The devil we know? Using sequencing and metagenomics to assess the diversity of bacteria and antimicrobial resistance captured by passive surveillance

我们认识的恶魔？

• 批准号: BB/M014088/1
• 负责人: Alison Mather
• 金额: $ 36.88万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM014088%2F1
• 关键词: devil; know; Using; sequencing; metagenomics

Antimicrobial resistance (AMR) of bacterial infections is a serious threat to public health, and in order to halt or control its rise, understanding where it comes from and how it spreads is essential. Resistance to antimicrobial drugs in non-typhoidal Salmonella (NTS), a bacterium that infects both animals and humans, is an increasing problem, one that can lead to more severe infections and complicates treatment. A great deal of our understanding of the patterns and sources of NTS and AMR is based on data from laboratory-based surveillance and from disease outbreak investigations. These systems collect data and samples from primarily clinically ill individuals, for which there is significant under-reporting and which represent only those bacteria that cause disease. Therefore, these data characterise a relatively small proportion of the overall bacterial population. The research outlined in this fellowship proposal builds on my previous experience in epidemiology, ecology and genomics, and will address five key questions: 1) How similar are NTS and AMR from clinically diseased and non-diseased hosts? 2) For common AMR patterns found in different subtypes of NTS, are the resistance genes the same? 3) How is AMR distributed between different host populations in the same location, and how well does the observed resistance correlate with identified AMR genes? 4) How does AMR in different host populations compare between an industrialised and an industrialising country? 5) How much of the total AMR in a sample, including in bacteria that cannot be grown in standard laboratory conditions, is represented by the AMR within a single organism, NTS, which can be grown in standard laboratory conditions? I will address these questions using NTS collections from Canada and Vietnam, where in each location NTS are available from diseased and non-diseased individuals. This research will be undertaken at the University of Cambridge, in conjunction with collaborators at the Oxford University Clinical Research Unit/Wellcome Trust Major Overseas Programme in Vietnam, the University of Ottawa, Canada, and the Wellcome Trust Sanger Institute, UK. Whole genome sequencing provides the highest resolution available to investigate how organisms are related to each other on a genetic level, and I will utilise this technology to assess how similar isolates from diseased and non-diseased hosts are to each other, the type and diversity of AMR found in each, and the degree of mixture of the populations of isolates from differing disease status hosts. I will also generate a pilot dataset applying metagenomic sequencing to faecal samples, examining all bacteria in the samples, including those can and cannot grow in standard laboratory conditions, and compare how well the AMR in the NTS isolate represents the AMR found within the total bacterial population. In addition, I will use these isolate collections to examine AMR and NTS from animal and human populations in Vietnam; given the global nature of the food supply and the wide variability of agricultural, political and sociological settings across the world, it is important to conduct such assessments in many different countries, as there is unlikely to be a single universal condition for AMR. If we are going to have the ability to do something to halt the rise in AMR, we need to know where it is, how well we are currently measuring it, and what we may be missing - the research encompassed by this proposal will provide important insight and critical data with which to address these questions.

细菌感染的抗菌素耐药性 (AMR) 对公共健康构成严重威胁，为了阻止或控制其上升，了解其来源和传播方式至关重要。非伤寒沙门氏菌（NTS）是一种同时感染动物和人类的细菌，其对抗菌药物的耐药性是一个日益严重的问题，可能导致更严重的感染并使治疗复杂化。我们对 NTS 和 AMR 的模式和来源的了解很大程度上是基于实验室监测和疾病暴发调查的数据。这些系统主要从临床患病个体收集数据和样本，这些数据和样本存在严重的漏报情况，并且仅代表那些引起疾病的细菌。因此，这些数据表征了总体细菌种群中相对较小的比例。本奖学金提案中概述的研究建立在我之前在流行病学、生态学和基因组学方面的经验的基础上，并将解决五个关键问题：1）临床患病宿主和非患病宿主的 NTS 和 AMR 有多相似？ 2）对于NTS不同亚型中常见的AMR模式，耐药基因是否相同？ 3) AMR 在同一地点的不同宿主群体之间如何分布，观察到的耐药性与已识别的 AMR 基因的相关性如何？ 4) 工业化国家和正在工业化国家之间不同东道国人群的抗菌素耐药性如何比较？ 5) 样品（包括不能在标准实验室条件下生长的细菌）中的总 AMR 有多少是由可以在标准实验室条件下生长的单个生物体 NTS 内的 AMR 代表的？我将使用来自加拿大和越南的 NTS 集合来回答这些问题，在每个地点，NTS 都可以从患病和未患病的个体中获得。这项研究将在剑桥大学与牛津大学临床研究中心/越南威康信托主要海外项目、加拿大渥太华大学和英国威康信托桑格研究所的合作者共同进行。全基因组测序提供了最高分辨率，可用于研究生物体在基因水平上如何相互关联，我将利用这项技术来评估患病宿主和非患病宿主的分离株之间的相似程度、每个宿主中发现的 AMR 的类型和多样性，以及来自不同疾病状态宿主的分离株群体的混合程度。我还将生成一个试验数据集，将宏基因组测序应用于粪便样本，检查样本中的所有细菌，包括那些可以和不能在标准实验室条件下生长的细菌，并比较 NTS 分离株中的 AMR 与总细菌群体中发现的 AMR 的代表程度。此外，我将使用这些分离株来检查越南动物和人群中的 AMR 和 NTS；鉴于粮食供应​​的全球性以及世界各地农业、政治和社会环境的巨大差异，在许多不同国家进行此类评估非常重要，因为抗菌素耐药性不太可能存在单一的普遍条件。如果我们有能力采取措施阻止抗菌素耐药性的上升，我们需要知道它在哪里，我们目前测量它的情况如何，以及我们可能遗漏了什么——该提案所包含的研究将为解决这些问题提供重要的见解和关键数据。

项目成果

Mobility of antimicrobial resistance across serovars and disease presentations in non-typhoidal Salmonella from animals and humans in Vietnam.

• DOI: 10.1099/mgen.0.000798
• 发表时间: 2022-05
• 期刊: MICROBIAL GENOMICS
• 影响因子: 3.9
• 作者: Bloomfield, Samuel;Vu Thuy Duong;Ha Thanh Tuyen;Campbell, James, I;Thomson, Nicholas R.;Parkhill, Julian;Hoang Le Phuc;Tran Thi Hong Chau;Maskell, Duncan J.;Perron, Gabriel G.;Nguyen Minh Ngoc;Lu Lan Vi;Adriaenssens, Evelien M.;Baker, Stephen;Mather, Alison E.
• 通讯作者: Mather, Alison E.

Vibrio cholerae Serogroup O139: Isolation from Cholera Patients and Asymptomatic Household Family Members in Bangladesh between 2013 and 2014.

• DOI: 10.1371/journal.pntd.0004183
• 发表时间: 2015-11
• 期刊: PLoS neglected tropical diseases
• 影响因子: 3.8
• 作者: Chowdhury F;Mather AE;Begum YA;Asaduzzaman M;Baby N;Sharmin S;Biswas R;Uddin MI;LaRocque RC;Harris JB;Calderwood SB;Ryan ET;Clemens JD;Thomson NR;Qadri F
• 通讯作者: Qadri F

Global and regional dissemination and evolution of Burkholderia pseudomallei.

• DOI: 10.1038/nmicrobiol.2016.263
• 发表时间: 2017-01-23
• 期刊: Nature microbiology
• 影响因子: 28.3
• 作者: Chewapreecha C;Holden MT;Vehkala M;Välimäki N;Yang Z;Harris SR;Mather AE;Tuanyok A;De Smet B;Le Hello S;Bizet C;Mayo M;Wuthiekanun V;Limmathurotsakul D;Phetsouvanh R;Spratt BG;Corander J;Keim P;Dougan G;Dance DA;Currie BJ;Parkhill J;Peacock SJ
• 通讯作者: Peacock SJ

Integrated view of Vibrio cholerae in the Americas.

美洲霍乱弧菌的综合视图。

• DOI: 10.17863/cam.36742
• 发表时间: 2017
• 作者: Domman D

Whole genome sequencing of Shigella sonnei through PulseNet Latin America and Caribbean: advancing global surveillance of foodborne illnesses.

• DOI: 10.1016/j.cmi.2017.03.021
• 发表时间: 2017-11
• 期刊: Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
• 作者: Baker KS;Campos J;Pichel M;Della Gaspera A;Duarte-Martínez F;Campos-Chacón E;Bolaños-Acuña HM;Guzmán-Verri C;Mather AE;Diaz Velasco S;Zamudio Rojas ML;Forbester JL;Connor TR;Keddy KH;Smith AM;López de Delgado EA;Angiolillo G;Cuaical N;Fernández J;Aguayo C;Morales Aguilar M;Valenzuela C;Morales Medrano AJ;Sirok A;Weiler Gustafson N;Diaz Guevara PL;Montaño LA;Perez E;Thomson NR
• 通讯作者: Thomson NR