BacCapSeq: a Platform for Diagnosis and Characterization of Bacterial Infections

ABSTRACT We report a platform that increases the sensitivity of high-throughput sequencing for detection and characterization of bacteria, virulence determinants, and antimicrobial resistance (AMR) genes. The system uses a probe set comprised of 4.2 million oligonucleotides based on the Pathosystems...

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Autores principales:	Orchid M. Allicock, Cheng Guo, Anne-Catrin Uhlemann, Susan Whittier, Lokendra V. Chauhan, Joel Garcia, Adam Price, Stephen S. Morse, Nischay Mishra, Thomas Briese, W. Ian Lipkin
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	antibiotic resistance bacterial identification diagnostics sequencing Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/46f99f6bb6794d3191a38b4ff5ddaf58
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spelling	oai:doaj.org-article:46f99f6bb6794d3191a38b4ff5ddaf582021-11-15T15:58:20ZBacCapSeq: a Platform for Diagnosis and Characterization of Bacterial Infections10.1128/mBio.02007-182150-7511https://doaj.org/article/46f99f6bb6794d3191a38b4ff5ddaf582018-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02007-18https://doaj.org/toc/2150-7511ABSTRACT We report a platform that increases the sensitivity of high-throughput sequencing for detection and characterization of bacteria, virulence determinants, and antimicrobial resistance (AMR) genes. The system uses a probe set comprised of 4.2 million oligonucleotides based on the Pathosystems Resource Integration Center (PATRIC) database, the Comprehensive Antibiotic Resistance Database (CARD), and the Virulence Factor Database (VFDB), representing 307 bacterial species that include all known human-pathogenic species, known antimicrobial resistance genes, and known virulence factors, respectively. The use of bacterial capture sequencing (BacCapSeq) resulted in an up to 1,000-fold increase in bacterial reads from blood samples and lowered the limit of detection by 1 to 2 orders of magnitude compared to conventional unbiased high-throughput sequencing, down to a level comparable to that of agent-specific real-time PCR with as few as 5 million total reads generated per sample. It detected not only the presence of AMR genes but also biomarkers for AMR that included both constitutive and differentially expressed transcripts. IMPORTANCE BacCapSeq is a method for differential diagnosis of bacterial infections and defining antimicrobial sensitivity profiles that has the potential to reduce morbidity and mortality, health care costs, and the inappropriate use of antibiotics that contributes to the development of antimicrobial resistance.Orchid M. AllicockCheng GuoAnne-Catrin UhlemannSusan WhittierLokendra V. ChauhanJoel GarciaAdam PriceStephen S. MorseNischay MishraThomas BrieseW. Ian LipkinAmerican Society for Microbiologyarticleantibiotic resistancebacterial identificationdiagnosticssequencingMicrobiologyQR1-502ENmBio, Vol 9, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	antibiotic resistance bacterial identification diagnostics sequencing Microbiology QR1-502
spellingShingle	antibiotic resistance bacterial identification diagnostics sequencing Microbiology QR1-502 Orchid M. Allicock Cheng Guo Anne-Catrin Uhlemann Susan Whittier Lokendra V. Chauhan Joel Garcia Adam Price Stephen S. Morse Nischay Mishra Thomas Briese W. Ian Lipkin BacCapSeq: a Platform for Diagnosis and Characterization of Bacterial Infections
description	ABSTRACT We report a platform that increases the sensitivity of high-throughput sequencing for detection and characterization of bacteria, virulence determinants, and antimicrobial resistance (AMR) genes. The system uses a probe set comprised of 4.2 million oligonucleotides based on the Pathosystems Resource Integration Center (PATRIC) database, the Comprehensive Antibiotic Resistance Database (CARD), and the Virulence Factor Database (VFDB), representing 307 bacterial species that include all known human-pathogenic species, known antimicrobial resistance genes, and known virulence factors, respectively. The use of bacterial capture sequencing (BacCapSeq) resulted in an up to 1,000-fold increase in bacterial reads from blood samples and lowered the limit of detection by 1 to 2 orders of magnitude compared to conventional unbiased high-throughput sequencing, down to a level comparable to that of agent-specific real-time PCR with as few as 5 million total reads generated per sample. It detected not only the presence of AMR genes but also biomarkers for AMR that included both constitutive and differentially expressed transcripts. IMPORTANCE BacCapSeq is a method for differential diagnosis of bacterial infections and defining antimicrobial sensitivity profiles that has the potential to reduce morbidity and mortality, health care costs, and the inappropriate use of antibiotics that contributes to the development of antimicrobial resistance.
format	article
author	Orchid M. Allicock Cheng Guo Anne-Catrin Uhlemann Susan Whittier Lokendra V. Chauhan Joel Garcia Adam Price Stephen S. Morse Nischay Mishra Thomas Briese W. Ian Lipkin
author_facet	Orchid M. Allicock Cheng Guo Anne-Catrin Uhlemann Susan Whittier Lokendra V. Chauhan Joel Garcia Adam Price Stephen S. Morse Nischay Mishra Thomas Briese W. Ian Lipkin
author_sort	Orchid M. Allicock
title	BacCapSeq: a Platform for Diagnosis and Characterization of Bacterial Infections
title_short	BacCapSeq: a Platform for Diagnosis and Characterization of Bacterial Infections
title_full	BacCapSeq: a Platform for Diagnosis and Characterization of Bacterial Infections
title_fullStr	BacCapSeq: a Platform for Diagnosis and Characterization of Bacterial Infections
title_full_unstemmed	BacCapSeq: a Platform for Diagnosis and Characterization of Bacterial Infections
title_sort	baccapseq: a platform for diagnosis and characterization of bacterial infections
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/46f99f6bb6794d3191a38b4ff5ddaf58
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BacCapSeq: a Platform for Diagnosis and Characterization of Bacterial Infections

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