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Title: Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment

Abstract

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 (>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 (>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.

Authors:
 [1]; ORCiD logo [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [2];  [3];  [1];  [1];  [4]; ORCiD logo [1];  [1]; ORCiD logo [5];  [6]; ORCiD logo [7];  [8] more »; ORCiD logo [9] « less
  1. Genome Inst. of Singapore (Singapore)
  2. Singapore Univ. of Technology and Design (Singapore)
  3. Singapore General Hospital (Singapore); National Univ. of Singapore (Singapore). Graduate Medical School
  4. National Univ. Hospital (Singapore)
  5. Cornell Univ., Ithaca, NY (United States). Weill Medical College
  6. National Centre for Infectious Diseases (Singapore); Tan Tock Seng Hospital (Singapore); Nanyang Technological Univ. (Singapore)
  7. National Centre for Infectious Diseases (Singapore); Tan Tock Seng Hospital (Singapore); National Univ. of Singapore (Singapore)
  8. National Centre for Infectious Diseases (Singapore); Tan Tock Seng Hospital (Singapore)
  9. Genome Inst. of Singapore (Singapore); National Univ. of Singapore (Singapore)
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC); US Naval Medical Research Center (NMRC); WorldQuant Foundation; Bill and Melinda Gates Foundation; Alfred P. Sloan Foundation
Contributing Org.:
MetaSUB Consortium
OSTI Identifier:
1766495
Grant/Contract Number:  
AC02-05CH11231; CGAug16C005; OPP1151054; G-2015-13964
Resource Type:
Accepted Manuscript
Journal Name:
Nature Medicine
Additional Journal Information:
Journal Volume: 26; Journal Issue: 6; Journal ID: ISSN 1078-8956
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Chng, Kern Rei, Li, Chenhao, Bertrand, Denis, Ng, Amanda Hui Qi, Kwah, Junmei Samantha, Low, Hwee Meng, Tong, Chengxuan, Natrajan, Maanasa, Zhang, Michael Hongjie, Xu, Licheng, Ko, Karrie Kwan Ki, Ho, Eliza Xin Pei, Av-Shalom, Tamar V., Teo, Jeanette Woon Pei, Khor, Chiea Chuen, Chen, Swaine L., Mason, Christopher E., Ng, Oon Tek, Marimuthu, Kalisvar, Ang, Brenda, and Nagarajan, Niranjan. Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment. United States: N. p., 2020. Web. doi:10.1038/s41591-020-0894-4.
Chng, Kern Rei, Li, Chenhao, Bertrand, Denis, Ng, Amanda Hui Qi, Kwah, Junmei Samantha, Low, Hwee Meng, Tong, Chengxuan, Natrajan, Maanasa, Zhang, Michael Hongjie, Xu, Licheng, Ko, Karrie Kwan Ki, Ho, Eliza Xin Pei, Av-Shalom, Tamar V., Teo, Jeanette Woon Pei, Khor, Chiea Chuen, Chen, Swaine L., Mason, Christopher E., Ng, Oon Tek, Marimuthu, Kalisvar, Ang, Brenda, & Nagarajan, Niranjan. Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment. United States. https://doi.org/10.1038/s41591-020-0894-4
Chng, Kern Rei, Li, Chenhao, Bertrand, Denis, Ng, Amanda Hui Qi, Kwah, Junmei Samantha, Low, Hwee Meng, Tong, Chengxuan, Natrajan, Maanasa, Zhang, Michael Hongjie, Xu, Licheng, Ko, Karrie Kwan Ki, Ho, Eliza Xin Pei, Av-Shalom, Tamar V., Teo, Jeanette Woon Pei, Khor, Chiea Chuen, Chen, Swaine L., Mason, Christopher E., Ng, Oon Tek, Marimuthu, Kalisvar, Ang, Brenda, and Nagarajan, Niranjan. Mon . "Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment". United States. https://doi.org/10.1038/s41591-020-0894-4. https://www.osti.gov/servlets/purl/1766495.
@article{osti_1766495,
title = {Cartography of opportunistic pathogens and antibiotic resistance genes in a tertiary hospital environment},
author = {Chng, Kern Rei and Li, Chenhao and Bertrand, Denis and Ng, Amanda Hui Qi and Kwah, Junmei Samantha and Low, Hwee Meng and Tong, Chengxuan and Natrajan, Maanasa and Zhang, Michael Hongjie and Xu, Licheng and Ko, Karrie Kwan Ki and Ho, Eliza Xin Pei and Av-Shalom, Tamar V. and Teo, Jeanette Woon Pei and Khor, Chiea Chuen and Chen, Swaine L. and Mason, Christopher E. and Ng, Oon Tek and Marimuthu, Kalisvar and Ang, Brenda and Nagarajan, Niranjan},
abstractNote = {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 (>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 (>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.},
doi = {10.1038/s41591-020-0894-4},
journal = {Nature Medicine},
number = 6,
volume = 26,
place = {United States},
year = {Mon Jun 08 00:00:00 EDT 2020},
month = {Mon Jun 08 00:00:00 EDT 2020}
}

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Low‐intensity management benefits solitary bees in olive groves
journal, October 2019

  • Martínez‐Núñez, Carlos; Manzaneda, Antonio J.; Isla, Jorge
  • Journal of Applied Ecology, Vol. 57, Issue 1
  • DOI: 10.1111/1365-2664.13511

Exotic eucalypts: From demonized trees to allies of tropical forest restoration?
journal, October 2019

  • Brancalion, Pedro H. S.; Amazonas, Nino T.; Chazdon, Robin L.
  • Journal of Applied Ecology, Vol. 57, Issue 1
  • DOI: 10.1111/1365-2664.13513

Bacterial colonization of minerals in grassland soils is selective and highly dynamic
journal, August 2019

  • Vieira, Selma; Sikorski, Johannes; Gebala, Aurelia
  • Environmental Microbiology, Vol. 22, Issue 3
  • DOI: 10.1111/1462-2920.14751

Environmental DNA analysis shows high potential as a tool for estimating intraspecific genetic diversity in a wild fish population
journal, May 2020

  • Tsuji, Satsuki; Maruyama, Atsushi; Miya, Masaki
  • Molecular Ecology Resources, Vol. 20, Issue 5
  • DOI: 10.1111/1755-0998.13165

How should we estimate diversity in the fossil record? Testing richness estimators using sampling‐standardised discovery curves
journal, March 2018

  • Close, Roger A.; Evers, Serjoscha W.; Alroy, John
  • Methods in Ecology and Evolution, Vol. 9, Issue 6
  • DOI: 10.1111/2041-210x.12987

The r package divDyn for quantifying diversity dynamics using fossil sampling data
journal, March 2019

  • Kocsis, Ádám T.; Reddin, Carl J.; Alroy, John
  • Methods in Ecology and Evolution, Vol. 10, Issue 5
  • DOI: 10.1111/2041-210x.13161

Choices of sampling method bias functional components estimation and ability to discriminate assembly mechanisms
journal, April 2019


Surveying tropical birds is much harder than you think: a primer of best practices
journal, October 2018

  • Robinson, W. Douglas; Lees, Alexander C.; Blake, John G.
  • Biotropica, Vol. 50, Issue 6
  • DOI: 10.1111/btp.12608

Canopy tree preference by insectivorous birds in shade‐coffee farms: Implications for migratory bird conservation
journal, March 2019

  • Narango, Desirée L.; Tallamy, Douglas W.; Snyder, Kerry J.
  • Biotropica, Vol. 51, Issue 3
  • DOI: 10.1111/btp.12642

Temporal variation in the influence of forest succession on caterpillar communities: A long‐term study in a tropical dry forest 
journal, May 2019

  • Boege, Karina; Villa‐Galaviz, Edith; López‐Carretero, Antonio
  • Biotropica, Vol. 51, Issue 4
  • DOI: 10.1111/btp.12666

Quantifying regional biodiversity in the tropics: A case study of freshwater fish in Trinidad and Tobago
journal, August 2019

  • Jones, Faith A. M.; Rutherford, Mike G.; Deacon, Amy E.
  • Biotropica, Vol. 51, Issue 5
  • DOI: 10.1111/btp.12692

Elevational filtering and the evolution of planthoppers (Hemiptera, Fulgoromorpha) in Papua New Guinea
journal, March 2020

  • Chatelain, Paul; Le Cesne, Maxime; Elias, Marianne
  • Biotropica, Vol. 52, Issue 2
  • DOI: 10.1111/btp.12710

Linking dung beetle‐mediated functions to interactions in the Atlantic Forest: Sampling design matters
journal, March 2020

  • Raine, Elizabeth H.; Mikich, Sandra B.; Lewis, Owen T.
  • Biotropica, Vol. 52, Issue 2
  • DOI: 10.1111/btp.12722

Interpreting beta‐diversity components over time to conserve metacommunities in highly dynamic ecosystems
journal, May 2017

  • Ruhí, Albert; Datry, Thibault; Sabo, John L.
  • Conservation Biology, Vol. 31, Issue 6
  • DOI: 10.1111/cobi.12906

Recreational freshwater fishing drives non-native aquatic species richness patterns at a continental scale
journal, April 2017

  • Davis, A. J. S.; Darling, J. A.
  • Diversity and Distributions, Vol. 23, Issue 6
  • DOI: 10.1111/ddi.12557

Turnover and nestedness in subtropical dung beetle assemblages along an elevational gradient
journal, April 2018

  • da Silva, Pedro G.; Lobo, Jorge M.; Hensen, Maristela C.
  • Diversity and Distributions, Vol. 24, Issue 9
  • DOI: 10.1111/ddi.12763

Bees use anthropogenic habitats despite strong natural habitat preferences
journal, February 2019

  • Collado, Miguel Á.; Sol, Daniel; Bartomeus, Ignasi
  • Diversity and Distributions, Vol. 25, Issue 6
  • DOI: 10.1111/ddi.12899

The biodiversity benefit of native forests and mixed‐species plantations over monoculture plantations
journal, August 2019

  • Wang, Xiaoyang; Hua, Fangyuan; Wang, Lin
  • Diversity and Distributions, Vol. 25, Issue 11
  • DOI: 10.1111/ddi.12972

Differential temporal beta‐diversity patterns of native and non‐native arthropod species in a fragmented native forest landscape
journal, July 2018

  • Matthews, Thomas J.; Sadler, Jon; Carvalho, Rui
  • Ecography, Vol. 42, Issue 1
  • DOI: 10.1111/ecog.03812

Sampling design may obscure species–area relationships in landscape‐scale field studies
journal, October 2019

  • Bueno, Anderson Saldanha; Masseli, Gabriel S.; Kaefer, Igor L.
  • Ecography, Vol. 43, Issue 1
  • DOI: 10.1111/ecog.04568

Comparative responses of termite functional and taxonomic diversity to land‐use change
journal, May 2019

  • Liu, Shengjie; Lin, Xiaobing; Behm, Jocelyn E.
  • Ecological Entomology, Vol. 44, Issue 6
  • DOI: 10.1111/een.12755

Anthropogenic disturbance equalizes diversity levels in arbuscular mycorrhizal fungal communities
journal, April 2018

  • García de León, David; Davison, John; Moora, Mari
  • Global Change Biology, Vol. 24, Issue 6
  • DOI: 10.1111/gcb.14131

Trade‐offs between carbon stocks and biodiversity in European temperate forests
journal, November 2018

  • Sabatini, Francesco Maria; de Andrade, Rafael Barreto; Paillet, Yoan
  • Global Change Biology, Vol. 25, Issue 2
  • DOI: 10.1111/gcb.14503

Congruence across taxa and spatial scales: Are we asking too much of species data?
journal, August 2018

  • Burrascano, S.; de Andrade, R. B.; Paillet, Y.
  • Global Ecology and Biogeography, Vol. 27, Issue 8
  • DOI: 10.1111/geb.12766

Body size, reef area and temperature predict global reef‐fish species richness across spatial scales
journal, December 2018

  • Barneche, D. R.; Rezende, E. L.; Parravicini, V.
  • Global Ecology and Biogeography, Vol. 28, Issue 3
  • DOI: 10.1111/geb.12851

The acoustic ecology of an Amazonian bird assemblage: the role of allometry, competition and environmental filtering in the acoustic structure
journal, March 2019

  • Torres, Ingrid M. D.; Barreiros, Marcelo H. M.; de Araújo, Carlos B.
  • Ibis, Vol. 162, Issue 3
  • DOI: 10.1111/ibi.12720

Livestock areas with canopy cover sustain dung beetle diversity in the humid subtropical Chaco forest
journal, January 2019

  • Guerra Alonso, Celeste Beatriz; Zurita, Gustavo A.; Bellocq, M. Isabel
  • Insect Conservation and Diversity, Vol. 12, Issue 4
  • DOI: 10.1111/icad.12340

A cross-continental comparison of assemblages of seed- and fruit-feeding insects in tropical rain forests: Faunal composition and rates of attack
journal, March 2018

  • Basset, Yves; Dahl, Chris; Ctvrtecka, Richard
  • Journal of Biogeography, Vol. 45, Issue 6
  • DOI: 10.1111/jbi.13211

Model averaging fails to improve the extrapolation capability of the island species–area relationship
journal, June 2019

  • Matthews, Thomas J.; Aspin, Thomas W. H.
  • Journal of Biogeography
  • DOI: 10.1111/jbi.13598

Genotypic diversity in root-endophytic fungi reflects efficient dispersal and environmental adaptation
journal, August 2017

  • Glynou, Kyriaki; Ali, Tahir; Kia, Sevda Haghi
  • Molecular Ecology, Vol. 26, Issue 18
  • DOI: 10.1111/mec.14231

Non‐random association patterns in a plant–mycorrhizal fungal network reveal host–symbiont specificity
journal, May 2018

  • Sepp, Siim‐Kaarel; Davison, John; Jairus, Teele
  • Molecular Ecology, Vol. 28, Issue 2
  • DOI: 10.1111/mec.14924

Historical biome distribution and recent human disturbance shape the diversity of arbuscular mycorrhizal fungi
journal, July 2017

  • Pärtel, Meelis; Öpik, Maarja; Moora, Mari
  • New Phytologist, Vol. 216, Issue 1
  • DOI: 10.1111/nph.14695

Forest biomass, soil and biodiversity relationships originate from biogeographic affinity and direct ecological effects
journal, July 2019

  • Noreika, Norbertas; Helm, Aveliina; Öpik, Maarja
  • Oikos, Vol. 128, Issue 11
  • DOI: 10.1111/oik.06693

Reconciling biodiversity and carbon stock conservation in an Afrotropical forest landscape
journal, March 2018

  • Van de Perre, Frederik; Willig, Michael R.; Presley, Steven J.
  • Science Advances, Vol. 4, Issue 3
  • DOI: 10.1126/sciadv.aar6603

High Rate of Infection by Only Oncogenic Human Papillomavirus in Amerindians
journal, June 2018


Vascular Epiphytic Diversity in a Neotropical Transition Zone Is Driven by Environmental and Structural Heterogeneity
journal, January 2019

  • de la Rosa-Manzano, Edilia; Mendieta-Leiva, Glenda; Guerra-Pérez, Antonio
  • Tropical Conservation Science, Vol. 12
  • DOI: 10.1177/1940082919882203

Probing the Rare Biosphere of the North-West Mediterranean Sea: An Experiment with High Sequencing Effort
journal, July 2016


The menu varies with metabarcoding practices: A case study with the bat Plecotus auritus
journal, July 2019


Successional, spatial, and seasonal changes in seed rain in the Atlantic forest of southern Bahia, Brazil
journal, December 2019


Simple does not mean poor: grasslands and forests harbor similar ant species richness and distinct composition in highlands of southern Brazil
journal, January 2018


Cervicovaginal Fungi and Bacteria Associated With Cervical Intraepithelial Neoplasia and High-Risk Human Papillomavirus Infections in a Hispanic Population
journal, October 2018

  • Godoy-Vitorino, Filipa; Romaguera, Josefina; Zhao, Chunyu
  • Frontiers in Microbiology, Vol. 9
  • DOI: 10.3389/fmicb.2018.02533

Comparative Analysis of Intestine Microbiota of Four Wild Waterbird Species
journal, August 2019


Antibiotic-Induced Perturbations Are Manifested in the Dominant Intestinal Bacterial Phyla of Atlantic Salmon
journal, August 2019


Relationship between Wetland Plant Communities and Environmental Factors in the Tumen River Basin in Northeast China
journal, March 2019

  • Zheng, Xiaojun; Fu, Jing; Ramamonjisoa, Noelikanto
  • Sustainability, Vol. 11, Issue 6
  • DOI: 10.3390/su11061559

A meta-barcoding census of freshwater planktonic protists in Appalachia – Natural Tunnel State Park, Virginia, USA
journal, October 2018

  • Cahoon, A. Bruce; Huffman, Ashley G.; Krager, Megan M.
  • Metabarcoding and Metagenomics, Vol. 2
  • DOI: 10.3897/mbmg.2.26939

Phage-centric ecological interactions in aquatic ecosystems revealed through ultra-deep metagenomics
text, January 2019

  • Kavagutti, Vinicius S.; Andrei, Adrian-Ştefan; Mehrshad, Maliheh
  • BioMed Central
  • DOI: 10.5167/uzh-183761

Variegated tropical landscapes conserve diverse dung beetle communities
journal, January 2017

  • Costa, Cristiane; Oliveira, Victor Hugo F.; Maciel, Rafaella
  • PeerJ, Vol. 5
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Nectar-living yeasts of a tropical host plant community: diversity and effects on community-wide floral nectar traits
journal, January 2017

  • Canto, Azucena; Herrera, Carlos M.; Rodriguez, Rosalina
  • PeerJ, Vol. 5
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Genomic Characterization of Extensively Drug-Resistant NDM-Producing Acinetobacter baumannii Clinical Isolates With the Emergence of Novel blaADC-257
journal, November 2021

  • Zafer, Mai M.; Hussein, Amira F. A.; Al-Agamy, Mohamed H.
  • Frontiers in Microbiology, Vol. 12
  • DOI: 10.3389/fmicb.2021.736982