Disinfectant-Induced Antibiotic Resistance: Relevance, Mechanisms and Practical Considerations

消毒剂引起的抗生素耐药性：相关性、机制和实际考虑

• 批准号: 0967130
• 负责人: Spyros Pavlostathis
• 金额: $ 40.5万
• 依托单位: Georgia Tech Research Corporation
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2013-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0967130&HistoricalAwards=false
• 关键词: Disinfectant; Induced; Antibiotic; Resistance; Relevance

Pavlostathis, SpyrosCBET-0967130Resistance to antibiotics is becoming one of the most pressing problems for human and environmental health. Recently, resistance to vancomycin, the ?last resort? antibiotic, was reported, indicating that we are quickly running out of means to fight against bacterial infectious diseases. Biocides and disinfectants, on the other hand, are biologically active agents, whose use in homes, hospitals, industrial or agricultural facilities remains essentially unconstrained. Consequently, disinfectants are frequently co-occurring with antibiotics in the environment or the clinic and their concentrations are typically higher than that of antibiotics. Because they are ubiquitous and can induce broad resistance capabilities like efflux pump resistance, disinfectants may represent a more important threat to the future of antibiotics than the antibiotics themselves according to a recent report by the American Academy of Microbiology, which states ?It is entirely possible that disinfectants have contributed to the rise of some of the very serious problems in resistance that we face today with the bacteria?. The goal of this research is to provide new quantitative insights into the effects of a widely used class of disinfectants, the quaternary ammonium compounds (QACs), on the emergence and proliferation of antibiotic resistance (AbR). Further, QACs represent an important hazard themselves because they are persistent, especially under anaerobic conditions, and hence, toxic to aquatic life and non-target organisms in the environment. QACs are strongly sorbed onto sludge, sediments, clays, and minerals and sorption generally outcompetes biodegradation in aerobic environmental media, leading to the transfer of QACs to anoxic/anaerobic compartments. The fate of QACs in anoxic/anaerobic systems is not well understood; but it has important practical implications for remedying QAC toxicity and the co-selected AbR. Therefore, another goal of this project is to better understand the conditions and genetic determinants that lead to QAC biodegradation under aerobic and anaerobic conditions in both engineered and natural systems. The proposed research builds upon preliminary evidence that indicates QAC-driven proliferation of AbR. The proposed research is potentially transformative. As stated above, the links between AbR and the biotransformation of antimicrobial agents (QACs in this case) under anoxic/anaerobic conditions have not been systematically assessed to date. This study should result in significant new insights into these links, which may apply broadly to other classes of AbR-causing agents, both anthropogenic and natural, potentially resulting in a paradigm shift as to the causes of AbR.QACs pose significant risks to human and environmental health. The proposed research will elucidate the biotransformation of selected QACs and their potential for co-selection of AbR determinants in biological systems representing both engineered and natural systems. The results of this study will provide a better understanding of the importance of QACs as environmental hazards and facilitate the development of strategies to mitigate their adverse effects and to aid industry, as well as state and federal regulatory agencies in the development of sound policies and risk assessment strategies. Findings will be disseminated via reports to NSF and our personal websites, and by publishing in peer-reviewed journals and presenting at meetings of professional societies. Student training is an integral part of the proposed project, occurring in both the classroom and research laboratory. Two PhD students, one majoring in Environmental Engineering and one in Environmental Microbiology, will be supported and cross trained. This research will support an active educational component targeting undergraduate students from different disciplines. Each year, we will conduct the HGT-U (Hosting Ga-Tech Undergraduates) Exchange Program developed by the PI and co-PI. They will recruit outstanding and ethnically diverse students from the environmental engineering and biology undergraduate programs who will engage in research related to the proposed research project. They will also support 2 undergraduates per year and will recruit an additional 4 students per year who will receive independent research credits so that a total of 18 (9 biology and 9 engineering) students will be trained over the course of the 3-year project. The success of the HGT-U exchange program will be determined by following students as they progress through their undergraduate education. Assessment criteria will include tracking academic achievement in the student's science and engineering courses compared to peers, choice of electives, and participation in engineering and scientific meetings and conferences.

Pavlostathis，SpyrosCBET-0967130抗生素耐药性正在成为人类和环境健康最紧迫的问题之一。最近，耐万古霉素，？最后一招？据报道，抗生素，这表明我们正在迅速耗尽对抗细菌传染病的手段。另一方面，杀生物剂和消毒剂是生物活性剂，其在家庭、医院、工业或农业设施中的使用基本上不受限制。 因此，在环境或临床中，消毒剂经常与抗生素共存，其浓度通常高于抗生素。由于它们无处不在，并且可以诱导广泛的抗性能力，如外排泵抗性，根据美国微生物学会最近的一份报告，消毒剂可能对抗生素的未来构成比抗生素本身更重要的威胁。完全有可能是消毒剂导致了一些非常严重的耐药性问题的出现，这些问题就是我们今天所面临的细菌。本研究的目的是提供新的定量见解，一类广泛使用的消毒剂，季铵化合物（QAC），对抗生素耐药性（AbR）的出现和增殖的影响。此外，四季铵盐本身也是一种重要的危险，因为它们具有持久性，特别是在厌氧条件下，因此对环境中的水生生物和非目标生物具有毒性。QAC强烈吸附在污泥、沉积物、粘土和矿物质上，并且吸附作用通常胜过好氧环境介质中的生物降解作用，导致QAC转移到缺氧/厌氧区室。QAC在缺氧/厌氧系统中的命运还不清楚，但它具有重要的实际意义，补救QAC毒性和共同选择的AbR。因此，该项目的另一个目标是更好地了解在工程系统和自然系统中导致QAC在有氧和厌氧条件下生物降解的条件和遗传决定因素。拟议的研究建立在初步证据的基础上，表明QAC驱动的AbR增殖。 拟议的研究具有潜在的变革性。如上所述，到目前为止，还没有系统地评估过缺氧/厌氧条件下抗微生物剂（在这种情况下为QAC）的生物转化与抗微生物剂之间的联系。这项研究应导致对这些联系的重要新见解，这可能广泛适用于其他类别的ABR引起的代理人，人为和自然，可能导致一个范式转变的原因ABR. QAC对人类和环境健康构成重大风险。拟议的研究将阐明选定的QAC的生物转化及其在生物系统中代表工程和自然系统的AbR决定因素的共同选择的潜力。本研究的结果将提供一个更好的理解的重要性QAC的环境危害，并促进战略的发展，以减轻其不利影响，并帮助行业，以及州和联邦监管机构在制定健全的政策和风险评估战略。研究结果将通过向NSF和我们的个人网站提交报告，并通过在同行评审期刊上发表和在专业协会会议上发表来传播。学生培训是拟议项目的一个组成部分，发生在教室和研究实验室。两名博士生，一名主修环境工程，一名主修环境微生物学，将得到支持和交叉培训。这项研究将支持一个积极的教育组成部分，针对不同学科的本科生。每年，我们将进行由PI和co-PI开发的HGT-U（主办Ga-Tech本科生）交流计划。他们将从环境工程和生物本科课程中招募优秀的和种族多样的学生，他们将从事与拟议研究项目相关的研究。他们还将每年支持2名本科生，并将每年招收4名额外的学生，他们将获得独立的研究学分，以便在3年的项目过程中培养18名（9名生物学和9名工程学）学生。HGT-U交换计划的成功将取决于以下学生，因为他们通过他们的本科教育的进展。评估标准将包括跟踪学生的科学和工程课程与同龄人相比，选修课的选择，并在工程和科学会议和会议的参与学术成就。