Abstract
Antimicrobial resistance is a public health threat associated with increased morbidity, mortality and financial burden in nursing homes and other healthcare settings1. Residents of nursing homes are at increased risk of pathogen colonization and infection owing to antimicrobial-resistant bacteria and fungi. Nursing homes act as reservoirs, amplifiers and disseminators of antimicrobial resistance in healthcare networks and across geographical regions2. Here we investigate the genomic epidemiology of the emerging, multidrug-resistant human fungal pathogen Candida auris in a ventilator-capable nursing home. Coupling strain-resolved metagenomics with isolate sequencing, we report skin colonization and clonal spread of C. auris on the skin of nursing home residents and throughout a metropolitan region. We also report that most Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Entobacter species (ESKAPE) pathogens and other high-priority pathogens (including Escherichia coli, Providencia stuartii, Proteus mirabilis and Morganella morganii) are shared in a nursing home. Integrating microbiome and clinical microbiology data, we detect carbapenemase genes at multiple skin sites on residents identified as carriers of these genes. We analyse publicly available shotgun metagenomic samples (stool and skin) collected from residents with varying medical conditions living in seven other nursing homes and provide additional evidence of previously unappreciated bacterial strain sharing. Taken together, our data suggest that skin is a reservoir for colonization by C. auris and ESKAPE pathogens and their associated antimicrobial-resistance genes.
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Fig. 1: Recovery of C. auris, ESKAPE and predominant bacterial MAGs from residents of nursing homes.
Fig. 2: Skin of nursing home residents is a reservoir for C. auris, ESKAPE pathogens and antimicrobial-resistance genes.
Fig. 3: Skin of nursing home residents is a potential reservoir for bacterial and fungal strain sharing.
Fig. 4: Regional spread, personalized diversification and sharing of C. auris among nursing home residents.
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Data availability
Shotgun metagenome data generated in this study are available under NCBI BioProject accession PRJNA672955. As the study was conducted with a waiver of informed consent, we performed a secondary screen to ensure that human reads were depleted from the samples before deposition into the SRA. This was done by first mapping ‘human-depleted’ reads to RefSeq using Kraken, followed by mapping unclassified reads to the MAG catalogue. Only reads that mapped positively to a microbial genome were deposited into the SRA. The following publicly available shotgun data were included: SRR9674474–SRR9674617, SRR13789152–SRR13789154, SRR13789165, SRR13789176, SRR13789187, SRR13789197–SRR13789230, SRR13789240, SRR13789258, SRR13789269, SRR13789280–SRR13789306, SRR13789317, SRR13789324–SRR13789351, SRR13789356, SRR13789367, SRR13789378, SRR13789380–SRR13789491, SRR13789493, SRR13789504, SRR13789515, SRR13789520–SRR13789566, SRR13789571, SRR13789582, SRR13789593–SRR13789622, SRR13789633, SRR13789644, SRR13789651–SRR13789660, SRR13789662–SRR13789671, SRR13789673–SRR13789678, SRR13789687, SRR13789698, SRR13789707–SRR13789734, SRR13789737, SRR13789748, SRR13789759, SRR13789770, SRR13789771, SRR13789782, SRR13789793, SRR13789804, SRR13789815, SRR13789819–SRR13789845, SRR13789856, SRR13789867, SRR13789878, SRR13789881–SRR13789908, SRR13789917, SRR13789918, SRR13789929, SRR13789940, SRR13789951, SRR13789962, SRR13789965–SRR13790022, SRR13790032, SRR13790043, SRR13790054, SRR13790065, SRR13790076–SRR13790104, SRR13790115, SRR13790126, SRR13790133–SRR13790142, SRR13789279, SRR13789567–SRR13789570, SRR13789572–SRR13789581, SRR13789583–SRR13789592, SRR13789623–SRR13789632, SRR13789634–SRR13789643, SRR13789645–SRR13789650, SRR13790023–SRR13790031, SRR13790033–SRR13790042, SRR13790044–SRR13790053, SRR13790055–SRR13790064, SRR13790066–SRR13790075, SRR13790105–SRR13790114, SRR13790116–SRR13790125, SRR13790127–SRR13790132, ERR4043872, ERR4043875, ERR4043886, ERR4043889, ERR4043922, ERR4043925, ERR4043935, ERR4043938, ERR4043956, ERR4043959, ERR4045305–ERR4045326, SRR13725807–SRR13725809, SRR13725814–SRR13725820, SRR13725822, SRR13725823, SRR13725829, SRR13725840–SRR13725842, SRR13725844–SRR13725853, SRR13725855–SRR13725859, SRR13725811–SRR13725813, SRR13725824,–SRR13725828, SRR13725830, SRR13725831, SRR13725833–SRR13725839, SRR9040400–SRR9040477, SRR9611076, SRR13725744, SRR13725780, SRR13725883, SRR13725920, SRR13725952, SRR13725992, SRR13726011, SRR13726018, SRR13726028, SRR13726047, SRR13726057, SRR13726066, SRR13726075, SRR13726085, SRR13789146, SRR13789147–SRR13789151, SRR13789155–SRR13789164, SRR13789166–SRR13789175, SRR13789177–SRR13789186, SRR13789188–SRR13789196, SRR13789251–SRR13789257, SRR13789259–SRR13789268, SRR13789270–SRR13789278, SRR13789492, SRR13789494–SRR13789503, SRR13789505–SRR13789514, SRR13789516–SRR13789519, SRR13789679–SRR13789686, SRR13789688–SRR13789706, SRR13789735, SRR13789736, SRR13789738–SRR13789747, SRR13789749–SRR13789758, SRR13789760–SRR13789769, SRR13789772–SRR13789781, SRR13789783–SRR13789792, SRR13789794–SRR13789803, SRR13789805–SRR13789814, SRR13789816–SRR13789818, SRR13789846–SRR13789855, SRR13789857–SRR13789866, SRR13789868–SRR13789877, SRR13789879, SRR13789880, SRR13789909–SRR13789916, SRR13789919–SRR13789928, SRR13789930–SRR13789939, SRR13789941–SRR13789950, SRR13789952–SRR13789961, SRR13789963, SRR13789964, SRR13725737, SRR13725739–SRR13725743, SRR13725745–SRR13725747, SRR13725749–SRR13725758, SRR13725760–SRR13725769, SRR13725771–SRR13725779, SRR13725864, SRR13725867–SRR13725876, SRR13725878–SRR13725882, SRR13725903–SRR13725909, SRR13725911–SRR13725919, SRR13725935–SRR13725942, SRR13725944–SRR13725951, SRR13725973–SRR13725975, SRR13725978–SRR13725987, SRR13725989–SRR13725991, SRR13725993–SRR13725998, SRR13726000–SRR13726009, SRR13726012–SRR13726014, SRR13726016, SRR13726017, SRR13726019, SRR13726020, SRR13726022–SRR13726027, SRR13726029–SRR13726031, SRR13726033–SRR13726042, SRR13726044–SRR13726046, SRR13726048–SRR13726053, SRR13726055, SRR13726056, SRR13726058–SRR13726064, SRR13726067–SRR13726074, SRR13726077–SRR13726084, SRR13726086, SRR13789231–SRR13789239, SRR13789241–SRR13789250, SRR13789313–SRR13789316, SRR13789318–SRR13789323, SRR13789352–SRR13789355, SRR13789357–SRR13789366, SRR13789368–SRR13789377, SRR13789379, SRR13725748, SRR13725759, SRR13725770, SRR13725781, SRR13725792, SRR13725802, SRR13725860–SRR13725863, SRR13725866, SRR13725884–SRR13725887, SRR13725889–SRR13725898, SRR13725900–SRR13725902, SRR13725922–SRR13725931, SRR13725933, SRR13725934, SRR13725943, SRR13725953–SRR13725972, SRR13725976, SRR13725977, SRR13725988, SRR13725999, SRR13726010, SRR13726015, SRR13726021, SRR13726032, SRR13726043, SRR13726054, SRR13726065, SRR13726076, SRR13726087–SRR13726089, SRR13789307–SRR13789312, SRR13725738, SRR13725782–SRR13725791, SRR13725793–SRR13725801, SRR13725803–SRR13725806, SRR13725810, SRR13725821, SRR13725832, SRR13725843, SRR13725854, SRR13725865, SRR13725877, SRR13725888, SRR13725899, SRR13725910, SRR13725921, SRR13725932, SRR8797655–SRR8797950, SAMN11269715–SAMN11270010, SRR13789661 and SRR13789672. The following publicly available C. auris genomes were included: SAMN10139226, SAMN10139227, SAMN10139260, SAMN10139351, SAMN10139373, SAMN10139374, SAMN10139498–SAMN10139501, SAMN10139511–SAMN10139513, SAMN10139526, SAMN10139527, SAMN10139534–SAMN10139548, SAMN10139551, SAMN10139552, SAMN14925561, SAMN15689540, SAMN15689542–SAMN15689547, SAMN15689549, SAMN15689550, SAMN15689552–SAMN15689564 and SRR12363157. Source data are provided with this paper.
Code availability
All data and code used to reproduce our analyses are available at GitHub (https://github.com/skinmicrobiome/ESKAPE).
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Acknowledgements
This study was supported by the Intramural Research Programs of the National Institutes of Health (NIH) National Human Genome Research Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, by CDC contract number 75D30118C02900 and by CDC cooperative agreement number U54CK000607. This study used the computational resources of the NIH HPC Biowulf Cluster (http://hpc.nih.gov). J.A.S. is an Associate Fellow of the Canadian Institute for Advanced Research (CIFAR) programme Fungal Kingdom: Threats & Opportunities. We thank M. Park for generating nanopore genome assemblies; A. Litvintseva for sharing C. auris isolates; J. Lichtenberg and C. Worby for insightful meetings; S. Huang, V. Young, P. Thomas and A. Litvintseva for their critical reading of the manuscript, which improved the text; and the authors of studies who made their data publicly available and other members of the Segre and Kong laboratories, especially J. Han, A. Amirkhani and Q. Chen for underlying efforts, and the developers of the bioinformatics tools and packages used in this work.
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Author notes
Diana M. Proctor
Present address: Department of Microbiology and Molecular Genetics, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA
Ryan A. Blaustein
Present address: Department of Nutrition and Food Science, University of Maryland, College Park, MD, USA
Thomas K. Atkins
Present address: Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA
These authors contributed equally: Mary K. Hayden, Julia A. Segre
Authors and Affiliations
Microbial Genomics Section, Translational and Functional Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA
Diana M. Proctor, Clay Deming, Sean Conlan, Ryan A. Blaustein, Thomas K. Atkins & Julia A. Segre
Department of Internal Medicine, Division of Infectious Diseases, Rush University Medical Center, Chicago, IL, USA
Sarah E. Sansom, Thelma Dangana, Christine Fukuda, Lahari Thotapalli, Michael Y. Lin & Mary K. Hayden
Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA
Heidi H. Kong
NIH Intramural Sequencing Center, National Human Genome Research Institute, National Institutes of Health, Rockville, MD, USA
Jim Mullikin, Jim Thomas, Alice Young, Gerry Bouffard, Betty Barnabas, Shelise Brooks, Joel Han, Chlöe Buchter, Shi-ling Ho, Juyun Crawford, Richelle Legaspi, Quino Maduro, Holly Marfani, Casandra Montemayor, Nancy Riebow, Karen Schandler, Brian Schmidt, Christina Sison, Mal Stantripop, Sean Black, Mila Dekhtyar, Cathy Masiello, Jenny McDowell, Morgan Park, Pam Thomas & Meg Vemulapalli
Authors
Diana M. Proctor
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2. Sarah E. Sansom
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3. Clay Deming
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8. Christine Fukuda
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9. Lahari Thotapalli
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10. Heidi H. Kong
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11. Michael Y. Lin
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Consortia
NISC Comparative Sequencing Program
Jim Mullikin
, Jim Thomas
, Alice Young
, Gerry Bouffard
, Betty Barnabas
, Shelise Brooks
, Joel Han
, Chlöe Buchter
, Shi-ling Ho
, Juyun Crawford
, Richelle Legaspi
, Quino Maduro
, Holly Marfani
, Casandra Montemayor
, Nancy Riebow
, Karen Schandler
, Brian Schmidt
, Christina Sison
, Mal Stantripop
, Sean Black
, Mila Dekhtyar
, Cathy Masiello
, Jenny McDowell
, Morgan Park
, Pam Thomas
& Meg Vemulapalli
Contributions
Conceptualization: D.M.P., M.Y.L., M.K.H., H.H.K. and J.A.S. Data curation: D.M.P., S.E.S., S.C., T.D., C.F. and L.H. Formal analyses: D.M.P., S.E.S., S.C. and L.T. Investigation: D.M.P., S.E.S., C.D., S.C., T.K.A., T.D. and M.Y.L. Methodology: D.M.P., S.C., R.A.B., C.D., M.Y.L., M.K.H. and J.A.S. Software: D.M.P. and R.A.B. Funding acquisition: J.A.S. and M.K.H. Project administration: H.H.K., M.K.H. and J.A.S. Supervision: J.A.S. and M.K.H. Resources: J.A.S. and M.K.H. Visualization: D.M.P. Writing original draft: D.M.P., S.E.S., M.K.H. and J.A.S. Writing, reviewing and editing: D.M.P., S.E.S., M.K.H. and J.A.S. All authors approved the final manuscript. NISC Comparative Sequencing Program author contributions: data curation: J. Mullikin, J.T., A.Y., G.B., B.B., S. Brooks, J.H., S-l.H., C.B., J.C., R.L., Q.M., H.M., C. Montemayor, N.R., K.S., B.S., C.S., M.S., S. Black, M.D., C. Masiello, J. McDowell, M.P., P.T. and M.V.; formal analyses: M.P. and P.T.
Corresponding authors
Correspondence to Mary K. Hayden or Julia A. Segre.
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Extended data figures and tables
Extended Data Fig. 1 Schematic of samples used for shotgun metagenomic sequencing of initial and longitudinal analyses.
(a) Each point represents a sample. Samples for each body site are shown as a function of subject. Abbreviations for body sites are defined as An Perianal; Fg fingertips/palm; Ic inguinal crease; N nares; and Tw Toe webs. Samples for select body sites included but not displayed are external auditory canal samples from subjects 23, 28, 35, 46, and 53; neck sample from subject 3; buccal/tongue samples from subjects 27 and 39; tracheostomy sample from subject 43; axilla sample from subject 23. (b) Longitunal sampling for a subset of subjects is plotted as a function of survey period (Survey 1, Survey 2 and Survey 3) and body site as defined in a.
Source Data
Extended Data Fig. 2 Distribution of gut species across body sites by oxygen tolerance.
We analyzed the distribution (y-axis) of the 48 most abundant species in peri-anal samples across various body sites (x-axis). Each point represents the square root abundance of one species in a sample. Each panel corresponds to a different oxygen tolerance category: aerobe, aerotolerant, anaerobe, or facultative anaerobe. When the boxplot appears only as a line, it indicates that the median abundance is approximately zero and overlaps with the interquartile range. If only the upper half of the boxplot is visible, it suggests the data are highly skewed toward the median, with the 75th percentile exceeding the median. Conversely, when the lower part of the boxplot is visible, it indicates that the 25th percentile is less than the median. Statistical significance was assessed using the Wilcoxon rank-sum test.
Source Data
Extended Data Fig. 3 Probability of recovering MAGs from pairs of species based on presence/absence matrix.
Yellow indicates species pairs that were found to co-occur less frequently than expected by chance (p < 0.05); blue indicates species pairs found to co-occur more frequently than expected by chance (p < 0.05); gray indicates species pairs for which a negative or positive association could not be determined. P. stuartii, P. mirabilis, and K. pneumoniae were detected together more frequently than expected by chance and tended to co-occur with gut commensals such as Bifidobacterium breve and Bacteroides fragilis. In contrast, S. pettenkoferi tended to co-occur with Staphylococcus and Corynebacterium species as well as C. auris.
Source Data
Extended Data Fig. 4 Aggregate skin colonization of residents with bacterial pathogens and persistent antibiotic resistance gene profiles.
(a) Presence of species (y-axis) for each resident (x-axis) on skin (inguinal crease, fingertips, toe webs, and axilla) and nares. Presence is defined in two ways. First, an asterisk indicates residents for whom MAGs which were at least 90% complete were recovered for each species, as defined by >90% checkM2 completeness and >90% aligned. Second, colors indicate residents for whom genomes were >50% (present, navy blue color) or <50% (absent, gray color) covered in at least one sample, based on read mapping. We use this second definition of presence since if a genome is at least 50% covered, but does not yield a MAG, there is a high likelihood that species is present. Subjects 7, 32, 39 and 43 are not shown, as no MAGs from skin sites other than peri-anal skin were recovered for these subjects. (b) Each panel represents a subject. Body sites are displayed on the y-axis and time point is displayed on the x-axis. Orange boxes are displayed where a sample was sequenced for that subject, site, and time point. Crosses are displayed in cases where bla-KPC was detected by SRST2. Persistent detection of bla-KPC is observed in subject 14, 23, 31, 53, and 54 with potential persistence observed in subjects 27 and 46. Persistence is defined as the detection of a gene at consecutive monthly surveys. Tw, toe webs; N, nares; Ic, inguinal crease; Fg, Fingertips/palm; An, peri-anus.
Source Data
Extended Data Fig. 5 Concordance between ANI, phylogenomics, and ST/inStrain for identifying K. pneumoniae strain sharing across subjects.
Plot illustrates the concordance between three methods (phylogeny, ANI, and ST/inStrain) in identifying strain sharing for K. pneumoniae sequence types across all subjects. Phylogeny identified ST147 K. pneumoniae amongst 16 subjects; ANI amongst an set of 12 subjects; and ST/inStrain amongst 10 subjects with complete overlap of methods for 7 subjects and partial overlap of methods for another 7 subjects. Phylogeny, ANI, and ST/inStrain all agreed for ST307 K. pneumoniae as present amongst 3 subjects.
Source Data
Extended Data Fig. 6 t-Stochastic Neighbor Embedding (t-SNE) clustering of pan-genome vs. core-genome distance.
Left Panel: ST131 E.coli gene presence/absence profiles indicate the presence of two clusters of ST131, consistent with the SNP analysis. Right Panel: ST147 K. pneumoniae gene presence/absence profiles do not split into multiple clusters.
Source Data
Extended Data Fig. 7 Pattern of MAG recovery and strain persistence or replacement over time within individuals and body sites.
Each panel illustrates the recovery of a MAG for a specific subject and body site (Fg: fingertips, Ic: inguinal crease, N: nares, Tw: toe webs). The x-axis represents the survey periods (1, 2, 3), and the y-axis shows the species for which MAGs were recovered. A circle or triangle indicates that a MAG was recovered for that species in that subject, body site, and time point. Additionally, triangles signify clonal colonization within a body site (<100 SNPs, as identified by inStrain). Strain persistence within a body site is indicated by triangles across time points, while strain replacement is reflected by a combination of circles and triangles within a single body site. Colors correspond to species as in Fig. 1.
Source Data
Extended Data Fig. 8 SNVs between samples of each species.
Histograms displaying the number of sample pairs (y-axis) that differ by the number of recombination-corrected SNVs (x-axis) for each species where sharing between multiple individuals was identified, as determined by Snippy, a read-based approach. The red line demarcates 30 SNVs.
Source Data
Extended Data Fig. 9 Regional spread, personalized diversification, and sharing of C. auris among roommates.
(a) Histograms of the tree distances separating all isolates collected from a single subject from each another. Frequencies of bins (y-axis) are plotted as a function of the tree distance (x-axis). If all isolates were identical the tree distance would be 0, while if all isolates were 100% distinct, the tree distance would be 1. (b) Violin plot of the number of SNVs separating same subject comparisons relative to different subject comparisons. The red dots highlight the within group means. (c) Each boxplot box demarcates the first and third quartiles of the hamming distance separating samples within each group, while the horizontal black lines within each box define the median distance. The black points within each boxplot represent the within group means. Two sets of roommates were surveilled. Room 1 included subjects 2, 4, 28, and 48. Room 2 included subjects 5, 14, 15, and 23.
Source Data
Extended Data Fig. 10 Geographically dispersed nursing homes experience strain sharing of pathogens.
(a) Rank abundance of target species as in Fig. 1 and M. slooffiae genomes detected in >1900 publicly available shotgun metagenomic samples. Each panel represents a different facility and body site (skin, stool). The relative abundance of target species is shown (y-axis) sorted from lowest to highest total abundance (x-axis). (b) Prevalence of each species within samples from each facility. Presence was determined using 50% breadth of genome coverage threshold. (c) Translated single copy marker gene tree for E. coli MAGs identified in all nursing homes, integrated with the publicly available reference genomes, which encompass sequence types ST131, ST73, ST95, and ST69, which are known to cause bloodstream or urinary tract infection. (d) ANI networks of genomes of labeled species from RI, CT, and MA facilities. Across all networks, each node represents a MAG. Lines connecting nodes are represented if pairwise ANI reaches or exceeds 99.95%.
Source Data
Supplementary information
Supplementary Information
This file contains Supplementary Figs. 1–8.
Reporting Summary
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Supplementary Tables
Supplementary Tables 1–14.
Source data
Source Data Figs. 1–4 and Source Data Extended Data Figs. 1–10.
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Proctor, D.M., Sansom, S.E., Deming, C. et al. Clonal Candida auris and ESKAPE pathogens on the skin of residents of nursing homes. Nature (2025). https://doi.org/10.1038/s41586-025-08608-9
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Received:17 August 2023
Accepted:07 January 2025
Published:26 February 2025
DOI:https://doi.org/10.1038/s41586-025-08608-9
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