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Journal article

Resistome analyses of sputum from COPD and healthy subjects reveals bacterial load-related prevalence of target genes

Abstract:

Background:
Antibiotic resistance is a major global threat. We hypothesised that the chronic obstructive pulmonary disease (COPD) airway is a reservoir of antimicrobial resistance genes (ARGs) that associate with microbiome-specific COPD subgroups.


Objective:
To determine the resistance gene profiles in respiratory samples from COPD patients and healthy volunteers.


Methods:
Quantitative PCR targeting 279 specific ARGs was used to profile the resistomes in sputum from subjects with COPD at stable, exacerbation and recovery visits (n=55; COPD-BEAT study), healthy controls with (n=7) or without (n=22) exposure to antibiotics in the preceding 12 months (EXCEED study) and in bronchial brush samples from COPD (n=8) and healthy controls (n=7) (EvA study).


Results:
ARG mean (SEM) prevalence was greater in stable COPD samples (35.2 (1.6)) than in healthy controls (27.6 (1.7); p=0.004) and correlated with total bacterial abundance (r2=0.23; p<0.001). Prevalence of ARG positive signals in individuals was not related to COPD symptoms, lung function or their changes at exacerbation. In the COPD subgroups designated High γProteobacteria and High Firmicutes, ARG prevalence was not different at stable state but significantly declined from stable through exacerbation to recovery in the former (p=0.011) without changes in total bacterial abundance. The ARG patterns were similar in COPD versus health, COPD microbiome-subgroups and between sputum and bronchoscopic samples independent of antibiotic exposure in the last 12 months.


Conclusions:
ARGs are highly prevalent in sputum, broadly in proportion to bacterial abundance in both healthy and COPD subjects. Thus, COPD appears to be an ARG reservoir due to high levels of bacterial colonisation.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1136/thoraxjnl-2019-213485

Authors


More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Target Discovery Institute
Role:
Author
ORCID:
0000-0002-9993-2478


Publisher:
BMJ
Journal:
Thorax More from this journal
Volume:
75
Issue:
1
Publication date:
2019-11-07
Acceptance date:
2019-09-09
DOI:
EISSN:
1468-3296
ISSN:
0040-6376
Pmid:
31699806


Language:
English
Keywords:
Pubs id:
pubs:1071207
UUID:
uuid:478e2d90-7e80-4bb8-a1b3-e57cbdf7b925
Local pid:
pubs:1071207
Source identifiers:
1071207
Deposit date:
2019-12-09

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