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与抗菌药物耐药性相关的基因组可塑性。

Genomic plasticity associated with antimicrobial resistance in .

机构信息

Molecular Genetics Laboratory, Centre for Human Microbial Ecology, Translational Health Science and Technology Institute, Faridabad 121001, India.

Regional Centre for Biotechnology, Faridabad 121001, India.

出版信息

Proc Natl Acad Sci U S A. 2019 Mar 26;116(13):6226-6231. doi: 10.1073/pnas.1900141116. Epub 2019 Mar 13.

Abstract

The Bay of Bengal is known as the epicenter for seeding several devastating cholera outbreaks across the globe. , the etiological agent of cholera, has extraordinary competency to acquire exogenous DNA by horizontal gene transfer (HGT) and adapt them into its genome for structuring metabolic processes, developing drug resistance, and colonizing the human intestine. Antimicrobial resistance (AMR) in has become a global concern. However, little is known about the identity of the resistance traits, source of AMR genes, acquisition process, and stability of the genetic elements linked with resistance genes in Here we present details of AMR profiles of 443 strains isolated from the stool samples of diarrheal patients from two regions of India. We sequenced the whole genome of multidrug-resistant (MDR) and extensively drug-resistant (XDR) to identify AMR genes and genomic elements that harbor the resistance traits. Our genomic findings were further confirmed by proteome analysis. We also engineered the genome of to monitor the importance of the autonomously replicating plasmid and core genome in the resistance profile. Our findings provided insights into the genomes of recent cholera isolates and identified several acquired traits including plasmids, transposons, integrative conjugative elements (ICEs), pathogenicity islands (PIs), prophages, and gene cassettes that confer fitness to the pathogen. The knowledge generated from this study would help in better understanding of evolution and management of cholera disease by providing clinical guidance on preferred treatment regimens.

摘要

孟加拉湾是全球多次破坏性霍乱疫情的震中,被称为爆发地。霍乱弧菌,作为霍乱的病原体,通过水平基因转移(HGT)具有非凡的能力来获取外源 DNA,并将其整合到基因组中,以构建代谢过程、产生耐药性以及定殖人类肠道。霍乱弧菌的抗生素耐药性(AMR)已成为全球关注的问题。然而,人们对耐药特征的身份、AMR 基因的来源、获取过程以及与耐药基因相关的遗传元件的稳定性知之甚少。在这里,我们介绍了从印度两个地区腹泻患者的粪便样本中分离的 443 株 的 AMR 图谱的详细信息。我们对多药耐药(MDR)和广泛耐药(XDR)进行了全基因组测序,以鉴定 AMR 基因和携带耐药特征的基因组元件。我们的基因组发现通过蛋白质组分析得到了进一步证实。我们还对 的基因组进行了工程改造,以监测自主复制质粒和核心基因组在耐药谱中的重要性。我们的研究结果深入了解了近期霍乱分离株的基因组,并确定了几种获得的特征,包括质粒、转座子、整合性 conjugative 元件(ICEs)、致病性岛(PIs)、噬菌体和基因盒,这些特征赋予了病原体适应性。本研究提供的知识将有助于更好地了解 的进化和霍乱病的管理,为临床提供首选治疗方案提供指导。

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