Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing

ABSTRACT Culture-independent methods that target genome fragments have shown promise in identifying certain pathogens, but the holy grail of comprehensive pathogen genome detection from microbiologically complex samples for subsequent forensic analyses remains a challenge. In the context of an inves...

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Autores principales:	Andre Mu, Jason C. Kwong, Nicole S. Isles, Anders Gonçalves da Silva, Mark B. Schultz, Susan A. Ballard, Courtney R. Lane, Glen P. Carter, Deborah A. Williamson, Torsten Seemann, Timothy P. Stinear, Benjamin P. Howden
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Klebsiella pneumoniae antimicrobial resistance metagenomics microbiome vancomycin-resistant enterococci Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a6c119ab5c64457cb79b1f1afda92ce6
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spelling	oai:doaj.org-article:a6c119ab5c64457cb79b1f1afda92ce62021-11-15T15:22:05ZReconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing10.1128/mSphere.00529-182379-5042https://doaj.org/article/a6c119ab5c64457cb79b1f1afda92ce62019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00529-18https://doaj.org/toc/2379-5042ABSTRACT Culture-independent methods that target genome fragments have shown promise in identifying certain pathogens, but the holy grail of comprehensive pathogen genome detection from microbiologically complex samples for subsequent forensic analyses remains a challenge. In the context of an investigation of a nosocomial outbreak, we used shotgun metagenomic sequencing of a human fecal sample and a neural network algorithm based on tetranucleotide frequency profiling to reconstruct microbial genomes and tested the same approach using rectal swabs from a second patient. The approach rapidly and readily detected the genome of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in the patient fecal specimen and in the rectal swab sample, achieving a level of strain resolution that was sufficient for confident transmission inference during a highly clonal outbreak. The analysis also detected previously unrecognized colonization of the patient by vancomycin-resistant Enterococcus faecium, another multidrug-resistant bacterium. IMPORTANCE The study results reported here perfectly demonstrate the power and promise of clinical metagenomics to recover genome sequences of important drug-resistant bacteria and to rapidly provide rich data that inform outbreak investigations and treatment decisions, independently of the need to culture the organisms.Andre MuJason C. KwongNicole S. IslesAnders Gonçalves da SilvaMark B. SchultzSusan A. BallardCourtney R. LaneGlen P. CarterDeborah A. WilliamsonTorsten SeemannTimothy P. StinearBenjamin P. HowdenAmerican Society for MicrobiologyarticleKlebsiella pneumoniaeantimicrobial resistancemetagenomicsmicrobiomevancomycin-resistant enterococciMicrobiologyQR1-502ENmSphere, Vol 4, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Klebsiella pneumoniae antimicrobial resistance metagenomics microbiome vancomycin-resistant enterococci Microbiology QR1-502
spellingShingle	Klebsiella pneumoniae antimicrobial resistance metagenomics microbiome vancomycin-resistant enterococci Microbiology QR1-502 Andre Mu Jason C. Kwong Nicole S. Isles Anders Gonçalves da Silva Mark B. Schultz Susan A. Ballard Courtney R. Lane Glen P. Carter Deborah A. Williamson Torsten Seemann Timothy P. Stinear Benjamin P. Howden Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing
description	ABSTRACT Culture-independent methods that target genome fragments have shown promise in identifying certain pathogens, but the holy grail of comprehensive pathogen genome detection from microbiologically complex samples for subsequent forensic analyses remains a challenge. In the context of an investigation of a nosocomial outbreak, we used shotgun metagenomic sequencing of a human fecal sample and a neural network algorithm based on tetranucleotide frequency profiling to reconstruct microbial genomes and tested the same approach using rectal swabs from a second patient. The approach rapidly and readily detected the genome of Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in the patient fecal specimen and in the rectal swab sample, achieving a level of strain resolution that was sufficient for confident transmission inference during a highly clonal outbreak. The analysis also detected previously unrecognized colonization of the patient by vancomycin-resistant Enterococcus faecium, another multidrug-resistant bacterium. IMPORTANCE The study results reported here perfectly demonstrate the power and promise of clinical metagenomics to recover genome sequences of important drug-resistant bacteria and to rapidly provide rich data that inform outbreak investigations and treatment decisions, independently of the need to culture the organisms.
format	article
author	Andre Mu Jason C. Kwong Nicole S. Isles Anders Gonçalves da Silva Mark B. Schultz Susan A. Ballard Courtney R. Lane Glen P. Carter Deborah A. Williamson Torsten Seemann Timothy P. Stinear Benjamin P. Howden
author_facet	Andre Mu Jason C. Kwong Nicole S. Isles Anders Gonçalves da Silva Mark B. Schultz Susan A. Ballard Courtney R. Lane Glen P. Carter Deborah A. Williamson Torsten Seemann Timothy P. Stinear Benjamin P. Howden
author_sort	Andre Mu
title	Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing
title_short	Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing
title_full	Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing
title_fullStr	Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing
title_full_unstemmed	Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing
title_sort	reconstruction of the genomes of drug-resistant pathogens for outbreak investigation through metagenomic sequencing
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/a6c119ab5c64457cb79b1f1afda92ce6
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Reconstruction of the Genomes of Drug-Resistant Pathogens for Outbreak Investigation through Metagenomic Sequencing

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