Genomic attributes of airway commensal bacteria and mucosa.

Orla O'Carroll, Sofia K Forslund, Nitin Kumar, Leah Cuthbertson, Jonathan S Ish-Horowicz, Claire N McBrien, Colin Churchward, Jeremy C Parker, Keir E Lewis, Kian Fan Chung, Joy Creaser-Thomas, Mark Andrews, Robin Ghosal, Stefan Piatek, Saffron A G Willis-Owen, Elena M Turek, A William Musk, Sarah Filippi, Miriam F Moffatt, Julian M Hopkin, William O C Cookson, Michael J Cox, Aisling McGowan, Conor Burke, Trevor D Lawley, Alan James, John Faul, Till Birkner, Michael Hunter, Jennie Hui, Sarah Dwyer, Michael T Olanipekun, Gwyneth A Davies, Marc-Emmanuel Dumas, Ulrike Löber, Theda U P Bartolomaeus

Journal: Communications biology 2024;7(1):171

PMID: 38347162

Abstract

Microbial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals. Clinically relevant genes encode antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. Using whole-genome content we identify dysbiotic features that may influence asthma and chronic obstructive pulmonary disease. We match isolate gene content to transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways to sustain host interactions with microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosa in lung diseases of global significance.

© 2024. The Author(s).

Address: National Heart and Lung Institute, Imperial College London, London, UK.; Max Delbrück Center for Molecular Medicine (MDC), 13125, Berlin, Germany.; Experimental and Clinical Research Center, A Cooperation of Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Lindenberger Weg 80, 13125, Berlin, Germany.; DZHK (German Centre for Cardiovascular Research), Partner Site, 10785, Berlin, Germany.; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany.; National Heart and Lung Institute, Imperial College London, London, UK.; Department of Mathematics, Imperial College London, London, UK.; Department of Respiratory Medicine, Connolly Hospital, Dublin, Ireland.; Population Data Science and Health Data Research UK BREATHE Hub, Swansea University Medical School, Swansea University, Swansea, UK.; College of Medicine, Institute of Life Science, Swansea University, Swansea, UK.; College of Medicine, Institute of Life Science, Swansea University, Swansea, UK.; Respiratory Medicine, Hywel Dda University Health Board, Llanelli, UK.; College of Medicine, Institute of Life Science, Swansea University, Swansea, UK.; Respiratory Medicine, Hywel Dda University Health Board, Llanelli, UK.; Max Delbrück Center for Molecular Medicine (MDC), 13125, Berlin, Germany.; Experimental and Clinical Research Center, A Cooperation of Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Lindenberger Weg 80, 13125, Berlin, Germany.; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany.; Host-Microbiota Interactions Laboratory, Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, UK.; School of Population and Global Health, The University of Western Australia, Perth, WA, Australia.; Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Perth, WA, Australia.; Department of Respiratory Medicine Sir Charles Gairdner Hospital, Perth, WA, Australia.; School of Population and Global Health, The University of Western Australia, Perth, WA, Australia.; Busselton Population Medical Research Institute, Sir Charles Gairdner Hospital, Perth, WA, Australia.; School of Population and Global Health, The University of Western Australia, Perth, WA, Australia.; Department of Respiratory Medicine Sir Charles Gairdner Hospital, Perth, WA, Australia.; Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Perth, WA, Australia.; National Heart and Lung Institute, Imperial College London, London, UK.; Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.; U1283 INSERM / UMR8199 CNRS, Institut Pasteur de Lille, Lille University Hospital, European Genomic Institute for Diabetes, University of Lille, Lille, France.; McGill Genome Centre, McGill University, Montréal, QC, Canada.; Department of Mathematics, Imperial College London, London, UK.; University of Birmingham College of Medical and Dental Sciences, 150183, Institute of Microbiology and Infection, Birmingham, UK.; Max Delbrück Center for Molecular Medicine (MDC), 13125, Berlin, Germany. [email protected].; Experimental and Clinical Research Center, A Cooperation of Charité-Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine, Lindenberger Weg 80, 13125, Berlin, Germany. [email protected].; DZHK (German Centre for Cardiovascular Research), Partner Site, 10785, Berlin, Germany. [email protected].; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117, Berlin, Germany. [email protected].; Structural and Computational Biology Unit, European Molecular Biology Laboratory, Structural and Computational Biology Unit, 69117, Heidelberg, Germany. [email protected].; National Heart and Lung Institute, Imperial College London, London, UK. [email protected].; National Heart and Lung Institute, Imperial College London, London, UK. [email protected].
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