株从 2014 年到 2022 年从沙特阿拉伯西部沿海城市吉达的一家大型医院的 239 名患者中回收。我们采用了多种系统发育和系统动力学方法来了解主要克隆在流行病学时间尺度上的演化、毒力和耐药性决定因素及其动态。我们还将基因组数据与患者的详细电子健康记录(EHR)数据相结合,以了解不同菌株的耐药性和毒力对临床的影响。我们发现,感染的基本菌群多种多样,属于克隆复合体 14(CC14)的大多数菌株表现出优势。具体来说,我们观察到近年来在医院病房中出现了属于 CC14 支系中占优势的 ST2096 菌株,并不断扩大。这些菌株在流行病学时间尺度上获得了对可乐定、广谱β-内酰胺酶(ESBL)和碳青霉烯酶基因(即位于三个不同质粒上的 blaOXA-48 和 blaOXA-232)的耐药性突变。ST2096 菌株表现出较高的毒力水平,其嗜苷杆菌素(iuc)基因座与 ESBL 基因位于同一嵌合质粒上。将 ST2096 与 EHR 数据整合后证实,ST2096 的定植与脓毒症诊断和院内死亡率升高之间存在显著联系(p 值 < 0.05)。总之,这些结果证明了 ST2096 克隆的临床意义,并说明了在临床环境中新出现的高病毒性和 MDR 肺炎 K.菌的快速进化。
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来源期刊
Genome Medicine
Genome Medicine GENETICS & HEREDITY-
CiteScore
20.80
自引率
0.80%
发文量
128
审稿时长
6-12 weeks
期刊介绍: Genome Medicine is an open access journal that publishes outstanding research applying genetics, genomics, and multi-omics to understand, diagnose, and treat disease. Bridging basic science and clinical research, it covers areas such as cancer genomics, immuno-oncology, immunogenomics, infectious disease, microbiome, neurogenomics, systems medicine, clinical genomics, gene therapies, precision medicine, and clinical trials. The journal publishes original research, methods, software, and reviews to serve authors and promote broad interest and importance in the field.
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