PT - JOURNAL ARTICLE AU - Kern Rei Chng AU - Chenhao Li AU - Denis Bertrand AU - Amanda Hui Qi Ng AU - Junmei Samantha Kwah AU - Hwee Meng Low AU - Chengxuan Tong AU - Licheng Xu AU - Tamar V. Av-Shalom AU - Chiea Chuen Khor AU - MetaSUB Consortium AU - Swaine L. Chen AU - Christopher E. Mason AU - Oon Tek Ng AU - Kalisvar Marimuthu AU - Brenda Ang AU - Niranjan Nagarajan TI - Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment AID - 10.1101/644740 DP - 2019 Jan 01 TA - bioRxiv PG - 644740 4099 - http://biorxiv.org/content/early/2019/05/21/644740.short 4100 - http://biorxiv.org/content/early/2019/05/21/644740.full AB - There is growing attention surrounding hospital acquired infections (HAIs) due to high associated healthcare costs, compounded by the scourge of widespread multi-antibiotic resistance. Although hospital environment disinfection is well acknowledged to be key for infection control, an understanding of colonization patterns and resistome profiles of environment-dwelling microbes is currently lacking. We report the first extensive genomic characterization of microbiomes (355), common HAI-associated microbes (891) and transmissible drug resistance cassettes (1435) in a tertiary hospital environment based on a 2-timepoint sampling of 179 sites from 45 beds. Deep shotgun metagenomic sequencing unveiled two distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human microbiome influenced environments that display corresponding patterns of divergence over space and time. To study common nosocomial pathogens that were typically present at low abundances, a combination of culture enrichment and long-read nanopore sequencing was used to obtain thousands of high contiguity genomes (2347) and closed plasmids (5910), a significant fraction of which (>58%) are not represented in current sequence databases. These high-quality assemblies and metadata enabled a rich characterization of resistance gene combinations, plasmid architectures, and the dynamic nature of hospital environment resistomes and their reservoirs. Phylogenetic analysis identified multidrug resistant clonal strains as being more widely disseminated and stably colonizing across hospital sites. Further genomic comparisons with clinical isolates across multiple species supports the hypothesis that multidrug resistant strains can persist in the hospital environment for extended periods (>8 years) to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in the hospital environment and establishes the feasibility of systematic genomic surveys to help target resources more efficiently for preventing HAIs.