Looking for the silver lining: Assessing the impact of silver in showerheads on opportunistic pathogen abundance and resistance

寻找一线希望：评估淋浴喷头中的银对机会性病原体丰度和抵抗力的影响

• 批准号: 1935378
• 负责人: Sarah Haig
• 金额: $ 33万
• 依托单位: University of Pittsburgh
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-15 至 2024-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1935378&HistoricalAwards=false
• 关键词: Looking; silver; lining; Assessing; impact; Looking; silver; lining; Assessing; impact

Water disinfection has been highly effective at preventing illness from microorganisms. However, no existing strategy can completely prevent waterborne microbial exposure through drinking, showering, and washing hands. While most microorganisms are harmless or even beneficial, some are harmful. This is particularly true for opportunistic pathogens that harm those who are sick or have weak immune systems. Opportunistic pathogens cause thousands of illnesses each year resulting in significant healthcare costs to the Nation each year. Silver (Ag) coated water fixtures have been designed to address this issue. The presence of Ag is thought to kill bacteria based on the known antimicrobial properties of this heavy metal. However, heavy metal exposure is also known to transform some bacteria into antibiotic resistant forms. Antibiotic resistance is considered one of the greatest healthcare challenges for the Nation. This raises the question of whether Ag-amended fixtures create an even larger problem than they are attempting to solve. This research is designed to resolve whether Ag amendment creates conditions that cause formation of antibiotic resistance. This will be achieved using state-of-the-science molecular techniques to explore the response of Legionella pneumophila to Ag-amended showerheads. Legionella is chosen as one of the most important opportunistic pathogens responsible for waterborne fatalities in the US. Successful completion of this research will provide results that can guide further use of Ag amended fixtures to protect human health. Benefits to society include outreach and education efforts that will enhance the STEM capability and scientific literacy of the Nation. Silver (Ag)-amended showerheads are thought to mitigate bacterial infection due to waterborne exposure through the antimicrobial properties of Ag. However, evidence of their efficacy in preventing illness due to opportunistic pathogens (OPs) like Legionella pneumophila, Pseudomonas aeruginosa, and nontuberculous mycobacteria has critical limitations. For example, conventional culture-based approaches are used to evaluate efficacy, while these techniques are known to provide false-negative results if OPs are in a viable but non-culturable state (VBNC). A second concern regarding the use of Ag is the emerging science demonstrating the potential for bacteria to develop antibiotic resistance due to exposure to heavy metals like Ag. Given these concerns, there is a critical need to determine whether Ag-amendment mitigation approaches benefit or further exacerbate human health outcomes. The hypothesis of this research is that Ag-modified showerheads will impact the microbial community in premise plumbing in a way that increases OP abundance and promotes the VBNC state, thus increasing the potential for adverse human health outcomes. This hypothesis will be tested through two research objectives to: (i) identify the impact of showerhead fixture design and influence of Ag on the microbial community in water exiting the showerheads using 16S rRNA amplicon sequencing and absolute quantification of key OPs using digital droplet PCR, and (ii) conduct targeted laboratory experiments to isolate the water and/or showerhead property(ies) governing the underlying mechanisms responsible for the abundance of L. pneumophila and their presence in the VBNC state. These will be achieved using a custom-built rig simulating a real shower environment to elucidate the critical interactions between the showerhead and the biofilm, and uncover the molecular mechanisms governing Ag-mediated inactivation or resistance development. The findings from this research will provide evidence for the efficacy of Ag-mediated mitigation strategies and the potential to induce antibiotic resistance in shower water.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

水消毒在预防微生物疾病方面非常有效。但是，没有现有的策略可以通过饮酒，淋浴和洗手完全防止水传播的微生物暴露。虽然大多数微生物无害甚至有益，但有些是有害的。对于损害生病或免疫系统较弱的机会病原体而言，尤其如此。机会性病原体每年会导致数千种疾病，每年给全国带来巨大的医疗保健费用。银色（AG）涂层的水灯具已设计用于解决此问题。人们认为，基于该重金属的已知抗菌特性杀死细菌。然而，已知重金属暴露会将一些细菌转化为抗生素耐药形式。抗生素抗性被认为是国家最大的医疗挑战之一。这就提出了一个问题，即对AG调整的固定装置是否造成了比试图解决的更大问题。这项研究旨在解决AG修订是否会产生导致抗生素耐药性形成的条件。这将是利用科学分子技术来实现的，以探索肺炎军团对Ag照明淋浴的反应。军团菌被选为负责水传播死亡的最重要的机会病原体之一。这项研究的成功完成将提供结果，可以指导进一步使用AG修订的固定装置来保护人类健康。对社会的好处包括推广和教育工作，这些工作将增强国家的STEM能力和科学素养。 银（Ag）淋浴的人被认为可以减轻通过AG的抗菌特性的水传播导致细菌感染。然而，证明它们在预防机会病原体（OP）（如肺炎军团菌，铜绿假单胞菌和非结核分枝杆菌）等疾病方面有效的证据。例如，常规基于文化的方法用于评估功效，而如果OPS处于可行但不可培养的状态（VBNC），则已知这些技术可提供错误的阴性结果。关于AG使用的第二个问题是新兴科学表明，由于暴露于AG等重金属，细菌可能产生抗生素耐药性。考虑到这些担忧，迫切需要确定缓解AG施加方法是有益还是进一步加剧人类健康结果。这项研究的假设是，Ag修饰的淋浴头会以增加op丰度并促进VBNC状态的方式影响微生物群落，从而增加了不良人类健康结果的潜力。该假设将通过两个研究目标进行测试：（i）确定淋浴喷头固定装置的设计和AG对微生物社区的影响，使用16S rRNA扩增子测序和使用数字液滴PCR对密钥OP进行淋浴的淋浴间，以及（ii）构造对供水的机制构造的机制（ii）供水（ii）造成淋浴的机制（II），以隔离水的机制（II），iS或淋浴的机制（II））（II） L.肺炎及其在VBNC状态中的存在。这些将使用定制的钻机来实现这些方法，该钻机模拟真实的淋浴环境，以阐明淋浴喷头和生物膜之间的临界相互作用，并揭示有关AG介导的灭活或耐药性发展的分子机制。这项研究的发现将为AG介导的缓解策略的功效提供证据，并有可能在淋浴水中诱导抗生素耐药性。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛的影响审查标准通过评估来进行评估的。