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)是对公共健康的严重威胁，为了阻止或控制其上升，了解它的来源和传播方式是至关重要的。非伤寒沙门氏菌(NTS)是一种同时感染动物和人类的细菌，对抗菌药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的模式和来源的大量了解是基于实验室监测和疾病暴发调查的数据。这些系统从主要临床患病的人那里收集数据和样本，对这些人的报告严重不足，并且只代表那些导致疾病的细菌。因此，这些数据在细菌总数中所占比例相对较小。这份奖学金提案中概述的研究建立在我以前在流行病学、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)来自临床患病和非患病宿主的NTS和AMR有多相似？2)对于在不同NTS亚型中发现的常见AMR模式，抗药性基因是否相同？3)AMR如何在同一地点的不同宿主群体之间分布，以及观察到的抗药性与已鉴定的AMR基因的相关性如何？4)不同宿主群体中的AMR在工业化国家和工业化国家之间的比较如何？5)样本中AMR总量的多少，包括不能在标准实验室条件下生长的细菌中的AMR，是由可以在标准实验室条件下生长的单个有机体NTS中的AMR代表的吗？我将使用来自加拿大和越南的NTS收集来解决这些问题，在每个地点，NTS都可以从患病和未患病的个人那里获得。这项研究将由剑桥大学与牛津大学临床研究部/惠康信托越南主要海外项目、加拿大渥太华大学和英国惠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现有的最高分辨率来研究生物如何在基因水平上相互关联，我将利用这项技术来评估来自患病和未患病宿主的分离株彼此之间的相似程度、在每个宿主中发现的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。我还将生成一个试点数据集，将元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代表在总细菌种群中发现的AMR的情况。此外，我将使用这些孤立的收集来检查来自越南动物和人类群体的AMR和NTS；鉴于食品供应的全球性以及世界各地农业、政治和社会学背景的广泛多样性，在许多不同的国家进行此类评估是重要的，因为AMR不太可能有单一的普遍条件。如果我们要做一些事情来阻止AMR的上升，我们需要知道它在哪里，我们目前衡量它的情况如何，以及我们可能遗漏了什么--这项提案包含的研究将提供重要的洞察力和关键数据，以解决这些问题。

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