Phenotypic and genomic characterization of ST11-K1 CR-hvKP with highly homologous bla_KPC-2-bearing plasmids in China.

IF 5 2区生物学 Q1 MICROBIOLOGY

mSystems Pub Date : 2024-11-18 DOI:10.1128/msystems.01101-24

Yu-Ling Han, Hua Wang, Hong-Zhe Zhu, Ying-Ying Lv, Wen Zhao, Yan-Yan Wang, Jian-Xun Wen, Zhi-De Hu, Jun-Rui Wang, Wen-Qi Zheng

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引用次数: 0

Abstract

Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) strains present a significant global public health threat due to their high mortality rates. This study investigated the genomic characteristics of seven ST11-K1 CR-hvKP isolates harboring highly homologous KPC-2-encoding multidrug-resistance plasmids. The strains were isolated from a Chinese tertiary hospital between 2017 and 2020. Whole-genome sequencing and bioinformatic analysis revealed various antibiotic resistance genes (ARGs) and virulence determinants. The bla_KPC-2-bearing plasmids that contain multiple antibiotic-resistance genes were also identified in these strains. ISfinder and Orifinder were applied to identify insertion sequences (IS) and conjugation-related factors among these bla_KPC-2-bearing plasmids. The bla_KPC-2 was highly consistent in seven bla_KPC-2-bearing plasmids (ISKpn6-bla_KPC-2-ISKpn27-ISYps3-IS26). In addition, we found a region composed of ISIR, Tn5393, and IS26. It was located upstream of the bla_CTX-M-15 gene and presented in six bla_KPC-2-bearing plasmids, with pCR-hvKP221-KPC-P3 as an exception. Conjugation experiments demonstrated the horizontal transfer of resistance plasmids pCR-hvKP128-KPC-P1 and pCR-hvKP132-KPC-P1 across species. Notably, pLVPK-like virulence plasmids carrying virulence gene clusters pCR-hvKP173-Vir-P1, and pCR-hvKP221-Vir-P1 were also detected. A fusional plasmid pCR-hvKP221-Vir-P2, which carries virulence gene clusters and ARGs, was also identified. Five CR-hvKP strains displayed enhanced biofilm formation and high virulence in vivo infection models. Phylogenetic and single nucleotide polymorphism (SNP) analyses indicated a close genetic relationship among the isolates, suggesting a subclade. These findings highlight the complex genetic profiles and potential transmission mechanisms of CR-hvKP strains.

Importance: We reported seven CR-hvKP strains all carried a highly homologous bla_KPC-2 integrated IncFⅡ-resistant plasmid, and two strains harbored virulence plasmids. Conjugation experiments confirmed the transferability of these plasmids, indicating a potential for resistance spread. Phylogenetic analysis clarified the relationship among the CR-hvKP isolates. This study provides insights into the phenotypic and genomic characteristics of seven ST11-K1 CR-hvKP strains. The high prevalence and potential for local outbreaks emphasize the need for effective control measures.

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中国带有高度同源 blaKPC-2 质粒的 ST11-K1 CR-hvKP 的表型和基因组特征。

耐碳青霉烯类药物的高病毒性肺炎克雷伯氏菌（CR-hvKP）菌株因其高死亡率而对全球公共卫生构成重大威胁。本研究调查了 7 株 ST11-K1 CR-hvKP 分离株的基因组特征，这些分离株携带高度同源的 KPC-2 编码多重耐药质粒。这些菌株于 2017 年至 2020 年期间从一家中国三级医院分离出来。全基因组测序和生物信息学分析揭示了各种抗生素耐药基因（ARGs）和毒力决定因子。在这些菌株中还发现了含有多种抗生素耐药基因的 blaKPC-2 质粒。应用 ISfinder 和 Orifinder 在这些含有 blaKPC-2 的质粒中鉴定插入序列（IS）和共轭相关因子。在七个含有 blaKPC-2 的质粒（ISKpn6-blaKPC-2-ISKpn27-ISYps3-IS26）中，blaKPC-2 高度一致。此外，我们还发现了一个由 ISIR、Tn5393 和 IS26 组成的区域。它位于 blaCTX-M-15 基因的上游，出现在六个含有 blaKPC-2 的质粒中，pCR-hvKP221-KPC-P3 是个例外。共轭实验证明了抗性质粒 pCR-hvKP128-KPC-P1 和 pCR-hvKP132-KPC-P1 的跨物种水平转移。值得注意的是，还检测到了携带毒力基因簇 pCR-hvKP173-Vir-P1 和 pCR-hvKP221-Vir-P1 的类 pLVPK 毒力质粒。此外，还发现了携带毒力基因簇和 ARG 的融合质粒 pCR-hvKP221-Vir-P2。五株 CR-hvKP 菌株在体内感染模型中显示出更强的生物膜形成能力和高毒力。系统发育和单核苷酸多态性（SNP）分析表明，这些分离株之间存在密切的遗传关系，表明存在一个亚支系。这些发现凸显了CR-hvKP菌株复杂的遗传特征和潜在的传播机制：我们报告的七株CR-hvKP菌株均携带高度同源的blaKPC-2整合IncFⅡ抗性质粒，其中两株携带毒力质粒。共轭实验证实了这些质粒的可转移性，表明了抗药性传播的可能性。系统发育分析明确了 CR-hvKP 分离物之间的关系。这项研究深入揭示了七株 ST11-K1 CR-hvKP 菌株的表型和基因组特征。高流行率和局部爆发的可能性强调了采取有效控制措施的必要性。

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来源期刊

mSystems Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

10.50

自引率

3.10%

发文量

308

审稿时长

13 weeks

期刊介绍： mSystems™ will publish preeminent work that stems from applying technologies for high-throughput analyses to achieve insights into the metabolic and regulatory systems at the scale of both the single cell and microbial communities. The scope of mSystems™ encompasses all important biological and biochemical findings drawn from analyses of large data sets, as well as new computational approaches for deriving these insights. mSystems™ will welcome submissions from researchers who focus on the microbiome, genomics, metagenomics, transcriptomics, metabolomics, proteomics, glycomics, bioinformatics, and computational microbiology. mSystems™ will provide streamlined decisions, while carrying on ASM''s tradition of rigorous peer review.