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对从越南胃病患者中分离出的新型序列类型的多重耐药幽门螺杆菌菌株的毒力、生物膜形成和抗菌耐药性的基因组学见解。

Genomic insights into virulence, biofilm formation, and antimicrobial resistance of multidrug-resistant Helicobacter pylori strains of novel sequence types isolated from Vietnamese patients with gastric diseases.

作者信息

Bui Thanh Thuyet, Tran Thi Thanh Tam, Nguyen Thai Son, Le Thi Thu Hang, Nguyen Cam Linh, Pham Hoang Nam, Bañuls Anne-Laure, Le Huu Song, Le Huu Phuong Anh, Bui Thi Tho, Bui Tien Sy, Phan Quoc Hoan, Tran Thi Huyen Trang, Nguyen Quang Huy

机构信息

Department of Microbiology, 108 Military Central Hospital, Hanoi, Vietnam; Vietnamese-German Center for Medical Research (VG-CARE), 108 Military Central Hospital, Hanoi, Vietnam.

MICH Group, LMI DRISA, University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Vietnam.

出版信息

J Glob Antimicrob Resist. 2025 Jun;43:237-241. doi: 10.1016/j.jgar.2025.05.001. Epub 2025 May 8.

DOI:10.1016/j.jgar.2025.05.001
PMID:40345333
Abstract

Helicobacter pylori (H. pylori) is a clinically important pathogen associated with gastric diseases. Here, we characterized the genome of multidrug-resistant H. pylori strains of novel sequence types, which were recovered from Vietnamese patients with gastritis or a stomach ulcer. Phenotypic-antibiotic susceptibility testing was performed against amoxicillin, clarithromycin, metronidazol, tetracycline, and levofloxacin using an E-test. The whole genome sequence of three H. pylori strains was de novo assembled, followed by in silico analysis of multilocus sequence typing (MLST), core-genome based phylogeny, genetic determinants associated with virulence, biofilm formation, and antibiotic-resistance. The genome sequence of H. pylori strains exhibited a high similarity with the average nucleotide identity (ANI) values of 98.5% to 99.2%, carried 5 to 7 pathogenicity islands, and 3 to 6 mobilomes. The MLST profile of strains revealed novel sequence types ST4511, ST4512, and ST4513. Core-genome based phylogeny exhibited that the three H. pylori strains belong to the Asian genotype. These strains possessed 128 to 131 virulence genes, including toxin-encoding genes cagA and vacA. Double amoxicillin-resistant mutations on pbp1 and pbp2, or a mutation on pbp3, triple clarithromycin-resistant mutations on 23S rRNA gene and a levofloxacin-resistant mutation on gyrA were detected in antibiotic-resistant strains. Mutations on rdxA were detected in both metronidazole-resistant and -sensitive strains, whereas frxA mutations were detected in only one metronidazole-sensitive strain. Finally, a rifamycin-resistant mutation in rpoB was also detected. This study provides insights into the genome of multidrug-resistant H. pylori strains of a novel sequence type circulating in Vietnam for future investigations of its pathobiology and spread through human populations.

摘要

幽门螺杆菌(H. pylori)是一种与胃部疾病相关的具有临床重要性的病原体。在此,我们对从越南胃炎或胃溃疡患者中分离出的新型序列类型的多重耐药幽门螺杆菌菌株的基因组进行了特征分析。使用E-test对阿莫西林、克拉霉素、甲硝唑、四环素和左氧氟沙星进行了表型抗生素敏感性测试。对三株幽门螺杆菌菌株的全基因组序列进行了从头组装,随后对多位点序列分型(MLST)、基于核心基因组的系统发育、与毒力、生物膜形成和抗生素耐药性相关的遗传决定因素进行了计算机分析。幽门螺杆菌菌株的基因组序列显示出高度相似性,平均核苷酸同一性(ANI)值为98.5%至99.2%,携带5至7个致病岛和3至6个可移动遗传元件。菌株的MLST谱显示了新型序列类型ST4511、ST4512和ST4513。基于核心基因组的系统发育显示,这三株幽门螺杆菌菌株属于亚洲基因型。这些菌株拥有128至131个毒力基因,包括编码毒素的基因cagA和vacA。在耐药菌株中检测到pbp1和pbp2上的双阿莫西林耐药突变,或pbp3上的突变,23S rRNA基因上的三重克拉霉素耐药突变以及gyrA上的左氧氟沙星耐药突变。在甲硝唑耐药和敏感菌株中均检测到rdxA突变,而仅在一株甲硝唑敏感菌株中检测到frxA突变。最后,还检测到rpoB中的利福霉素耐药突变。本研究为越南流行的新型序列类型的多重耐药幽门螺杆菌菌株的基因组提供了见解,以便未来对其病理生物学和在人群中的传播进行研究。

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