16S rRNA 甲基转移酶产生肠杆菌的基因组特征研究发现保加利亚一家癌症医院出现了携带 rmtF、rmtB、blaNDM-5、blaOXA-232 和 blaSFO-1 基因的肺炎克雷伯菌 ST6260。

IF 4.3 2区医学 Q1 INFECTIOUS DISEASES

Antibiotics-Basel Pub Date : 2024-10-10 DOI:10.3390/antibiotics13100950

Stefana Sabtcheva, Ivan Stoikov, Sylvia Georgieva, Deyan Donchev, Yordan Hodzhev, Elina Dobreva, Iva Christova, Ivan N Ivanov

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引用次数: 0

摘要

背景：获得性 16S rRNA 甲基转移酶（16S-RMTases）可产生对氨基糖苷类药物的高水平耐药性，并且通常与 β-内酰胺类和喹诺酮类药物的耐药性决定因素有关。方法：利用 PCR、全基因组测序和连接实验，我们对 2006 年至 2023 年间收集的产 16S-RMTase 肠杆菌进行了一项回顾性基因组监测研究，以探索甲基转移酶和相关抗生素耐药基因的传播动态。研究结果在 10731 个连续分离株中，来自 13 个物种的 150 个（1.4%）携带 armA（92.7%）、rmtB（4.7%）和 rmtF + rmtB（2.7%）甲基转移酶基因。在这些分离物中还检测到了广谱β-内酰胺酶（blaCTX-M-3/15、blaSHV-12、blaSFO-1）、碳青霉烯酶（blaNDM-1/5、blaVIM-1/4/86、blaOXA-48）、获得性AmpC（blaCMY-2/4/99、blaDHA-1、blaAAC-1）和质粒介导的喹诺酮耐药性（qnrB、qnrS、aac(6')-Ib-cr）基因的共存。甲基转移酶基因由不同的质粒（IncL/M、IncA/C、IncR、IncFIB 和 IncFII）携带，表明其来源和获得途径各不相同。armA与blaCTX-M-3/15、blaNDM-1、blaVIM-4/86、blaOXA-48、blaCMY-4、aac(6')-Ib-cr、qnrB和qnrS共转，而rmtF1与blaSFO-1共转，突出了这些质粒的多重耐药性。ST6260肺炎克雷伯菌分离物的长读测序发现了一种新的耐药性关联，rmtB1和blaNDM-5在染色体上，blaOXA-232在共轭ColKP3质粒上，rmtF1和blaSFO-1在自传播的IncFIB和IncFII质粒上。结论携带甲基转移酶基因的质粒具有遗传可塑性，这表明它们有可能获得更多的抗性基因，从而使产生 16S-RMTase 的肠杆菌成为一种持久的公共卫生威胁。

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Genomic Characterization of 16S rRNA Methyltransferase-Producing Enterobacterales Reveals the Emergence of Klebsiella pneumoniae ST6260 Harboring rmtF, rmtB, bla_NDM-5, bla_OXA-232 and bla_SFO-1 Genes in a Cancer Hospital in Bulgaria.

Background: Acquired 16S rRNA methyltransferases (16S-RMTases) confer high-level resistance to aminoglycosides and are often associated with β-lactam and quinolone resistance determinants. Methods: Using PCR, whole-genome sequencing and conjugation experiments, we conducted a retrospective genomic surveillance study of 16S-RMTase-producing Enterobacterales, collected between 2006 and 2023, to explore transmission dynamics of methyltransferase and associated antibiotic resistance genes. Results: Among the 10,731 consecutive isolates, 150 (1.4%) from 13 species carried armA (92.7%), rmtB (4.7%), and rmtF + rmtB (2.7%) methyltransferase genes. The coexistence of extended-spectrum β-lactamase (bla_CTX-M-3/15, bla_SHV-12, bla_SFO-1), carbapenemase (bla_NDM-1/5, bla_VIM-1/4/86, bla_OXA-48), acquired AmpC (bla_CMY-2/4/99, bla_DHA-1, bla_AAC-1), and plasmid-mediated quinolone resistance (qnrB, qnrS, aac(6')-Ib-cr) genes within these isolates was also detected. Methyltransferase genes were carried by different plasmids (IncL/M, IncA/C, IncR, IncFIB, and IncFII), suggesting diverse origins and sources of acquisition. armA was co-transferred with bla_CTX-M-3/15, bla_NDM-1, bla_VIM-4/86, bla_OXA-48, bla_CMY-4, aac(6')-Ib-cr, qnrB, and qnrS, while rmtF1 was co-transferred with bla_SFO-1, highlighting the multidrug-resistant nature of these plasmids. Long-read sequencing of ST6260 K. pneumoniae isolates revealed a novel resistance association, with rmtB1 and bla_NDM-5 on the chromosome, bla_OXA-232 on a conjugative ColKP3 plasmid, and rmtF1 with bla_SFO-1 on self-transmissible IncFIB and IncFII plasmids. Conclusions: The genetic plasticity of plasmids carrying methyltransferase genes suggests their potential to acquire additional resistance genes, turning 16S-RMTase-producing Enterobacterales into a persistent public health threat.

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来源期刊

Antibiotics-Basel Pharmacology, Toxicology and Pharmaceutics-General Pharmacology, Toxicology and Pharmaceutics

CiteScore

7.30

自引率

14.60%

发文量

1547

审稿时长

11 weeks

期刊介绍： Antibiotics (ISSN 2079-6382) is an open access, peer reviewed journal on all aspects of antibiotics. Antibiotics is a multi-disciplinary journal encompassing the general fields of biochemistry, chemistry, genetics, microbiology and pharmacology. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. Therefore, there is no restriction on the length of papers.