RT Journal Article SR Electronic T1 Co-occurrence analysis relates a macrolide resistome to the pulmonary microbiome in chronic respiratory disease JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 4934 DO 10.1183/13993003.congress-2020.4934 VO 56 IS suppl 64 A1 Jayanth Kumar Narayana A1 Micheál Mac Aogáin A1 Kenny Lau Jia Xu A1 Zhao Cai A1 Rikky Purbojati A1 Daniela Drautz-Moses A1 Nicolas Gaultier A1 Tavleen Jaggi A1 Pei Yee Tiew A1 Thun How Ong A1 Mariko Siyue Koh A1 Albert Yick Hou Lim A1 John Arputhan Abisheganaden A1 Krasimira Tsaneva-Atanasova A1 Stephan Schuster A1 Sanjay Haresh Chotirmall YR 2020 UL http://erj.ersjournals.com/content/56/suppl_64/4934.abstract AB Background: Macrolide antibiotics are increasingly used in frequent exacerbators with chronic respiratory disease (CRD) however the role of the airway resistome and its relationship to the host microbiome remains unknown.Methods: We derived airway microbiomes and corresponding resistomes using deep sequencing metagenomic approaches from airway specimens of individuals with and without CRD (severe asthma, COPD and bronchiectasis) (n=85). Gene-Microbe association networks were built using compositionality corrected general boosted linear models to determine possible microbial sources of the airway resistome.Results: Antibiotic resistance profiles exhibit variability across healthy and diseased states with greatest resistance observed in COPD and bronchiectasis. A ‘core’ airway resistome dominated by macrolide resistance but with high prevalence of β-lactam, fluoroquinolone and tetracycline resistance genes exists, and, is independent of disease status or prior antibiotic exposure. Dysbiosis of the respiratory microbiome is evident across CRDs and gene-microbe association networks of the ‘core’ resistome revealed Streptococcus and Actinomyces as potential microbial reservoirs of macrolide resistance including the ermX, ermF and msrD genes.Conclusion: Functional metagenomics of the airway reveals a core macrolide resistome harboured by the host microbiome with clinical implications for macrolide use across CRD.Funding: Singapore Ministry of Health’s National Medical Research Council under its Transition Award (NMRC/TA/0048/2016) (S.H.C); Clinician-Scientist Individual Research Grant (MOH-000141) (S.H.C) and the NTU Integrated Medical, Biological and Environmental Life Sciences (NIMBELS) [NIM/03/2018] (S.H.C).FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 4934.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).