Genomic attributes of airway commensal bacteria and mucosa

Author:

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

Abstract

AbstractMicrobial 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.

Funder

Wellcome Trust

Office of Science, Government of Western Australia

Publisher

Springer Science and Business Media LLC

Reference102 articles.

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