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

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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.