The convergence of hypervirulence and carbapenem resistance in the bacterial pathogen Klebsiella pneumoniae represents a critical global health concern. Hypervirulent K. pneumoniae (hvKp) strains, frequently from sequence type 23 (ST23) and having a K1 capsule, have been associated with severe community-acquired invasive infections. Although hvKp were initially restricted to Southeast Asia and primarily antibiotic-sensitive, carbapenem-resistant hvKp infections are reported worldwide. Here, within the carbapenemase production Enterobacterales surveillance system headed by the Chilean Public Health Institute, we describe the isolation in Chile of a high-risk ST23 dual-carbapenemase-producing hvKp strain, which carbapenemase genes are encoded in a single conjugative plasmid. Phenotypic and molecular tests of this strain revealed an extensive resistance to at least 15 antibiotic classes and the production of KPC-2 and VIM-1 carbapenemases. Unexpectedly, this isolate lacked hypermucoviscosity, challenging this commonly used hvKp identification criteria. Complete genome sequencing and analysis confirmed the K1 capsular type, the KpVP-1 virulence plasmid, and the GIE492 and ICEKp10 genomic islands carrying virulence factors strongly associated with hvKp. Although this isolate belonged to the globally disseminated hvKp clonal group CG23-I, it is unique, as it formed a clade apart from a previously reported Chilean ST23 hvKp isolate and acquired an IncN KPC-2 plasmid highly disseminated in South America (absent in other hvKp genomes), but now including a class-I integron carrying blaVIM−1 and other resistance genes. Notably, this isolate was able to conjugate the double carbapenemase plasmid to an E. coli recipient, conferring resistance to 1st -5th generation cephalosporins (including combinations with beta-lactamase inhibitors), penicillins, monobactams, and carbapenems. We reported the isolation in Chile of high-risk carbapenem-resistant hvKp carrying a highly transmissible conjugative plasmid encoding KPC-2 and VIM-1 carbapenemases, conferring resistance to most beta-lactams. Furthermore, the lack of hypermucoviscosity argues against this trait as a reliable hvKp marker. These findings highlight the rapid evolution towards multi-drug resistance of hvKp in Chile and globally, as well as the importance of conjugative plasmids and other mobile genetic elements in this convergence. In this regard, genomic approaches provide valuable support to monitor and obtain essential information on these priority pathogens and mobile elements.

中文翻译：

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智利具有高传染性双碳青霉烯酶质粒的碳青霉烯类耐药高毒力 ST23 肺炎克雷伯菌

细菌病原体肺炎克雷伯菌的高毒力和碳青霉烯类耐药性的结合代表了一个严重的全球健康问题。高毒力肺炎克雷伯菌 (hvKp) 菌株通常来自序列类型 23 (ST23) 并具有 K1 荚膜，与严重的社区获得性侵袭性感染有关。尽管 hvKp 最初仅限于东南亚且主要对抗生素敏感，但全球范围内都有碳青霉烯类耐药性 hvKp 感染的报道。在此，在智利公共卫生研究所领导的碳青霉烯酶生产肠杆菌监测系统内，我们描述了在智利分离出的高风险 ST23 双碳青霉烯酶生产 hvKp 菌株，该菌株的碳青霉烯酶基因编码在单个接合质粒中。该菌株的表型和分子测试揭示了对至少 15 种抗生素的广泛耐药性，并产生 KPC-2 和 VIM-1 碳青霉烯酶。出乎意料的是，该分离株缺乏高粘膜粘度，对常用的 hvKp 鉴定标准提出了挑战。完整的基因组测序和分析证实了 K1 荚膜类型、KpVP-1 毒力质粒以及携带与 hvKp 密切相关毒力因子的 GIE492 和 ICEKp10 基因组岛。尽管该分离株属于全球传播的 hvKp 克隆群 CG23-I，但它是独特的，因为它与先前报道的智利 ST23 hvKp 分离株形成了一个分支，并获得了在南美洲高度传播的 IncN KPC-2 质粒（在其他地区不存在）。 hvKp 基因组），但现在包括携带 blaVIM−1 和其他抗性基因的 I 类整合子。值得注意的是，该分离株能够将双碳青霉烯酶质粒与大肠杆菌受体结合，赋予对第一代-第五代头孢菌素（包括与β-内酰胺酶抑制剂的组合）、青霉素、单环内酰胺和碳青霉烯类的抗性。我们报道了在智利分离出的高风险碳青霉烯类抗性 hvKp，其携带编码 KPC-2 和 VIM-1 碳青霉烯酶的高传播性接合质粒，赋予对大多数 β-内酰胺类的抗性。此外，缺乏高粘膜粘稠性不利于将此性状作为可靠的 hvKp 标记。这些发现强调了 hvKp 在智利和全球范围内向多重耐药性的快速进化，以及接合质粒和其他移动遗传元件在这种融合中的重要性。在这方面，基因组方法为监测和获取有关这些优先病原体和移动元件的基本信息提供了宝贵的支持。