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新型序列类型碳青霉烯耐药超级毒力 ST6417 的出现,其携带的 lncX3 质粒。

Emergence of a novel sequence type carbapenem-resistant hypervirulent ST6417 harboring on the lncX3 plasmid.

机构信息

Clinical Laboratory, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

出版信息

Microbiol Spectr. 2024 Oct 3;12(10):e0098424. doi: 10.1128/spectrum.00984-24. Epub 2024 Aug 20.

DOI:10.1128/spectrum.00984-24
PMID:39162259
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11448260/
Abstract

UNLABELLED

Carbapenem-resistant hypervirulent (CR-hvKP) is a significant pathogen causing major public health problems worldwide. This study characterized a novel sequence type 6417 (ST6471) CR-hvKP strain recovered from the blood of a male patient with septicemia. Strain CR2021 is not susceptible to carbapenems, cephalosporin, sulfonamides, quinolones, or levofloxacin and is susceptible to amikacin and tigecycline. Molecular typing indicated that ST6417 is derived from the most dominant hypervirulent (hvKP) clone in China, ST23, with a single-locus variation in . The genomic characterization of CR2021, which contains three plasmids, was performed through whole-genome sequencing. The plasmid pCR2021_IncFII contains 12 antibiotic resistance genes [, , , , , , , , , , , ], all of which are associated with genetic elements. The plasmid pCR2021_IncFIB carries crucial virulence-related genes, while the plasmid pCR2021_IncX3 only harbors the resistance gene and exhibits 99% similarity with two other -carrying IncX3 plasmids (pSHX180-NDM5, pNDM-K725), with coverage of 87% and 100%, respectively. The genetic region contains an additional IS26-Tn3 genetic module. Serum killing and anti-human neutrophil phagocytosis tests indicated that CR2021 exhibits high virulence, which was further confirmed in a larvae infection model. CR-hvKP is becoming more prevalent in China; however, the majority have evolved from the multidrug resistance clone ST11 and its variants by acquiring virulence factors. Conversely, CR-hvKP derived from hvKP, such as the clone ST23, remains relatively rare. Therefore, the discovery of ST6417 underscores the need for further research into the genetic characteristics and evolution of bacteria.

IMPORTANCE

ST11 and its variants, which often exhibit drug resistance, represent popular clones of carbapenem-resistant hypervirulent (CR-hvKP) in China, often leading to high morbidity and mortality rates owing to their high virulence and robust drug resistance. Conversely, CR-hvKP, originating from the high-virulence sequence type ST23, remains rarely reported. In this study, we identified a novel ST6417 CR-hvKP strain derived from ST23, carrying on an IncX3 plasmid conferring resistance to carbapenems. In addition, we elucidate its virulence, resistance to drugs, and genetic characteristics. The discovery of ST6417 highlights the diverse pathways in the evolution of CR-hvKP, warranting increased attention.

摘要

未加标签

耐碳青霉烯类超毒力 (CR-hvKP)是一种重要的病原体,在全球范围内造成重大公共卫生问题。本研究从一名败血症男性患者的血液中分离出一种新型序列类型 6417(ST6471)CR-hvKP 菌株。菌株 CR2021 对碳青霉烯类、头孢菌素类、磺胺类、喹诺酮类和左氧氟沙星均不敏感,仅对阿米卡星和替加环素敏感。分子分型表明,ST6417 源自中国最主要的超毒力 (hvKP)克隆株 ST23,在 中有一个单一位点变异。通过全基因组测序对含有三个质粒的 CR2021 的基因组特征进行了研究。质粒 pCR2021_IncFII 包含 12 个抗生素耐药基因 [ 、 、 、 、 、 、 、 、 、 、 ],所有这些基因都与遗传元件有关。质粒 pCR2021_IncFIB 携带关键的毒力相关基因,而质粒 pCR2021_IncX3 仅携带 耐药基因,与两个其他携带 IncX3 的质粒(pSHX180-NDM5、pNDM-K725)具有 99%的相似性,覆盖度分别为 87%和 100%。 基因区域包含一个额外的 IS26-Tn3 遗传模块。血清杀伤和抗人中性粒细胞吞噬试验表明,CR2021 具有高毒力,这在 幼虫感染模型中得到了进一步证实。耐碳青霉烯类超毒力 (CR-hvKP)在中国越来越普遍;然而,大多数是通过获得毒力因子从多药耐药克隆株 ST11 及其变体进化而来。相比之下,源自 hvKP 的 CR-hvKP,如克隆株 ST23,仍然相对较少。因此,ST6417 的发现凸显了进一步研究细菌遗传特征和进化的必要性。

重要性

中国流行的耐碳青霉烯类超毒力 (CR-hvKP)克隆株往往是 ST11 及其变体,它们通常具有耐药性,由于其高毒力和强大的耐药性,往往导致高发病率和死亡率。相比之下,源自高毒力序列类型 ST23 的 CR-hvKP 则很少报道。在本研究中,我们鉴定了一种新型 ST6417 CR-hvKP 菌株,源自 ST23,携带 IncX3 质粒,赋予其对碳青霉烯类药物的耐药性。此外,我们阐明了其毒力、耐药性和遗传特征。ST6417 的发现突显了 CR-hvKP 进化的多种途径,值得进一步关注。

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