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黎巴嫩耐万古霉素的关键基因组见解。

Critical genomic insights into vancomycin-resistant in Lebanon.

作者信息

Osman Marwan, Yassine Iman, Hassan Jouman, Ericson Jessica E, Schiff Steven J, Ghorbani Tajani Anahita, Bisha Bledar, Hamze Monzer, Kassem Issmat I

机构信息

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut, USA.

Laboratoire Microbiologie, Santé et Environnement (LMSE), Doctoral School of Sciences and Technology, Faculty of Public Health, Lebanese University, Tripoli, Lebanon.

出版信息

Microbiol Spectr. 2025 Aug 5:e0017125. doi: 10.1128/spectrum.00171-25.

DOI:10.1128/spectrum.00171-25
PMID:40762484
Abstract

UNLABELLED

Vancomycin-resistant (VRE) poses a global public health threat, with particularly severe ramifications in low-resource settings. While is commonly a commensal organism in the human gut, the acquisition of vancomycin resistance has contributed to the emergence of VRE as a major cause of hospital-acquired infections, especially in vulnerable populations. This study investigates the genetic characteristics of VRE isolated from hospitalized patients in Lebanon, focusing on antimicrobial resistance (AMR) phenotypes and the underlying resistome. We collected VRE isolates from patients at the time of admission or during routine screenings for multidrug-resistant pathogens. The isolates were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and screened for antimicrobial susceptibility using the disk diffusion and E-test methods. Whole genome sequencing was conducted using Illumina technology, and bioinformatics analyses were carried out to identify the resistome, sequence types, plasmid types, and virulence genes. Additionally, we analyzed previously GenBank-deposited VRE genomes from Lebanon to assess genetic relationships. Our VRE isolates carried multiple acquired AMR genes and chromosomal mutations, exhibiting resistance to vancomycin, telavancin, ampicillin, erythromycin, norfloxacin, levofloxacin, and nitrofurantoin. The isolates belonged to three subtypes: ST203 (67%), ST612 (22%), and a novel ST2711 (11%), all of which belonged to CC17, a globally prevalent hospital-associated lineage known for high levels of AMR and hospital outbreaks. Core-genome single nucleotide variants (SNVs) phylogenetic analysis revealed that the ST203 isolates clustered with the previously GenBank-deposited ST203 Lebanese genomes. Taken together, these findings highlight the growing VRE burden in low-resource countries, emphasizing the need for enhanced surveillance and alternative treatment strategies.

IMPORTANCE

The healthcare system in Lebanon faces substantial challenges due to ongoing economic instability and limited resources, creating a conducive environment for the spread of antimicrobial resistance. Vancomycin-resistant (VRE) represents a growing public health threat, yet studies addressing its genetics in Lebanon are scarce. This study provided critical insights into the genomic features of VRE in clinical settings, highlighting the potential clonal dissemination of multidrug-resistant isolates carrying the operon and belonging to CC17, a globally prevalent, hospital-associated lineage. Resistance to novel antimicrobials, such as telavancin, dalbavancin, and eravacycline, is alarming and necessitates immediate action to preserve these critical last-resort interventions. Notably, the identification of clonal spread and a novel sequence type (ST2711) within Lebanese hospitals, alongside resistance to last-resort antimicrobials, highlights the dynamic evolution of VRE and the urgent need to strengthen antimicrobial stewardship programs in Lebanon and beyond. Addressing this challenge requires integrated One Health strategies.

摘要

未标注

耐万古霉素肠球菌(VRE)对全球公共卫生构成威胁,在资源匮乏地区的影响尤为严重。虽然肠球菌通常是人类肠道中的共生菌,但获得万古霉素耐药性促使VRE成为医院获得性感染的主要原因,尤其是在弱势群体中。本研究调查了从黎巴嫩住院患者中分离出的VRE的遗传特征,重点关注抗菌药物耐药性(AMR)表型和潜在的耐药基因组。我们在患者入院时或对多重耐药病原体进行常规筛查期间收集VRE分离株。使用基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF MS)鉴定分离株,并使用纸片扩散法和E-test法筛查抗菌药物敏感性。使用Illumina技术进行全基因组测序,并进行生物信息学分析以鉴定耐药基因组、序列类型、质粒类型和毒力基因。此外,我们分析了之前存放在GenBank中的黎巴嫩VRE基因组,以评估遗传关系。我们的VRE分离株携带多个获得性AMR基因和染色体突变,对万古霉素、替考拉宁、氨苄西林、红霉素、诺氟沙星、左氧氟沙星和呋喃妥因表现出耐药性。分离株属于三个亚型:ST203(67%)、ST612(22%)和一个新的ST2711(11%),它们都属于CC17,这是一个全球流行的与医院相关的谱系,以高水平的AMR和医院暴发而闻名。核心基因组单核苷酸变异(SNV)系统发育分析表明,ST203分离株与之前存放在GenBank中的黎巴嫩ST203基因组聚类。综上所述,这些发现凸显了资源匮乏国家中VRE负担的不断增加,强调了加强监测和替代治疗策略的必要性。

重要性

由于持续的经济不稳定和资源有限,黎巴嫩的医疗系统面临重大挑战,为抗菌药物耐药性的传播创造了有利环境。耐万古霉素肠球菌(VRE)对公共卫生的威胁日益增加,但在黎巴嫩针对其遗传学的研究却很少。本研究为临床环境中VRE的基因组特征提供了关键见解,突出了携带操纵子且属于CC17(一个全球流行的与医院相关的谱系)的多重耐药分离株的潜在克隆传播。对新型抗菌药物如替考拉宁、达巴万星和依拉环素的耐药性令人担忧,需要立即采取行动以保留这些关键的最后手段干预措施。值得注意的是,在黎巴嫩医院内鉴定出克隆传播和一种新的序列类型(ST2711),以及对最后手段抗菌药物的耐药性,凸显了VRE的动态演变以及在黎巴嫩及其他地区加强抗菌药物管理计划的迫切需求。应对这一挑战需要综合的“同一健康”策略。

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