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

抗生素耐药性正成为人类和环境健康面临的最紧迫问题之一。最近，对万古霉素的耐药性？最后呢?抗生素，被报道，表明我们正在迅速用尽手段来对抗细菌传染病。另一方面，杀菌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仍然不受限制。因此，在环境或诊所中，消毒剂经常与抗生素共存，其浓度通常高于抗生素。美国微生物学会（American Academy of Microbiology）最近的一份报告指出，由于消毒剂无处不在，并能引起广泛的耐药性，如外排泵耐药性，因此它们可能比抗生素本身对抗生素的未来构成更大的威胁。消毒剂完全有可能导致了我们今天面临的一些非常严重的细菌耐药性问题的出现。本研究的目的是为广泛使用的一类消毒剂季铵化合物（QACs）对抗生素耐药性（AbR）的出现和增殖的影响提供新的定量见解。此外，QACs本身是一种重要的危害，因为它们是持久性的，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有毒。QACs被污泥、沉积物、粘土和矿物质强烈吸附，吸附通常优于好氧环境介质中的生物降解，导致QACs转移到缺氧/厌氧隔间。QACs在缺氧/厌氧系统中的命运尚不清楚；但它对治疗QAC毒性和共选AbR具有重要的实际意义。因此，该项目的另一个目标是更好地了解在工程和自然系统中有氧和厌氧条件下导致QAC生物降解的条件和遗传决定因素。提出的研究建立在qac驱动AbR增殖的初步证据的基础上。拟议中的研究具有潜在的变革性。如上所述，迄今为止，AbR与抗微生物剂（QACs）在缺氧/厌氧条件下的生物转化之间的联系尚未得到系统评估。这项研究应该会对这些联系产生重要的新见解，这可能广泛适用于其他类型的AbR致病因子，包括人为的和自然的，可能导致AbR病因的范式转变。质量保证物质对人类和环境健康构成重大风险。该研究将阐明选定的QACs的生物转化及其在代表工程和自然系统的生物系统中共同选择AbR决定因子的潜力。本研究的结果将有助于更好地理解质量保证品作为环境危害的重要性，促进制定减轻其不利影响的战略，并帮助工业界以及州和联邦监管机构制定健全的政策和风险评估战略。研究结果将通过报告发布到美国国家科学基金会和我们的个人网站上，并在同行评议的期刊上发表，并在专业学会的会议上发表。学生训练是拟议项目的一个组成部分，发生在课堂和研究实验室。两名博士生，一名环境工程专业，一名环境微生物专业，将得到支持和交叉培训。这项研究将支持针对不同学科本科生的积极教育组成部分。双方将每年开展由项目负责人与合作项目负责人共同开发的“理工本科生交流项目”。他们将从环境工程和生物学本科专业招收优秀的、不同种族的学生，他们将从事与拟议的研究项目相关的研究。他们还将每年资助2名本科生，并将每年招收4名学生，这些学生将获得独立研究学分，这样总共18名学生（9名生物学和9名工程学）将在这个为期3年的项目中接受培训。HGT-U交换项目的成功与否将取决于学生在本科阶段的学习进度。评估标准将包括跟踪学生在科学和工程课程上的学术成就，与同龄人相比，选修课程的选择，以及参与工程和科学会议。

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.