Tackling AMR in Wastewater Systems with Sneaky Bacteria

利用狡猾的细菌应对废水系统中的抗菌素耐药性

基本信息

  • 批准号:
    EP/R036705/1
  • 负责人:
  • 金额:
    $ 32.09万
  • 依托单位:
  • 依托单位国家:
    英国
  • 项目类别:
    Research Grant
  • 财政年份:
    2018
  • 资助国家:
    英国
  • 起止时间:
    2018 至 无数据
  • 项目状态:
    已结题

项目摘要

Domestic wastewater treatment is among the main reasons why community health has improved dramatically since Victorian Times. Waste treatment plants (WTPs) effectively remove pathogens, carbon, and nitrogen, creating a healthier environment and reducing the waterborne infectious disease. However, WTPs were never designed to remove contemporary contaminants, such as antimicrobial resistant bacteria (ARB) or genes (ARG). Current WTPs reduce many ARBs/ARGs from wastes, but the "worst" sub-fraction of ARGs increase in WTPs, especially multi-ARGs (MRGs) that create the potential for indestructible pathogens. Researchers have been studying why multidrug resistance (MDR) is selected in WTPs. However, the cause is unknown, which impacts the long-term resilience of our water infrastructure.In the 1950s, German researchers observed a strange bacterial form in activated sludge (AS) in WTPs, called L-form bacteria. L-forms are "normal" bacteria that temporarily lose their cell wall. Although interesting, this observation was not pursued further. However, medical researchers recently discovered that L-form bacteria are common in MDR urinary tract (u-tract) infections, and my speculation is that L-form bacteria, which are intrinsically MDR, might be the "unknown" cause of MDR in WTP effluents. To test this bright idea, ~40 samples were collected from two UK WTPs and very high levels of L-form strains were found, especially in AS floc. Further, all L-form strains were putative "gut" bacteria, implying MDR in WTP effluents may be due to the selective survival of gut-originated L-form bacteria that "hide" in floc (in pseudo-dormant state) and then "sneak" back into WTP effluents because they survive waste treatment in their L-form state. The project do the following: - Develop better methods for detecting L-forms in wastewater;- Quantify environmental conditions in WTPs where L-form bacteria are selected and hide, and determine what triggers their reactivation;- Identify gene expression targets that promote/repress the L-form state and identify specific locations in WTPs where L-forms can be selectively destroyed; and- Perform bench- and pilot-scale reactor work to develop new treatment strategies to reduce MDR, especially aimed at reducing L-form survival in WTPs effluents.We already have >700 microbial MDR isolates from WTPs in the UK, Spain and India, although few have been tested for L-form development. However, early data suggest L-forms are common in AS, consistent with German observations. Within this context, work initially will focus on characterising our current MDR isolates in detail, especially categorising strains prone to L-formation and also identifying the presence and absence of key "L-form trigger genes" (in our isolates). Target genes will be refined and tested for diagnostics of L-forms, and also how their prevalence and local environments relate to MDR indictors (using qPCR, NGS and resistomics). With these data, structured sampling will be performed with three industrial partners on eight full-scale WTPs with different biological treatment technologies to identify "hot spots" of L-form selection and survival. Locale data will be used to guide lab- and pilot-scale testing of new and retrofit technologies to reduce MDR levels in WTP effluents, which will inform strategies for increasing resilience in our urban water infrastructure, especially reducing AMR spread and protecting community health. This proposal will deliver key outcomes for A Healthy and Resilient Nation, specifically H2, H3, R2 and R3, because it will generate basic and practical data that impacts all WTP designs in future; designs to reduce MRGs released to the environment. Beyond this outcome, transcendent discoveries will be made on the genetics, ecology and selection of L-form strains, which will inform the medical community on MDR infections and also improve diagnostics in both clinical and environmental settings.
自维多利亚时代以来,生活污水处理是社区健康状况显著改善的主要原因之一。废物处理厂(WTP)有效地去除病原体,碳和氮,创造更健康的环境,减少水传播的传染病。然而,WTP从未被设计用于去除当代污染物,如抗微生物耐药细菌(ARB)或基因(ARG)。目前的WTP减少了废物中的许多ARB/ARG,但ARG的“最坏”子部分在WTP中增加,特别是多ARG(MRG),它可能产生不可摧毁的病原体。研究人员一直在研究为什么多药耐药(MDR)在WTP中被选择。然而,原因不明,这影响了我们的水基础设施的长期弹性。在20世纪50年代,德国研究人员在WTP的活性污泥(AS)中观察到一种奇怪的细菌形式,称为L型细菌。L型是暂时失去细胞壁的“正常”细菌。虽然这一观察结果很有意思,但没有进一步探讨。然而,医学研究人员最近发现,L型细菌是常见的MDR尿路(U-道)感染,我的猜测是,L型细菌,这是本质上的MDR,可能是“未知”的原因MDR在污水处理厂的污水。为了验证这个好主意,从两个英国WTP收集了约40个样本,发现了非常高水平的L型菌株,特别是在AS絮凝物中。此外,所有L型菌株都是推定的“肠道”细菌,这意味着WTP流出物中的MDR可能是由于肠道来源的L型细菌的选择性存活,这些细菌“隐藏”在絮凝物中(处于假休眠状态),然后“潜入”回WTP流出物中,因为它们以L型状态在废物处理中存活。该项目执行以下操作:- 确定促进/抑制L型状态的基因表达靶点,并确定在WTP中可以选择性破坏L型的特定位置;以及-开展实验室和中试规模的反应器工作,以开发新的处理策略来减少MDR,特别是旨在减少WTP流出物中的L型存活。我们已经从英国,西班牙和印度的WTP中分离出超过700种微生物MDR,尽管很少有人进行L型发育的测试。然而,早期的数据表明,L型在AS中很常见,与德国的观察结果一致。在此背景下,工作最初将集中在详细描述我们目前的MDR分离株,特别是对倾向于L型形成的菌株进行分类,并确定关键的“L型触发基因”(在我们的分离株中)的存在和不存在。将对靶基因进行优化和测试,以用于L型的诊断,以及它们的流行率和局部环境与MDR指标的关系(使用qPCR、NGS和耐药基因组学)。有了这些数据,将与三个工业合作伙伴对八个采用不同生物处理技术的全规模WTP进行结构化抽样,以确定L型选择和生存的“热点”。现场数据将用于指导新技术和改造技术的实验室和中试规模测试,以降低污水处理厂废水中的MDR水平,这将为提高城市供水基础设施的恢复力,特别是减少AMR传播和保护社区健康提供信息。该提案将为一个健康和有弹性的国家提供关键成果,特别是H2,H3,R2和R3,因为它将产生影响未来所有WTP设计的基本和实用数据;设计减少MRG释放到环境中。除了这一结果,还将在L型菌株的遗传学、生态学和选择方面取得卓越的发现,这将为医学界提供MDR感染方面的信息,并改善临床和环境背景下的诊断。

项目成果

期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
A Simple Approach to Predicting the Reliability of Small Wastewater Treatment Plants
  • DOI:
    10.3390/w11112397
  • 发表时间:
    2019-11-01
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Bunce, Joshua T.;Graham, David W.
  • 通讯作者:
    Graham, David W.
Shedding of SARS-CoV-2 in feces and urine and its potential role in person-to-person transmission and the environment-based spread of COVID-19.
  • DOI:
    10.1016/j.scitotenv.2020.141364
  • 发表时间:
    2020-12-20
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Jones DL;Baluja MQ;Graham DW;Corbishley A;McDonald JE;Malham SK;Hillary LS;Connor TR;Gaze WH;Moura IB;Wilcox MH;Farkas K
  • 通讯作者:
    Farkas K
Strategic Approach for Prioritising Local and Regional Sanitation Interventions for Reducing Global Antibiotic Resistance
  • DOI:
    10.3390/w11010027
  • 发表时间:
    2019-01-01
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Graham, David W.;Giesen, Myra J.;Bunce, Joshua T.
  • 通讯作者:
    Bunce, Joshua T.
Reusing Treated Wastewater: Consideration of the Safety Aspects Associated with Antibiotic-Resistant Bacteria and Antibiotic Resistance Genes
  • DOI:
    10.3390/w10030244
  • 发表时间:
    2018-03-01
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Hong, Pei-Ying;Julian, Timothy R.;Manaia, Celia M.
  • 通讯作者:
    Manaia, Celia M.
EMBRACE-WATERS statement: Recommendations for reporting of studies on antimicrobial resistance in wastewater and related aquatic environments.
Abrace-Waters声明:报告废水和相关水生环境中抗菌素耐药性研究的建议。
  • DOI:
    10.1016/j.onehlt.2021.100339
  • 发表时间:
    2021-12
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hassoun-Kheir N;Stabholz Y;Kreft JU;de la Cruz R;Dechesne A;Smets BF;Romalde JL;Lema A;Balboa S;García-Riestra C;Torres-Sangiao E;Neuberger A;Graham D;Quintela-Baluja M;Stekel DJ;Graham J;Pruden A;Nesme J;Sørensen SJ;Hough R;Paul M
  • 通讯作者:
    Paul M
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David Graham其他文献

Kenneth Burke’s pentad: a state of the discipline review, 2001-2010
肯尼思·伯克的五联体:2001-2010 年学科审查状况
  • DOI:
  • 发表时间:
    2011
  • 期刊:
  • 影响因子:
    0
  • 作者:
    David Graham
  • 通讯作者:
    David Graham
Uptake of new drugs in the early post‐approval period in the Mini‐Sentinel distributed database
Mini-Sentinel 分布式数据库中批准后早期新药的使用情况
  • DOI:
    10.1002/pds.4013
  • 发表时间:
    2016
  • 期刊:
  • 影响因子:
    2.6
  • 作者:
    Katrina Mott;David Graham;S. Toh;J. Gagne;Mark S Levenson;Yong Ma;M. Reichman
  • 通讯作者:
    M. Reichman
The chef as an emotional and aesthetic labourer; an employee in transition
厨师作为情感和审美劳动者;
  • DOI:
  • 发表时间:
    2015
  • 期刊:
  • 影响因子:
    0
  • 作者:
    David Graham
  • 通讯作者:
    David Graham
Outcomes of Arthroscopic-Assisted Distal Radius Fracture Volar Plating: A Meta-Analysis
  • DOI:
    10.1016/j.jhsa.2021.11.025
  • 发表时间:
    2022-04-01
  • 期刊:
  • 影响因子:
  • 作者:
    Zaid Shihab;Brahman Sivakumar;David Graham;Francisco del Piñal
  • 通讯作者:
    Francisco del Piñal
SSR180711, a Novel Selective α7 Nicotinic Receptor Partial Agonist: (1) Binding and Functional Profile
SSR180711,一种新型选择性α7 烟碱受体部分激动剂:(1)结合和功能特性
  • DOI:
    10.1038/sj.npp.1301189
  • 发表时间:
    2006-10-04
  • 期刊:
  • 影响因子:
    7.100
  • 作者:
    Bruno Biton;Olivier E Bergis;Frédéric Galli;Alain Nedelec;Alistair W Lochead;Samir Jegham;Danielle Godet;Christophe Lanneau;Raphaël Santamaria;Françoise Chesney;Jacques Léonardon;Patrick Granger;Marc W Debono;Georg A Bohme;Frédéric Sgard;François Besnard;David Graham;Annick Coste;André Oblin;Olivier Curet;Xavier Vigé;Corinne Voltz;Liliane Rouquier;Josiane Souilhac;Vincent Santucci;Christiane Gueudet;Dominique Françon;Régis Steinberg;Guy Griebel;Florence Oury-Donat;Pascal George;Patrick Avenet;Bernard Scatton
  • 通讯作者:
    Bernard Scatton

David Graham的其他文献

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{{ truncateString('David Graham', 18)}}的其他基金

Testing the Supernova Hypothesis Using 3He and 60Fe in Marine Sediments
使用海洋沉积物中的 3He 和 60Fe 检验超新星假说
  • 批准号:
    1836083
  • 财政年份:
    2019
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Standard Grant
Collaborative Research: Carbon-Helium-Argon Isotope Relations at High-3He/4He Hotspots and Implications for Mantle Dynamics
合作研究:高 3He/4He 热点的碳-氦-氩同位素关系及其对地幔动力学的影响
  • 批准号:
    1763255
  • 财政年份:
    2018
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Standard Grant
Dynamics of Antimicrobial Resistance in the Urban Water Cycle in Europe
欧洲城市水循环中抗菌素耐药性的动态
  • 批准号:
    MR/P028195/1
  • 财政年份:
    2017
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Research Grant
Collaborative Research: Examining Upper Mantle Volatile History Through Isotopic Variations of Carbon, Nitrogen, Hydrogen and Noble Gases in Undegassed Mid-Ocean Ridge Basalts
合作研究:通过未脱气的大洋中脊玄武岩中碳、氮、氢和稀有气体的同位素变化检查上地幔挥发历史
  • 批准号:
    1558798
  • 财政年份:
    2016
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Standard Grant
Quantifying Spatial AMR Patterns across Urban and Rural Landscapes
量化城乡景观的空间 AMR 模式
  • 批准号:
    NE/N020626/1
  • 财政年份:
    2016
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Research Grant
Collaborative Research: An Isotopic and Trace Element Study of Links Between Source Heterogeneity and Mantle Melting Beneath the Southeast Indian Ridge
合作研究:东南印度洋中脊下方源异质性与地幔融化之间联系的同位素和微量元素研究
  • 批准号:
    1357061
  • 财政年份:
    2014
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Standard Grant
Collaborative Research: Mantle Volatiles in an Emerging Ocean Basin: H2O, CO2, and He & Ar Isotopes in Basalts from the Gulf of Aden Spreading Center System
合作研究:新兴洋盆中的地幔挥发物:H2O、CO2 和 He
  • 批准号:
    1259964
  • 财政年份:
    2013
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Standard Grant
CAREER: Energy-Efficient Sensor Networks Using Analog Signal Processing
职业:使用模拟信号处理的节能传感器网络
  • 批准号:
    1148815
  • 财政年份:
    2012
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Continuing Grant
Impact of methanotrophs, methanogens and geochemical conditions on net methane flux to the atmosphere from Arctic soils
甲烷氧化菌、产甲烷菌和地球化学条件对北极土壤向大气净甲烷通量的影响
  • 批准号:
    NE/J01446X/1
  • 财政年份:
    2012
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Research Grant
Impact of copper geochemistry on the selection and abundance of methane-oxidizing bacteria in Arctic soils
铜地球化学对北极土壤中甲烷氧化细菌的选择和丰度的影响
  • 批准号:
    NE/G01003X/1
  • 财政年份:
    2010
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Research Grant

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  • 财政年份:
    2024
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Research Grant
制御性能と安全性を両立したAMRのSafety-Criticalな準最適制御系設計
AMR 的安全关键半优化控制系统设计,平衡控制性能和安全性
  • 批准号:
    24K07539
  • 财政年份:
    2024
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Developing a new generation of tools for predicting novel AMR mutation profiles using generative AI
使用生成人工智能开发新一代工具来预测新型 AMR 突变谱
  • 批准号:
    BB/Z514305/1
  • 财政年份:
    2024
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Research Grant
Aerobiome based genomic surveillance of fungicide resistance to track the development and spread of AMR in plant pathogens and the wider environment
基于空气生物组的杀菌剂抗性基因组监测,以追踪植物病原体和更广泛环境中 AMR 的发展和传播
  • 批准号:
    MR/Y034023/1
  • 财政年份:
    2024
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Research Grant
Canadian antibiotic prescribing feedback initiative: Building a national framework to combat antimicrobial resistance in primary care (CANBuild-AMR)
加拿大抗生素处方反馈倡议:建立国家框架以应对初级保健中的抗菌药物耐药性 (CANBuild-AMR)
  • 批准号:
    487020
  • 财政年份:
    2023
  • 资助金额:
    $ 32.09万
  • 项目类别:
    Operating Grants
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