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泰国广泛耐药鲍曼不动杆菌临床分离株的全基因组分析。

Whole Genome Analysis of Extensively Drug-Resistant Acinetobacter baumannii Clinical Isolates in Thailand.

机构信息

Faculty of Public Health, Kasetsart University, Chalermphrakiat Sakon Nakhon Province Campus, Sakon Nakhon, Thailand.

Japan-Thailand Research Collaboration Center for Infectious Diseases, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.

出版信息

Infect Disord Drug Targets. 2021;21(5):e270421188042. doi: 10.2174/1871526520999201116201911.

DOI:10.2174/1871526520999201116201911
PMID:33200701
Abstract

BACKGROUND

Acinetobacter baumannii is recognized as a majority opportunistic nosocomial pathogen causing hospital-acquired infection worldwide. The increasing prevalence of extensively drug-resistant Acinetobacter baumannii (XDRAB) has become a rising concern in healthcare facilities and has impeded public health due to limitation of therapeutic options and are associated with high morbidity and mortality as well as longer hospitalization. Whole-genome sequencing of highly multidrug resistant A. baumannii will increase the understanding of resistant mechanisms, the emergence of novel resistance, genetic relationships among the isolates, source tracking, and treatment decisions in selected patients.

OBJECTIVE

This study revealed the genomic analysis to explore blaOXA-23 harboring XDRAB isolates in Thailand.

METHODS

Whole-genome sequencing of the two XDRAB isolates was carried out on a HiSeq2000 Illumina platform and susceptibility on antimicrobials was conducted.

RESULTS

Both isolates revealed sequence types of international, clone II-carrying, multiple antimicrobial- resistant genes-ST195 and ST451. They were resistant to antimicrobial agents in all drug classes tested for Acinetobacter spp. They carried 18 antimicrobial-resistant genes comprising of 4 β-lactamase genes (blaOXA-23, blaOXA-66, blaTEM-1D, blaADC-25), 4 aminoglycoside-resistant genes (armA, aph(3')-Ia, aph(3")-Ib, aph(6)-Id), 3 macrolide-resistant genes (amvA, mphE, msrE), 1 sulfonamide- resistant gene (sul-2), 2 tetracycline-resistant genes (tetB, tetR), 1 resistant-nodulation-cell division (RND) antibiotic efflux pump gene cluster, 2 major facilitator superfamily (MFS) antibiotic efflux pump genes (abaF, abaQ), and 1 small multidrug-resistant (SMR) antibiotic efflux pump gene (abeS). Mutation of gyrA (S81L) occurred in both isolates.

CONCLUSION

Whole-genome sequencing revealed both blaOXA-23 harboring XDRAB isolates were clustered under international clone II with different STs and carrying multiple antimicrobial-resistant genes conferred their resistance to antimicrobial agents. Inactivation of antimicrobials and target modification by enzymes and pumping antibiotics by efflux pump are mainly resistance mechanism of the XDRAB in this study.

摘要

背景

鲍曼不动杆菌被认为是一种主要的机会性医院获得性病原体,在全球范围内引起医院感染。广泛耐药鲍曼不动杆菌(XDRAB)的患病率不断上升,已成为医疗机构的一个令人关注的问题,由于治疗选择有限,并且与高发病率和死亡率以及更长的住院时间有关,因此对公共卫生造成了影响。对高度多药耐药鲍曼不动杆菌进行全基因组测序将增加对耐药机制、新型耐药的出现、分离株之间的遗传关系、源追踪以及选定患者的治疗决策的了解。

目的

本研究揭示了基因组分析,以探讨泰国携带 blaOXA-23 的 XDRAB 分离株。

方法

对 2 株 XDRAB 分离株进行全基因组测序,在 HiSeq2000 Illumina 平台上进行,并对其对抗微生物药物的敏感性进行检测。

结果

两株分离株均显示国际流行的克隆 II 型,携带多种耐药基因的 ST195 和 ST451。它们对所有测试的用于鲍曼不动杆菌的药物类别均具有抗药性。它们携带 18 个抗生素耐药基因,包括 4 个β-内酰胺酶基因(blaOXA-23、blaOXA-66、blaTEM-1D、blaADC-25)、4 个氨基糖苷类耐药基因(armA、aph(3')-Ia、aph(3")-Ib、aph(6)-Id)、3 个大环内酯类耐药基因(amvA、mphE、msrE)、1 个磺胺类耐药基因(sul-2)、2 个四环素耐药基因(tetB、tetR)、1 个耐药-结节-分裂(RND)抗生素外排泵基因簇、2 个主要易化因子超家族(MFS)抗生素外排泵基因(abaF、abaQ)和 1 个小多药耐药(SMR)抗生素外排泵基因(abeS)。gyrA(S81L)突变发生在两株分离株中。

结论

全基因组测序显示,两株携带 blaOXA-23 的 XDRAB 分离株均属于国际克隆 II 型,具有不同的 ST 并携带多种抗生素耐药基因,使其对抗生素具有耐药性。在本研究中,抗生素的失活和靶标修饰主要通过酶和外排泵将抗生素泵出,这是 XDRAB 的主要耐药机制。

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