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Co-occurrence analysis relates a macrolide resistome to the pulmonary microbiome in chronic respiratory disease

Jayanth Kumar Narayana, Micheál Mac Aogáin, Kenny Lau Jia Xu, Zhao Cai, Rikky Purbojati, Daniela Drautz-Moses, Nicolas Gaultier, Tavleen Jaggi, Pei Yee Tiew, Thun How Ong, Mariko Siyue Koh, Albert Yick Hou Lim, John Arputhan Abisheganaden, Krasimira Tsaneva-Atanasova, Stephan Schuster, Sanjay Haresh Chotirmall
European Respiratory Journal 2020 56: 4934; DOI: 10.1183/13993003.congress-2020.4934
Jayanth Kumar Narayana
1Lee Kong Chian School of Medicine, NTU, Singapore, Singapore
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  • For correspondence: jayanthk001@e.ntu.edu.sg
Micheál Mac Aogáin
1Lee Kong Chian School of Medicine, NTU, Singapore, Singapore
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Kenny Lau Jia Xu
2Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore
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Zhao Cai
2Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore
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Rikky Purbojati
2Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore
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Daniela Drautz-Moses
2Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore
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Nicolas Gaultier
2Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore
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Tavleen Jaggi
1Lee Kong Chian School of Medicine, NTU, Singapore, Singapore
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Pei Yee Tiew
1Lee Kong Chian School of Medicine, NTU, Singapore, Singapore
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Thun How Ong
3Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore
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Mariko Siyue Koh
3Department of Respiratory and Critical Care Medicine, Singapore General Hospital, Singapore, Singapore
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Albert Yick Hou Lim
4Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore, Singapore
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John Arputhan Abisheganaden
4Department of Respiratory and Critical Care Medicine, Tan Tock Seng Hospital, Singapore, Singapore
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Krasimira Tsaneva-Atanasova
5Department of Mathematics, College of Engineering, Mathematics and Physical Sciences, University of Exeter, Exeter, United Kingdom
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Stephan Schuster
2Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore, Singapore
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Sanjay Haresh Chotirmall
1Lee Kong Chian School of Medicine, NTU, Singapore, Singapore
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Abstract

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).

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Footnotes

Cite 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).

  • Copyright ©the authors 2020
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Co-occurrence analysis relates a macrolide resistome to the pulmonary microbiome in chronic respiratory disease
Jayanth Kumar Narayana, Micheál Mac Aogáin, Kenny Lau Jia Xu, Zhao Cai, Rikky Purbojati, Daniela Drautz-Moses, Nicolas Gaultier, Tavleen Jaggi, Pei Yee Tiew, Thun How Ong, Mariko Siyue Koh, Albert Yick Hou Lim, John Arputhan Abisheganaden, Krasimira Tsaneva-Atanasova, Stephan Schuster, Sanjay Haresh Chotirmall
European Respiratory Journal Sep 2020, 56 (suppl 64) 4934; DOI: 10.1183/13993003.congress-2020.4934

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Co-occurrence analysis relates a macrolide resistome to the pulmonary microbiome in chronic respiratory disease
Jayanth Kumar Narayana, Micheál Mac Aogáin, Kenny Lau Jia Xu, Zhao Cai, Rikky Purbojati, Daniela Drautz-Moses, Nicolas Gaultier, Tavleen Jaggi, Pei Yee Tiew, Thun How Ong, Mariko Siyue Koh, Albert Yick Hou Lim, John Arputhan Abisheganaden, Krasimira Tsaneva-Atanasova, Stephan Schuster, Sanjay Haresh Chotirmall
European Respiratory Journal Sep 2020, 56 (suppl 64) 4934; DOI: 10.1183/13993003.congress-2020.4934
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