{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T01:23:56Z","timestamp":1778635436594,"version":"3.51.4"},"reference-count":80,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T00:00:00Z","timestamp":1591574400000},"content-version":"vor","delay-in-days":7,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Although disinfection is key to infection control, the colonization patterns and resistomes of hospital-environment microbes remain underexplored. We report the first extensive genomic characterization of microbiomes, pathogens and antibiotic resistance cassettes in a tertiary-care hospital, from repeated sampling (up to 1.5 years apart) of 179 sites associated with 45 beds. Deep shotgun metagenomics unveiled distinct ecological niches of microbes and antibiotic resistance genes characterized by biofilm-forming and human-microbiome-influenced environments with corresponding patterns of spatiotemporal divergence. Quasi-metagenomics with nanopore sequencing provided thousands of high-contiguity genomes, phage and plasmid sequences (&gt;60% novel), enabling characterization of resistome and mobilome diversity and dynamic architectures in hospital environments. Phylogenetics identified multidrug-resistant strains as being widely distributed and stably colonizing across sites. Comparisons with clinical isolates indicated that such microbes can persist in hospitals for extended periods (&gt;8 years), to opportunistically infect patients. These findings highlight the importance of characterizing antibiotic resistance reservoirs in hospitals and establish the feasibility of systematic surveys to target resources for preventing infections.<\/jats:p>","DOI":"10.1038\/s41591-020-0894-4","type":"journal-article","created":{"date-parts":[[2020,6,8]],"date-time":"2020-06-08T12:05:41Z","timestamp":1591617941000},"page":"941-951","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":219,"title":["Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment"],"prefix":"10.1038","volume":"26","author":[{"given":"Kern Rei","family":"Chng","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1182-6804","authenticated-orcid":false,"given":"Chenhao","family":"Li","sequence":"additional","affiliation":[]},{"given":"Denis","family":"Bertrand","sequence":"additional","affiliation":[]},{"given":"Amanda Hui Qi","family":"Ng","sequence":"additional","affiliation":[]},{"given":"Junmei Samantha","family":"Kwah","sequence":"additional","affiliation":[]},{"given":"Hwee Meng","family":"Low","sequence":"additional","affiliation":[]},{"given":"Chengxuan","family":"Tong","sequence":"additional","affiliation":[]},{"given":"Maanasa","family":"Natrajan","sequence":"additional","affiliation":[]},{"given":"Michael Hongjie","family":"Zhang","sequence":"additional","affiliation":[]},{"given":"Licheng","family":"Xu","sequence":"additional","affiliation":[]},{"given":"Karrie Kwan Ki","family":"Ko","sequence":"additional","affiliation":[]},{"given":"Eliza Xin Pei","family":"Ho","sequence":"additional","affiliation":[]},{"given":"Tamar V.","family":"Av-Shalom","sequence":"additional","affiliation":[]},{"given":"Jeanette Woon Pei","family":"Teo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1128-4729","authenticated-orcid":false,"given":"Chiea Chuen","family":"Khor","sequence":"additional","affiliation":[]},{"name":"MetaSUB Consortium","sequence":"additional","affiliation":[]},{"given":"David","family":"Danko","sequence":"additional","affiliation":[]},{"given":"Daniela","family":"Bezdan","sequence":"additional","affiliation":[]},{"given":"Ebrahim","family":"Afshinnekoo","sequence":"additional","affiliation":[]},{"given":"Sofia","family":"Ahsanuddin","sequence":"additional","affiliation":[]},{"given":"Chandrima","family":"Bhattacharya","sequence":"additional","affiliation":[]},{"given":"Daniel J.","family":"Butler","sequence":"additional","affiliation":[]},{"given":"Kern Rei","family":"Chng","sequence":"additional","affiliation":[]},{"given":"Francesca","family":"De Filippis","sequence":"additional","affiliation":[]},{"given":"Jochen","family":"Hecht","sequence":"additional","affiliation":[]},{"given":"Andre","family":"Kahles","sequence":"additional","affiliation":[]},{"given":"Mikhail","family":"Karasikov","sequence":"additional","affiliation":[]},{"given":"Nikos C.","family":"Kyrpides","sequence":"additional","affiliation":[]},{"given":"Marcus H. Y.","family":"Leung","sequence":"additional","affiliation":[]},{"given":"Dmitry","family":"Meleshko","sequence":"additional","affiliation":[]},{"given":"Harun","family":"Mustafa","sequence":"additional","affiliation":[]},{"given":"Beth","family":"Mutai","sequence":"additional","affiliation":[]},{"given":"Russell Y.","family":"Neches","sequence":"additional","affiliation":[]},{"given":"Amanda","family":"Ng","sequence":"additional","affiliation":[]},{"given":"Marina","family":"Nieto-Caballero","sequence":"additional","affiliation":[]},{"given":"Olga","family":"Nikolayeva","sequence":"additional","affiliation":[]},{"given":"Tatyana","family":"Nikolayeva","sequence":"additional","affiliation":[]},{"given":"Eileen","family":"Png","sequence":"additional","affiliation":[]},{"given":"Jorge L.","family":"Sanchez","sequence":"additional","affiliation":[]},{"given":"Heba","family":"Shaaban","sequence":"additional","affiliation":[]},{"given":"Maria A.","family":"Sierra","sequence":"additional","affiliation":[]},{"given":"Xinzhao","family":"Tong","sequence":"additional","affiliation":[]},{"given":"Ben","family":"Young","sequence":"additional","affiliation":[]},{"given":"Josue","family":"Alicea","sequence":"additional","affiliation":[]},{"given":"Malay","family":"Bhattacharyya","sequence":"additional","affiliation":[]},{"given":"Ran","family":"Blekhman","sequence":"additional","affiliation":[]},{"given":"Eduardo","family":"Castro-Nallar","sequence":"additional","affiliation":[]},{"given":"Ana M.","family":"Ca\u00f1as","sequence":"additional","affiliation":[]},{"given":"Aspassia D.","family":"Chatziefthimiou","sequence":"additional","affiliation":[]},{"given":"Robert W.","family":"Crawford","sequence":"additional","affiliation":[]},{"given":"Youping","family":"Deng","sequence":"additional","affiliation":[]},{"given":"Christelle","family":"Desnues","sequence":"additional","affiliation":[]},{"given":"Emmanuel","family":"Dias-Neto","sequence":"additional","affiliation":[]},{"given":"Daisy","family":"Donnellan","sequence":"additional","affiliation":[]},{"given":"Marius","family":"Dybwad","sequence":"additional","affiliation":[]},{"given":"Eran","family":"Elhaik","sequence":"additional","affiliation":[]},{"given":"Danilo","family":"Ercolini","sequence":"additional","affiliation":[]},{"given":"Alina","family":"Frolova","sequence":"additional","affiliation":[]},{"given":"Alexandra B.","family":"Graf","sequence":"additional","affiliation":[]},{"given":"David C.","family":"Green","sequence":"additional","affiliation":[]},{"given":"Iman","family":"Hajirasouliha","sequence":"additional","affiliation":[]},{"given":"Mark","family":"Hernandez","sequence":"additional","affiliation":[]},{"given":"Gregorio","family":"Iraola","sequence":"additional","affiliation":[]},{"given":"Soojin","family":"Jang","sequence":"additional","affiliation":[]},{"given":"Angela","family":"Jones","sequence":"additional","affiliation":[]},{"given":"Frank J.","family":"Kelly","sequence":"additional","affiliation":[]},{"given":"Kaymisha","family":"Knights","sequence":"additional","affiliation":[]},{"given":"Pawe\u0142 P.","family":"\u0141abaj","sequence":"additional","affiliation":[]},{"given":"Patrick K. H.","family":"Lee","sequence":"additional","affiliation":[]},{"given":"Levy","family":"Shawn","sequence":"additional","affiliation":[]},{"given":"Per","family":"Ljungdahl","sequence":"additional","affiliation":[]},{"given":"Abigail","family":"Lyons","sequence":"additional","affiliation":[]},{"given":"Gabriella","family":"Mason-Buck","sequence":"additional","affiliation":[]},{"given":"Ken","family":"McGrath","sequence":"additional","affiliation":[]},{"given":"Emmanuel F.","family":"Mongodin","sequence":"additional","affiliation":[]},{"given":"Milton Ozorio","family":"Moraes","sequence":"additional","affiliation":[]},{"given":"Niranjan","family":"Nagarajan","sequence":"additional","affiliation":[]},{"given":"Houtan","family":"Noushmehr","sequence":"additional","affiliation":[]},{"given":"Manuela","family":"Oliveira","sequence":"additional","affiliation":[]},{"given":"Stephan","family":"Ossowski","sequence":"additional","affiliation":[]},{"given":"Olayinka O.","family":"Osuolale","sequence":"additional","affiliation":[]},{"given":"Orhan","family":"\u00d6zcan","sequence":"additional","affiliation":[]},{"given":"David","family":"Paez-Espino","sequence":"additional","affiliation":[]},{"given":"Nicolas","family":"Rascovan","sequence":"additional","affiliation":[]},{"given":"Hugues","family":"Richard","sequence":"additional","affiliation":[]},{"given":"Gunnar","family":"R\u00e4tsch","sequence":"additional","affiliation":[]},{"given":"Lynn M.","family":"Schriml","sequence":"additional","affiliation":[]},{"given":"Torsten","family":"Semmler","sequence":"additional","affiliation":[]},{"given":"Osman U.","family":"Sezerman","sequence":"additional","affiliation":[]},{"given":"Leming","family":"Shi","sequence":"additional","affiliation":[]},{"given":"Le Huu","family":"Song","sequence":"additional","affiliation":[]},{"given":"Haruo","family":"Suzuki","sequence":"additional","affiliation":[]},{"given":"Denise Syndercombe","family":"Court","sequence":"additional","affiliation":[]},{"given":"Dominique","family":"Thomas","sequence":"additional","affiliation":[]},{"given":"Scott W.","family":"Tighe","sequence":"additional","affiliation":[]},{"given":"Klas I.","family":"Udekwu","sequence":"additional","affiliation":[]},{"given":"Juan A.","family":"Ugalde","sequence":"additional","affiliation":[]},{"given":"Brandon","family":"Valentine","sequence":"additional","affiliation":[]},{"given":"Dimitar I.","family":"Vassilev","sequence":"additional","affiliation":[]},{"given":"Elena","family":"Vayndorf","sequence":"additional","affiliation":[]},{"given":"Thirumalaisamy P.","family":"Velavan","sequence":"additional","affiliation":[]},{"given":"Mar\u00eda M.","family":"Zambrano","sequence":"additional","affiliation":[]},{"given":"Jifeng","family":"Zhu","sequence":"additional","affiliation":[]},{"given":"Sibo","family":"Zhu","sequence":"additional","affiliation":[]},{"given":"Christopher E.","family":"Mason","sequence":"additional","affiliation":[]},{"given":"Swaine L.","family":"Chen","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1850-1642","authenticated-orcid":false,"given":"Christopher E.","family":"Mason","sequence":"additional","affiliation":[]},{"given":"Oon Tek","family":"Ng","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0395-5633","authenticated-orcid":false,"given":"Kalisvar","family":"Marimuthu","sequence":"additional","affiliation":[]},{"given":"Brenda","family":"Ang","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0850-5604","authenticated-orcid":false,"given":"Niranjan","family":"Nagarajan","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2020,6,8]]},"reference":[{"key":"894_CR1","doi-asserted-by":"publisher","unstructured":"Fischer, M.M. & Bild, M. Hospital use of antibiotics as the main driver of infections with antibiotic-resistant bacteria\u2014a reanalysis of recent data from the European Union. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/553537 (2019).","DOI":"10.1101\/553537"},{"key":"894_CR2","unstructured":"O\u2019Neill, J. Tackling drug-resistant infections globally: final report and recommendations. In Review on Antimicrobial Resistance (2016)."},{"key":"894_CR3","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/S0140-6736(10)61458-4","volume":"377","author":"B Allegranzi","year":"2011","unstructured":"Allegranzi, B. et al. Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis. Lancet 377, 228\u2013241 (2011).","journal-title":"Lancet"},{"key":"894_CR4","doi-asserted-by":"publisher","first-page":"1198","DOI":"10.1056\/NEJMoa1306801","volume":"370","author":"SS Magill","year":"2014","unstructured":"Magill, S. S. et al. Multistate point-prevalence survey of health care-associated infections. N. Engl. J. Med. 370, 1198\u20131208 (2014).","journal-title":"N. Engl. J. Med."},{"key":"894_CR5","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/S1473-3099(13)70318-9","volume":"13","author":"R Laxminarayan","year":"2013","unstructured":"Laxminarayan, R. et al. Antibiotic resistance\u2014the need for global solutions. Lancet Infect. Dis. 13, 1057\u20131098 (2013).","journal-title":"Lancet Infect. Dis."},{"key":"894_CR6","doi-asserted-by":"publisher","first-page":"e24","DOI":"10.1056\/NEJMvcm0903599","volume":"364","author":"Y Longtin","year":"2011","unstructured":"Longtin, Y., Sax, H., Allegranzi, B., Schneider, F. & Pittet, D. Videos in clinical medicine. Hand hygiene. N. Engl. J. Med. 364, e24 (2011).","journal-title":"N. Engl. J. Med."},{"key":"894_CR7","doi-asserted-by":"publisher","first-page":"S6","DOI":"10.1016\/j.ajic.2012.12.004","volume":"41","author":"JA Otter","year":"2013","unstructured":"Otter, J. A., Yezli, S., Salkeld, J. A. & French, G. L. Evidence that contaminated surfaces contribute to the transmission of hospital pathogens and an overview of strategies to address contaminated surfaces in hospital settings. Am. J. Infect. Control 41, S6\u2013S11 (2013).","journal-title":"Am. J. Infect. Control"},{"key":"894_CR8","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1016\/S1473-3099(18)30714-X","volume":"19","author":"BG Mitchell","year":"2019","unstructured":"Mitchell, B. G. et al. An environmental cleaning bundle and health-care-associated infections in hospitals (REACH): a multicentre, randomised trial. Lancet Infect. Dis. 19, 410\u2013418 (2019).","journal-title":"Lancet Infect. Dis."},{"key":"894_CR9","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/S1473-3099(16)30413-3","volume":"17","author":"JR Price","year":"2017","unstructured":"Price, J. R. et al. Transmission of Staphylococcus aureus between health-care workers, the environment, and patients in an intensive care unit: a longitudinal cohort study based on whole-genome sequencing. Lancet Infect. Dis. 17, 207\u2013214 (2017).","journal-title":"Lancet Infect. Dis."},{"key":"894_CR10","doi-asserted-by":"publisher","first-page":"e02011-17","DOI":"10.1128\/mBio.02011-17","volume":"9","author":"RA Weingarten","year":"2018","unstructured":"Weingarten, R. A. et al. Genomic analysis of hospital plumbing reveals diverse reservoir of bacterial plasmids conferring carbapenem resistance. MBio 9, e02011-17 (2018).","journal-title":"MBio"},{"key":"894_CR11","doi-asserted-by":"publisher","first-page":"254ra126","DOI":"10.1126\/scitranslmed.3009845","volume":"6","author":"S Conlan","year":"2014","unstructured":"Conlan, S. et al. Single-molecule sequencing to track plasmid diversity of hospital-associated carbapenemase-producing Enterobacteriaceae. Sci. Transl. Med. 6, 254ra126 (2014).","journal-title":"Sci. Transl. Med."},{"key":"894_CR12","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.molmed.2015.03.005","volume":"21","author":"S Lax","year":"2015","unstructured":"Lax, S. & Gilbert, J. A. Hospital-associated microbiota and implications for nosocomial infections. Trends Mol. Med. 21, 427\u2013432 (2015).","journal-title":"Trends Mol. Med."},{"key":"894_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/gm485","volume":"5","author":"RR Miller","year":"2013","unstructured":"Miller, R. R., Montoya, V., Gardy, J. L., Patrick, D. M. & Tang, P. Metagenomics for pathogen detection in public health. Genome Med. 5, 81 (2013).","journal-title":"Genome Med."},{"key":"894_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/srep01413","volume":"3","author":"L Oberauner","year":"2013","unstructured":"Oberauner, L. et al. The ignored diversity: complex bacterial communities in intensive care units revealed by 16S pyrosequencing. Sci. Rep. 3, 1413 (2013).","journal-title":"Sci. Rep."},{"key":"894_CR15","doi-asserted-by":"publisher","first-page":"eaah6500","DOI":"10.1126\/scitranslmed.aah6500","volume":"9","author":"S Lax","year":"2017","unstructured":"Lax, S. et al. Bacterial colonization and succession in a newly opened hospital. Sci. Transl. Med. 9, eaah6500 (2017).","journal-title":"Sci. Transl. Med."},{"key":"894_CR16","doi-asserted-by":"publisher","first-page":"2761","DOI":"10.1128\/JCM.01228-07","volume":"45","author":"JM Janda","year":"2007","unstructured":"Janda, J. M. & Abbott, S. L. 16S rRNA gene sequencing for bacterial identification in the diagnostic laboratory: pluses, perils, and pitfalls. J. Clin. Microbiol. 45, 2761\u20132764 (2007).","journal-title":"J. Clin. Microbiol."},{"key":"894_CR17","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02018-w","volume":"8","author":"B Brooks","year":"2017","unstructured":"Brooks, B. et al. Strain-resolved analysis of hospital rooms and infants reveals overlap between the human and room microbiome. Nat. Commun. 8, 1814 (2017).","journal-title":"Nat. Commun."},{"key":"894_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1299-7","volume":"18","author":"ABR McIntyre","year":"2017","unstructured":"McIntyre, A. B. R. et al. Comprehensive benchmarking and ensemble approaches for metagenomic classifiers. Genome Biol. 18, 182 (2017).","journal-title":"Genome Biol."},{"key":"894_CR19","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1038\/s41587-019-0191-2","volume":"37","author":"D Bertrand","year":"2019","unstructured":"Bertrand, D. et al. Hybrid metagenomic assembly enables high-resolution analysis of resistance determinants and mobile elements in human microbiomes. Nat. Biotechnol. 37, 937\u2013944 (2019).","journal-title":"Nat. Biotechnol."},{"key":"894_CR20","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-019-0663-0","volume":"7","author":"Y Che","year":"2019","unstructured":"Che, Y. et al. Mobile antibiotic resistome in wastewater treatment plants revealed by nanopore metagenomic sequencing. Microbiome 7, 44 (2019).","journal-title":"Microbiome"},{"key":"894_CR21","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1093\/cid\/ciw122","volume":"62","author":"H Kanamori","year":"2016","unstructured":"Kanamori, H., Weber, D. J. & Rutala, W. A. Healthcare outbreaks associated with a water reservoir and infection prevention strategies. Clin. Infect. Dis. 62, 1423\u20131435 (2016).","journal-title":"Clin. Infect. Dis."},{"key":"894_CR22","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/S1473-3099(07)70241-4","volume":"8","author":"SJ Dancer","year":"2008","unstructured":"Dancer, S. J. Importance of the environment in methicillin-resistant Staphylococcus aureus acquisition: the case for hospital cleaning. Lancet Infect. Dis. 8, 101\u2013113 (2008).","journal-title":"Lancet Infect. Dis."},{"key":"894_CR23","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1038\/s41564-018-0202-y","volume":"3","author":"MC de Goffau","year":"2018","unstructured":"de Goffau, M. C. et al. Recognizing the reagent microbiome. Nat. Microbiol. 3, 851\u2013853 (2018).","journal-title":"Nat. Microbiol."},{"key":"894_CR24","first-page":"1","volume":"52","author":"L Sehulster","year":"2003","unstructured":"Sehulster, L. & Chinn, R. Y. Guidelines for environmental infection control in health-care facilities. Recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee (HICPAC). MMWR Recomm. Rep. 52, 1\u201342 (2003).","journal-title":"MMWR Recomm. Rep."},{"key":"894_CR25","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1093\/cid\/cix132","volume":"64","author":"AE Kizny Gordon","year":"2017","unstructured":"Kizny Gordon, A. E. et al. The hospital water environment as a reservoir for carbapenem-resistant organisms causing hospital-acquired infections\u2014a systematic review of the literature. Clin. Infect. Dis. 64, 1435\u20131444 (2017).","journal-title":"Clin. Infect. Dis."},{"key":"894_CR26","doi-asserted-by":"publisher","unstructured":"Danko, D.C. et al. Global genetic cartography of urban metagenomes and anti-microbial resistance. Preprint at bioRxiv https:\/\/doi.org\/10.1101\/724526 (2019).","DOI":"10.1101\/724526"},{"key":"894_CR27","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1111\/ina.12170","volume":"25","author":"C Beggs","year":"2015","unstructured":"Beggs, C., Knibbs, L. D., Johnson, G. R. & Morawska, L. Environmental contamination and hospital-acquired infection: factors that are easily overlooked. Indoor Air 25, 462\u2013474 (2015).","journal-title":"Indoor Air"},{"key":"894_CR28","unstructured":"Ministry of Health Singapore. Guidelines for Control and Prevention of Multi-drug Resistant Organisms (MDROs) in Healthcare Facilities (2013)."},{"key":"894_CR29","doi-asserted-by":"publisher","first-page":"1175","DOI":"10.1038\/s41564-018-0230-7","volume":"3","author":"JYH Lee","year":"2018","unstructured":"Lee, J. Y. H. et al. Global spread of three multidrug-resistant lineages of Staphylococcus epidermidis. Nat. Microbiol. 3, 1175\u20131185 (2018).","journal-title":"Nat. Microbiol."},{"key":"894_CR30","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.mib.2019.06.005","volume":"51","author":"GD Wright","year":"2019","unstructured":"Wright, G. D. Environmental and clinical antibiotic resistomes, same only different. Curr. Opin. Microbiol. 51, 57\u201363 (2019).","journal-title":"Curr. Opin. Microbiol."},{"key":"894_CR31","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.cell.2019.01.001","volume":"176","author":"E Pasolli","year":"2019","unstructured":"Pasolli, E. et al. Extensive unexplored human microbiome diversity revealed by over 150,000 genomes from metagenomes spanning age, geography, and lifestyle. Cell 176, 649\u2013662 (2019).","journal-title":"Cell"},{"key":"894_CR32","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/s41586-019-0965-1","volume":"568","author":"A Almeida","year":"2019","unstructured":"Almeida, A. et al. A new genomic blueprint of the human gut microbiota. Nature 568, 499\u2013504 (2019).","journal-title":"Nature"},{"key":"894_CR33","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1038\/nbt.4229","volume":"36","author":"DH Parks","year":"2018","unstructured":"Parks, D. H. et al. A standardized bacterial taxonomy based on genome phylogeny substantially revises the tree of life. Nat. Biotechnol. 36, 996\u20131004 (2018).","journal-title":"Nat. Biotechnol."},{"key":"894_CR34","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1016\/j.tim.2018.06.007","volume":"26","author":"A San Millan","year":"2018","unstructured":"San Millan, A. Evolution of plasmid-mediated antibiotic resistance in the clinical context. Trends Microbiol. 26, 978\u2013985 (2018).","journal-title":"Trends Microbiol."},{"key":"894_CR35","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1016\/j.tim.2019.02.008","volume":"27","author":"W Calero-Caceres","year":"2019","unstructured":"Calero-Caceres, W., Ye, M. & Balcazar, J. L. Bacteriophages as environmental reservoirs of antibiotic resistance. Trends Microbiol. 27, 570\u2013577 (2019).","journal-title":"Trends Microbiol."},{"key":"894_CR36","doi-asserted-by":"publisher","first-page":"D195","DOI":"10.1093\/nar\/gky1050","volume":"47","author":"V Galata","year":"2019","unstructured":"Galata, V., Fehlmann, T., Backes, C. & Keller, A. PLSDB: a resource of complete bacterial plasmids. Nucleic Acids Res. 47, D195\u2013D202 (2019).","journal-title":"Nucleic Acids Res."},{"key":"894_CR37","doi-asserted-by":"publisher","first-page":"D700","DOI":"10.1093\/nar\/gkx1124","volume":"46","author":"NL Gao","year":"2018","unstructured":"Gao, N. L. et al. MVP: a microbe\u2013phage interaction database. Nucleic Acids Res 46, D700\u2013D707 (2018).","journal-title":"Nucleic Acids Res"},{"key":"894_CR38","doi-asserted-by":"publisher","first-page":"544","DOI":"10.12659\/MSM.890177","volume":"20","author":"N Duran","year":"2014","unstructured":"Duran, N., Temiz, M., Duran, G. G., Eryilmaz, N. & Jenedi, K. Relationship between the resistance genes to quaternary ammonium compounds and antibiotic resistance in staphylococci isolated from surgical site infections. Med. Sci. Monit. 20, 544\u2013550 (2014).","journal-title":"Med. Sci. Monit."},{"key":"894_CR39","doi-asserted-by":"publisher","first-page":"2529","DOI":"10.1056\/NEJMoa1803238","volume":"379","author":"RC Johnson","year":"2018","unstructured":"Johnson, R. C. et al. Investigation of a cluster of Sphingomonas koreensis infections. N. Engl. J. Med. 379, 2529\u20132539 (2018).","journal-title":"N. Engl. J. Med."},{"key":"894_CR40","doi-asserted-by":"crossref","unstructured":"Fahimipour, A.K. et al. Antimicrobial chemicals associate with microbial function and antibiotic resistance indoors. mSystems 3, e00200-18 (2018).","DOI":"10.1128\/mSystems.00200-18"},{"key":"894_CR41","doi-asserted-by":"publisher","first-page":"9807","DOI":"10.1021\/acs.est.6b00262","volume":"50","author":"EM Hartmann","year":"2016","unstructured":"Hartmann, E. M. et al. Antimicrobial chemicals are associated with elevated antibiotic resistance genes in the indoor dust microbiome. Environ. Sci. Technol. 50, 9807\u20139815 (2016).","journal-title":"Environ. Sci. Technol."},{"key":"894_CR42","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1517\/13543780902967624","volume":"18","author":"ME Falagas","year":"2009","unstructured":"Falagas, M. E., Roussos, N., Gkegkes, I. D., Rafailidis, P. I. & Karageorgopoulos, D. E. Fosfomycin for the treatment of infections caused by Gram-positive cocci with advanced antimicrobial drug resistance: a review of microbiological, animal and clinical studies. Expert Opin. Investig. Drugs 18, 921\u2013944 (2009).","journal-title":"Expert Opin. Investig. Drugs"},{"key":"894_CR43","doi-asserted-by":"publisher","first-page":"2732","DOI":"10.1128\/AAC.01768-09","volume":"54","author":"C Urban","year":"2010","unstructured":"Urban, C., Mariano, N. & Rahal, J. J. In vitro double and triple bactericidal activities of doripenem, polymyxin B, and rifampin against multidrug-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Escherichia coli. Antimicrob. Agents Chemother. 54, 2732\u20132734 (2010).","journal-title":"Antimicrob. Agents Chemother."},{"key":"894_CR44","doi-asserted-by":"publisher","first-page":"105","DOI":"10.4103\/2279-042X.162360","volume":"4","author":"M Izadpanah","year":"2015","unstructured":"Izadpanah, M. & Khalili, H. Antibiotic regimens for treatment of infections due to multidrug-resistant Gram-negative pathogens: an evidence-based literature review. J. Res. Pharm. Pract. 4, 105\u2013114 (2015).","journal-title":"J. Res. Pharm. Pract."},{"key":"894_CR45","doi-asserted-by":"publisher","first-page":"3267","DOI":"10.1128\/AAC.45.11.3267-3269.2001","volume":"45","author":"G Werner","year":"2001","unstructured":"Werner, G., Hildebrandt, B. & Witte, W. Aminoglycoside-streptothricin resistance gene cluster aadE\u2013sat4\u2013aphA-3 disseminated among multiresistant isolates of Enterococcus faecium. Antimicrob. Agents Chemother. 45, 3267\u20133269 (2001).","journal-title":"Antimicrob. Agents Chemother."},{"key":"894_CR46","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1111\/j.1749-6632.1957.tb49681.x","volume":"69","author":"L Weinstein","year":"1957","unstructured":"Weinstein, L., Chang, T. W., Hudson, J. B. & Hartl, W. The concurrent use of sulfonamides and antibiotics in the treatment of infections: in vivo and in vitro studies of the effect of sulfonamide-antibiotic combinations on the emergence of drug resistance. Ann. NY Acad. Sci. 69, 408\u2013416 (1957).","journal-title":"Ann. NY Acad. Sci."},{"key":"894_CR47","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1111\/j.1365-294X.1996.tb00299.x","volume":"5","author":"GW Sundin","year":"1996","unstructured":"Sundin, G. W. & Bender, C. L. Dissemination of the strA\u2013strB streptomycin-resistance genes among commensal and pathogenic bacteria from humans, animals, and plants. Mol. Ecol. 5, 133\u2013143 (1996).","journal-title":"Mol. Ecol."},{"key":"894_CR48","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1111\/j.1469-0691.2006.01420.x","volume":"12","author":"S Monecke","year":"2006","unstructured":"Monecke, S. et al. Microarray-based characterisation of a Panton\u2013Valentine leukocidin-positive community-acquired strain of methicillin-resistant Staphylococcus aureus. Clin. Microbiol. Infect. 12, 718\u2013728 (2006).","journal-title":"Clin. Microbiol. Infect."},{"key":"894_CR49","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1016\/S0140-6736(13)61858-9","volume":"382","author":"J Teo","year":"2013","unstructured":"Teo, J. et al. First case of E. anophelis outbreak in an intensive-care unit. Lancet 382, 855\u2013856 (2013).","journal-title":"Lancet"},{"key":"894_CR50","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1017\/S0950268818001966","volume":"146","author":"HL Htun","year":"2018","unstructured":"Htun, H. L. et al. Methicillin-resistant Staphylococcus aureus colonisation: epidemiological and molecular characteristics in an acute-care tertiary hospital in Singapore. Epidemiol. Infect. 146, 1785\u20131792 (2018).","journal-title":"Epidemiol. Infect."},{"key":"894_CR51","doi-asserted-by":"publisher","first-page":"e00264-18","DOI":"10.1128\/genomeA.00264-18","volume":"6","author":"K Nasser","year":"2018","unstructured":"Nasser, K. et al. Draft genome sequences of six multidrug-resistant clinical strains of Acinetobacter baumannii, isolated at two major hospitals in Kuwait. Genome Announc. 6, e00264-18 (2018).","journal-title":"Genome Announc."},{"key":"894_CR52","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/S0195-6701(07)60014-0","volume":"65","author":"JT Walker","year":"2007","unstructured":"Walker, J. T. et al. Hospital and community acquired infection and the built environment\u2014design and testing of infection control rooms. J. Hosp. Infect. 65, 43\u201349 (2007).","journal-title":"J. Hosp. Infect."},{"key":"894_CR53","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1038\/s41591-019-0345-2","volume":"25","author":"JT Ladner","year":"2019","unstructured":"Ladner, J. T., Grubaugh, N. D., Pybus, O. G. & Andersen, K. G. Precision epidemiology for infectious disease control. Nat. Med. 25, 206\u2013211 (2019).","journal-title":"Nat. Med."},{"key":"894_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08864-0","volume":"10","author":"A Mahnert","year":"2019","unstructured":"Mahnert, A. et al. Man-made microbial resistances in built environments. Nat. Commun. 10, 968 (2019).","journal-title":"Nat. Commun."},{"key":"894_CR55","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1086\/588566","volume":"29","author":"ER Goodman","year":"2008","unstructured":"Goodman, E. R. et al. Impact of an environmental cleaning intervention on the presence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci on surfaces in intensive care unit rooms. Infect. Control Hosp. Epidemiol. 29, 593\u2013599 (2008).","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"894_CR56","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1139\/cjm-2018-0275","volume":"65","author":"NA Lerminiaux","year":"2019","unstructured":"Lerminiaux, N. A. & Cameron, A. D. S. Horizontal transfer of antibiotic resistance genes in clinical environments. Can. J. Microbiol. 65, 34\u201344 (2019).","journal-title":"Can. J. Microbiol."},{"key":"894_CR57","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1093\/femsre\/fuy031","volume":"42","author":"MMC Buckner","year":"2018","unstructured":"Buckner, M. M. C., Ciusa, M. L. & Piddock, L. J. V. Strategies to combat antimicrobial resistance: anti-plasmid and plasmid curing. FEMS Microbiol. Rev. 42, 781\u2013804 (2018).","journal-title":"FEMS Microbiol. Rev."},{"key":"894_CR58","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1038\/s41564-019-0492-8","volume":"4","author":"S David","year":"2019","unstructured":"David, S. et al. Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread. Nat. Microbiol. 4, 1919\u20131929 (2019).","journal-title":"Nat. Microbiol."},{"key":"894_CR59","doi-asserted-by":"publisher","first-page":"5693","DOI":"10.1128\/AAC.00761-12","volume":"56","author":"CM Ho","year":"2012","unstructured":"Ho, C. M. et al. High rate of qacA- and qacB-positive methicillin-resistant Staphylococcus aureus isolates from chlorhexidine-impregnated catheter-related bloodstream infections. Antimicrob. Agents Chemother. 56, 5693\u20135697 (2012).","journal-title":"Antimicrob. Agents Chemother."},{"key":"894_CR60","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1017\/ice.2016.174","volume":"37","author":"LM Weiner","year":"2016","unstructured":"Weiner, L. M. et al. Antimicrobial-resistant pathogens associated with healthcare-associated infections: summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2011\u20132014. Infect. Control Hosp. Epidemiol. 37, 1288\u20131301 (2016).","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"894_CR61","doi-asserted-by":"publisher","first-page":"902","DOI":"10.1038\/nmeth.3589","volume":"12","author":"DT Truong","year":"2015","unstructured":"Truong, D. T. et al. MetaPhlAn2 for enhanced metagenomic taxonomic profiling. Nat. Methods 12, 902\u2013903 (2015).","journal-title":"Nat. Methods"},{"key":"894_CR62","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-014-0090-6","volume":"6","author":"M Inouye","year":"2014","unstructured":"Inouye, M. et al. SRST2: rapid genomic surveillance for public health and hospital microbiology labs. Genome Med. 6, 90 (2014).","journal-title":"Genome Med."},{"key":"894_CR63","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2014-15-3-r46","volume":"15","author":"DE Wood","year":"2014","unstructured":"Wood, D. E. & Salzberg, S. L. Kraken: ultrafast metagenomic sequence classification using exact alignments. Genome Biol. 15, r46 (2014).","journal-title":"Genome Biol."},{"key":"894_CR64","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1101\/gr.215087.116","volume":"27","author":"S Koren","year":"2017","unstructured":"Koren, S. et al. Canu: scalable and accurate long-read assembly via adaptive k-mer weighting and repeat separation. Genome Res. 27, 722\u2013736 (2017).","journal-title":"Genome Res."},{"key":"894_CR65","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-5-2-r12","volume":"5","author":"S Kurtz","year":"2004","unstructured":"Kurtz, S. et al. Versatile and open software for comparing large genomes. Genome Biol. 5, r12 (2004).","journal-title":"Genome Biol."},{"key":"894_CR66","doi-asserted-by":"publisher","first-page":"e112963","DOI":"10.1371\/journal.pone.0112963","volume":"9","author":"BJ Walker","year":"2014","unstructured":"Walker, B. J. et al. Pilon: an integrated tool for comprehensive microbial variant detection and genome assembly improvement. PLoS ONE 9, e112963 (2014).","journal-title":"PLoS ONE"},{"key":"894_CR67","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1101\/gr.186072.114","volume":"25","author":"DH Parks","year":"2015","unstructured":"Parks, D. H., Imelfort, M., Skennerton, C. T., Hugenholtz, P. & Tyson, G. W. CheckM: assessing the quality of microbial genomes recovered from isolates, single cells, and metagenomes. Genome Res. 25, 1043\u20131055 (2015).","journal-title":"Genome Res."},{"key":"894_CR68","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0997-x","volume":"17","author":"BD Ondov","year":"2016","unstructured":"Ondov, B. D. et al. Mash: fast genome and metagenome distance estimation using MinHash. Genome Biol. 17, 132 (2016).","journal-title":"Genome Biol."},{"key":"894_CR69","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.12688\/f1000research.19675.1","volume":"8","author":"NT Pierce","year":"2019","unstructured":"Pierce, N. T., Irber, L., Reiter, T., Brooks, P. & Brown, C. T. Large-scale sequence comparisons with sourmash. F1000Res 8, 1006 (2019).","journal-title":"F1000Res"},{"key":"894_CR70","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1128\/AAC.01310-13","volume":"58","author":"SK Gupta","year":"2014","unstructured":"Gupta, S. K. et al. ARG-ANNOT, a new bioinformatic tool to discover antibiotic resistance genes in bacterial genomes. Antimicrob. Agents Chemother. 58, 212\u2013220 (2014).","journal-title":"Antimicrob. Agents Chemother."},{"key":"894_CR71","doi-asserted-by":"publisher","first-page":"D581","DOI":"10.1093\/nar\/gkt1099","volume":"42","author":"AR Wattam","year":"2014","unstructured":"Wattam, A. R. et al. PATRIC, the bacterial bioinformatics database and analysis resource. Nucleic Acids Res. 42, D581\u2013D591 (2014).","journal-title":"Nucleic Acids Res."},{"key":"894_CR72","doi-asserted-by":"publisher","first-page":"e985","DOI":"10.7717\/peerj.985","volume":"3","author":"S Roux","year":"2015","unstructured":"Roux, S., Enault, F., Hurwitz, B. L. & Sullivan, M. B. VirSorter: mining viral signal from microbial genomic data. PeerJ 3, e985 (2015).","journal-title":"PeerJ"},{"key":"894_CR73","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-9-75","volume":"9","author":"RK Aziz","year":"2008","unstructured":"Aziz, R. K. et al. The RAST Server: rapid annotations using subsystems technology. BMC Genomics 9, 75 (2008).","journal-title":"BMC Genomics"},{"key":"894_CR74","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-0951-y","volume":"17","author":"S Gao","year":"2016","unstructured":"Gao, S., Bertrand, D., Chia, B. K. & Nagarajan, N. OPERA-LG: efficient and exact scaffolding of large, repeat-rich eukaryotic genomes with performance guarantees. Genome Biol. 17, 102 (2016).","journal-title":"Genome Biol."},{"key":"894_CR75","doi-asserted-by":"crossref","unstructured":"Gao, S., Bertrand, D., & Nagarajan, N. FinIS: improved in silico finishing using an exact quadratic programming formulation. In Algorithms in Bioinformatics (Eds. Raphael, B. & Tang, J.) 314\u2013325 (Springer, 2012).","DOI":"10.1007\/978-3-642-33122-0_25"},{"key":"894_CR76","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0524-x","volume":"15","author":"TJ Treangen","year":"2014","unstructured":"Treangen, T. J., Ondov, B. D., Koren, S. & Phillippy, A. M. The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes. Genome Biol. 15, 524 (2014).","journal-title":"Genome Biol."},{"key":"894_CR77","doi-asserted-by":"publisher","first-page":"2665","DOI":"10.1534\/genetics.105.048975","volume":"172","author":"TC Bruen","year":"2006","unstructured":"Bruen, T. C., Philippe, H. & Bryant, D. A simple and robust statistical test for detecting the presence of recombination. Genetics 172, 2665\u20132681 (2006).","journal-title":"Genetics"},{"key":"894_CR78","doi-asserted-by":"publisher","first-page":"e9490","DOI":"10.1371\/journal.pone.0009490","volume":"5","author":"MN Price","year":"2010","unstructured":"Price, M. N., Dehal, P. S. & Arkin, A. P. FastTree 2\u2014approximately maximum-likelihood trees for large alignments. PLoS ONE 5, e9490 (2010).","journal-title":"PLoS ONE"},{"key":"894_CR79","doi-asserted-by":"publisher","first-page":"3041","DOI":"10.1093\/molbev\/msy194","volume":"35","author":"G Yu","year":"2018","unstructured":"Yu, G., Lam, T. T., Zhu, H. & Guan, Y. Two methods for mapping and visualizing associated data on phylogeny using ggtree. Mol. Biol. Evol. 35, 3041\u20133043 (2018).","journal-title":"Mol. Biol. Evol."},{"key":"894_CR80","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1111\/2041-210X.12613","volume":"7","author":"TC Hsieh","year":"2016","unstructured":"Hsieh, T. C., Ma, K. H. & Chao, A. iNEXT: an R package for rarefaction and extrapolation of species diversity (Hill numbers). Methods Ecol. Evol. 7, 1451\u20131456 (2016).","journal-title":"Methods Ecol. Evol."}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41591-020-0894-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41591-020-0894-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41591-020-0894-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T18:03:08Z","timestamp":1684605788000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-020-0894-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6]]},"references-count":80,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["894"],"URL":"https:\/\/doi.org\/10.1038\/s41591-020-0894-4","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/644740","asserted-by":"object"}]},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6]]},"assertion":[{"value":"20 May 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 April 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 June 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}