Rapid Genomic Characterization and Global Surveillance of Klebsiella Using Pathogenwatch
Rapid Genomic Characterization and Global Surveillance of Klebsiella Using Pathogenwatch
复制标题
DOI：
10.1101/2021.06.22.448967
复制
发表时间：
2021-06
期刊：
影响因子：
--
通讯作者：
S. Argimón;S. David;A. Underwood;M. Abrudan;N. Wheeler;M. Kekre;Khalil AbuDahab;C. Yeats;Richard J. Goater;Ben Taylor;Harry Harste;Dawn Muddyman;E. Feil;S. Brisse;K. Holt;P. Donado-Godoy;K. Ravikumar;I. Okeke;C. Carlos;D. Aanensen
中科院分区：
文献类型：
--
作者：
S. Argimón;S. David;A. Underwood;M. Abrudan;N. Wheeler;M. Kekre;Khalil AbuDahab;C. Yeats;Richard J. Goater;Ben Taylor;Harry Harste;Dawn Muddyman;E. Feil;S. Brisse;K. Holt;P. Donado-Godoy;K. Ravikumar;I. Okeke;C. Carlos;D. Aanensen
背景克雷伯氏菌属，包括著名的病原体克雷伯氏菌。肺炎，越来越多地与抗生素耐药性（AMR）有关。基于基因组的监测可以为旨在控制AMR的干预措施提供信息。然而，其广泛实施需要工具来简化生物信息学分析和公共卫生报告。方法我们开发了网络应用程序Pathogenwatch，该应用程序实现了针对克雷伯氏菌属物种的分析，用于基因组和流行病学数据的整合和可视化。我们用16,537个公共克雷伯氏菌基因组填充Pathogenwatch，以实现用户基因组的情境化。我们用来自四个中低收入国家（LMIC）的1,636个基因组展示了其特征，这些国家参加了NIHR全球健康研究单位（GHRU）关于AMR的研究。结果利用Pathogenwatch软件分析发现，GHRU基因组中存在少数克雷伯氏菌流行性耐药克隆。肺炎。然而，观察到它们的分布存在差异（例如，ST 258/512在哥伦比亚占优势，ST 231在印度占优势，ST 307在尼日利亚占优势，ST 147在菲律宾占优势）。系统发育分析，包括公共基因组的背景化，使他们的传播进行回顾性监测。特别是，我们确定了医院爆发，检测从国外引进，并发现与耐药性和毒力基因相关的克隆扩增。克雷伯氏菌O抗原和荚膜编码位点的评估。代表可能的疫苗候选者的肺炎链球菌显示三种O型（O 1-O3）占所有基因组的88.9%，而荚膜类型则多样得多。Pathogenwatch提供了一个免费的、可访问的克雷伯菌基因组实时分析平台，以帮助地方、国家和全球层面的监测。我们改进了来自GHRU参与国的基因组的代表性，进一步促进了持续监测。40-Pathogenwatch是一个免费的网络应用程序，用于分析克雷伯氏菌基因组，以帮助在地方，国家和全球层面的监测。我们通过全球卫生研究单位提高了来自中等收入国家的基因组的代表性，进一步促进了持续监测。这项工作得到了国家卫生研究所官方发展援助（ODA）资金的支持[赠款编号16_136_111]。这项研究是由国家卫生研究所利用官方发展援助资金委托进行的。本出版物中表达的观点是作者的观点，不一定是NHS，国家健康研究所或卫生部的观点。利益冲突作者：未报告利益冲突。所有作者都提交了ICMJE潜在利益冲突披露表。
Background Klebsiella species, including the notable pathogen K. pneumoniae, are increasingly associated with antimicrobial resistance (AMR). Genome-based surveillance can inform interventions aimed at controlling AMR. However, its widespread implementation requires tools to streamline bioinformatic analyses and public health reporting. Methods We developed the web application Pathogenwatch, which implements analytics tailored to Klebsiella species for integration and visualization of genomic and epidemiological data. We populated Pathogenwatch with 16,537 public Klebsiella genomes to enable contextualization of user genomes. We demonstrated its features with 1,636 genomes from four low- and middle-income countries (LMICs) participating in the NIHR Global Health Research Unit (GHRU) on AMR. Results Using Pathogenwatch, we found that GHRU genomes were dominated by a small number of epidemic drug-resistant clones of K. pneumoniae. However, differences in their distribution were observed (e.g. ST258/512 dominated in Colombia, ST231 in India, ST307 in Nigeria, ST147 in the Philippines). Phylogenetic analyses including public genomes for contextualization enabled retrospective monitoring of their spread. In particular, we identified hospital outbreaks, detected introductions from abroad, and uncovered clonal expansions associated with resistance and virulence genes. Assessment of loci encoding O-antigens and capsule in K. pneumoniae, which represent possible vaccine candidates, showed that three O-types (O1-O3) represented 88.9% of all genomes, whereas capsule types were much more diverse. Conclusions Pathogenwatch provides a free, accessible platform for real-time analysis of Klebsiella genomes to aid surveillance at local, national and global levels. We have improved representation of genomes from GHRU participant countries, further facilitating ongoing surveillance. 40-word summary Pathogenwatch is a free web-application for analysis of Klebsiella genomes to aid surveillance at local, national and global levels. We improved the representation of genomes from middle-income countries through the Global Health Research Unit on AMR, further facilitating ongoing surveillance. FUNDING This work was supported by Official Development Assistance (ODA) funding from the National Institute of Health Research [grant number 16_136_111]. This research was commissioned by the National Institute of Health Research using Official Development Assistance (ODA) funding. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. CONFLICT OF INTEREST The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.