The airway metagenome in Pseudomonas aeruginosa associated severe asthma

Introduction:Pseudomonas aeruginosa (PA) complicates chronic respiratory diseases including COPD and bronchiectasis, however, its role in severe asthma and on its associated airway microbiome lacks investigation. Methods: N=75 airway specimens from individuals with severe asthma (53 on GINA step 4 and 22 on GINA step 5 therapy) were prospectively obtained across two hospitals in Singapore and subjected to shotgun metagenomic sequencing to evaluate the airway microbiome and antimicrobial resistome in the setting of PA positivity (PA+). Results: 16% of individuals (N=12) demonstrated airway PA+. A higher proportion of PA+ patients were on GINA step 5 (32%; 7/22) as compared to step 4 therapy (9%; 5/53) (p=0.04). PA+ severe asthma exhibits a higher abundance of Achromobacter xyloxidans (AX) and Moraxella catarrhalis (MC) in the airway microbiome and, despite a lower overall microbial diversity, PA+ severe asthma demonstrates greater diversity in antimicrobial resistance (AMR) gene expression (p=0.02). This enhanced AMR gene diversity tightly correlates to the observation that PA, AX and MC were among the top microbial species harbouring the greatest number of AMR genes (i.e. 91, 70 and 35, respectively). Conclusion: Metagenomics reveals important characteristics of the airway microbiome and accompanying resistome in PA+ severe asthma. Future work should focus on the clinical implications of these findings. Funding: This research is supported by the Singapore Ministry of Health’s National Medical Research Council under its Clinician-Scientist Individual Research Grant (CS-IRG) (MOH-000141) (S. H.C) and Clinician Scientist Award (CSA) (MOH-000710) (S.H.C).