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耐碳青霉烯鲍曼不动杆菌临床分离株的抗菌药物耐药性、毒力特征及系统发育基因组学的遗传基础

Genetic basis of antimicrobial resistance, virulence features and phylogenomics of carbapenem-resistant Acinetobacter baumannii clinical isolates.

作者信息

Lukovic Bojana, Kabic Jovana, Dragicevic Milan, Kuljanin Sonja, Dimkic Ivica, Jovcic Branko, Gajic Ina

机构信息

College of Health Sciences, Academy of Applied Studies Belgrade, Cara Dusana 254, Belgrade, 11080, Serbia.

Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.

出版信息

Infection. 2025 Feb;53(1):39-50. doi: 10.1007/s15010-024-02316-8. Epub 2024 Jun 10.

DOI:10.1007/s15010-024-02316-8
PMID:38856809
Abstract

PURPOSE

The worldwide emergence and clonal spread of carbapenem-resistant Acinetobacter baumannii (CRAB) is of great concern. In the present study, we determined the mechanisms of antimicrobial resistance, virulence gene repertoire and genomic relatedness of CRAB isolates circulating in Serbian hospitals.

METHODS

CRAB isolates were analyzed using whole-genome sequencing (WGS) for the presence of antimicrobial resistance-encoding genes, virulence factors-encoding genes, mobile genetic elements and genomic relatedness. Antimicrobial susceptibility testing was done by disk diffusion and broth microdilution methods.

RESULTS

Eleven isolates exhibited an MDR resistance phenotype, while four of them were XDR. MIC for meropenem and imipenem were > 64 µg/mL and 32 µg/mL, respectively. While all CRABs harbored bla variant of bla gene, those assigned to ST2, ST636 and ST492 had blabla and bla variants, respectively. The following acquired carbapenemases-encoding genes were found: bla (n = 12), bla (n = 3), and bla(n = 5), and were mapped to defined mobile genetic elements. MLST analysis assigned the analyzed CRAB isolates to three Pasteur sequence types (STs): ST2, ST492, and ST636. The Majority of strains belonged to International Clone II (ICII) and carried tested virulence-related genes liable for adherence, biofilm formation, iron uptake, heme biosynthesis, zinc utilization, serum resistance, stress adaptation, intracellular survival and toxin activity.

CONCLUSION

WGS elucidated the resistance and virulence profiles of CRABs isolated from clinical samples in Serbian hospitals and genomic relatedness of CRAB isolates from Serbia and globally distributed CRABs.

摘要

目的

耐碳青霉烯类鲍曼不动杆菌(CRAB)在全球范围内的出现和克隆传播令人高度关注。在本研究中,我们确定了塞尔维亚医院中流行的CRAB分离株的耐药机制、毒力基因库和基因组相关性。

方法

使用全基因组测序(WGS)分析CRAB分离株中抗菌耐药编码基因、毒力因子编码基因、移动遗传元件和基因组相关性的存在情况。通过纸片扩散法和肉汤微量稀释法进行药敏试验。

结果

11株分离株表现出多重耐药(MDR)耐药表型,其中4株为广泛耐药(XDR)。美罗培南和亚胺培南的最低抑菌浓度(MIC)分别>64μg/mL和32μg/mL。虽然所有CRAB均携带bla基因的bla变体,但分别属于序列型2(ST2)、ST636和ST492的菌株具有blabla和bla变体。发现了以下获得性碳青霉烯酶编码基因:bla(n = 12)、bla(n = 3)和bla(n = 5),并将其定位到特定的移动遗传元件上。多位点序列分型(MLST)分析将所分析的CRAB分离株归为三种巴斯德序列型(STs):ST2、ST492和ST636。大多数菌株属于国际克隆II(ICII),并携带与毒力相关的测试基因,这些基因与黏附、生物膜形成、铁摄取、血红素生物合成、锌利用、血清抗性、应激适应、细胞内存活和毒素活性有关。

结论

全基因组测序阐明了塞尔维亚医院临床样本中分离出的CRAB的耐药性和毒力谱,以及塞尔维亚CRAB分离株与全球分布的CRAB的基因组相关性。

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