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Advancing Understanding of Diversity and Antimicrobial Resistance in Indoor Microbiomes

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The importance of understanding indoor microbial exposure is increasingly recognized, particularly concerning the emergence of pathogens and antimicrobial resistance. With the advancements of sequencing technologies, our capability of exploring indoor microbial communities has dramatically increased. However, huge challenges remain to translate sequence-based knowledge to actionable interpretations to support human health and environmental sustainability. Specifically, we urgently need more effective, untargeted surveillance methods for environmental microbiomes in healthcare facilities. We need to conduct more and better monitoring of tolerance to antimicrobials that were long immune from concern (e.g., chlorhexidine) as it is emerging in hospital environments. We also need to expand the toolkit for evidence synthesis studies in the field of environmental microbiomes to fully unleash the potential of indoor microbiome research and to reveal more generalizable phenomena and mechanisms. In this dissertation, I developed an improved metagenomics-based surveillance workflow with enhanced ability to handle low-biomass samples, distinguish viability, be quantitative, and estimate sequencing resources. The workflow not only can serve as a guidance for environmental surveillance practices but also enhances our understanding of surface microbiomes. I investigated chlorhexidine resistance in the hospital environment by combining controlled microcosm experiments and field surveys. My work uncovered the persistence patterns of chlorhexidine on indoor surfaces in response to disinfection and cleaning practices. I also found that chlorhexidine tolerance was widespread in a medical intensive care unit environment, and sinks were a dominant reservoir regarding chlorhexidine tolerance. This knowledge will help improve clinical application of chlorhexidine. Additionally, I developed an R package, RefDeduR, that performs accurate and high-throughput reference deduplication for large datasets to promote broader applications of evidence synthesis research (e.g., in indoor microbiomes). Taken together, this dissertation enhances our knowledge of diversity and antimicrobial resistance in indoor microbiomes as well as improves our capability for future exploration. The outcomes of this dissertation will not only facilitate future research in the field, but also inform clinical and epidemiological surveillance, disinfection and cleaning practices, and building design. Ultimately these will lead to better infection prevention and health promotion.

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