Sputum DNA sequencing in cystic fibrosis: non-invasive access to the lung microbiome and to pathogen details

Background Cystic fibrosis (CF) is a life-threatening genetic disorder, characterized by chronic microbial lung infections due to abnormally viscous mucus secretions within airways. The clinical management of CF typically involves regular respiratory-tract cultures in order to identify pathogens and...

Full description

Saved in:
Bibliographic Details
Published in:Microbiome Vol. 5; no. 1; p. 20
Main Authors: Feigelman, Rounak, Kahlert, Christian R., Baty, Florent, Rassouli, Frank, Kleiner, Rebekka L., Kohler, Philipp, Brutsche, Martin H., von Mering, Christian
Format: Journal Article
Language:English
Published: London BioMed Central 10.02.2017
Springer Nature B.V
Subjects:
Bacteria - genetics
Bacteria - isolation & purification
Bacteria - pathogenicity
Bioinformatics
Biomedical and Life Sciences
Biomedicine
Cystic Fibrosis - microbiology
Drug Resistance, Bacterial - genetics
Genetic Variation
Genomic Islands
High-Throughput Nucleotide Sequencing
Humans
Lung - microbiology
Medical Microbiology
Metagenome
Metagenomics
Microbial Ecology
Microbial Genetics and Genomics
Microbiology
Microbiota - genetics
Multilocus Sequence Typing
Respiratory Tract Infections - microbiology
Sputum - microbiology
Virology
WGS metagenomic sequencing
Cystic fibrosis
Sputum
Lung metagenome
COPD
ISSN:2049-2618, 2049-2618
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Background Cystic fibrosis (CF) is a life-threatening genetic disorder, characterized by chronic microbial lung infections due to abnormally viscous mucus secretions within airways. The clinical management of CF typically involves regular respiratory-tract cultures in order to identify pathogens and to guide treatment. However, culture-based methods can miss atypical or slow-growing microbes. Furthermore, the isolated microbes are often not classified at the strain level due to limited taxonomic resolution. Results Here, we show that untargeted metagenomic sequencing of sputum DNA can provide valuable information beyond the possibilities of culture-based diagnosis. We sequenced the sputum of six CF patients and eleven control samples (including healthy subjects and chronic obstructive pulmonary disease patients) without prior depletion of human DNA or cell size selection, thus obtaining the most unbiased and comprehensive characterization of CF respiratory tract microbes to date. We present detailed descriptions of the CF and healthy lung microbiome, reconstruct near complete pathogen genomes, and confirm that the CF lungs consistently exhibit reduced microbial diversity. Crucially, the obtained genomic sequences enabled a detailed identification of the exact pathogen strain types, when analyzed in conjunction with existing multi-locus sequence typing databases. We also detected putative pathogenicity islands and indicators of antibiotic resistance, in good agreement with independent clinical tests. Conclusions Unbiased sputum metagenomics provides an in-depth profile of the lung pathogen microbiome, which is complementary to and more detailed than standard culture-based reporting. Furthermore, functional and taxonomic features of the dominant pathogens, including antibiotics resistances, can be deduced—supporting accurate and non-invasive clinical diagnosis.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 14
content type line 23
ISSN:2049-2618
2049-2618
DOI:10.1186/s40168-017-0234-1