Microbial virulence in bronchiectasis: Insights from the CAMEB 2 cohort

<bold>Rationale:</bold> Assessing bacterial virulence using next-generation sequencing (NGS) can provide insight into the functional role of microbiomes. <bold>Methods:</bold> Genus-specific bacterial reads from the Cohort of Asian and Matched European Bronchiectasis 2 (CAMEB 2) were extracted and mapped to virulence genes in the virulence factor database (VFDB). Virulence richness and profile (i.e. count and abundance of distinct virulence genes) were compared across regions (Singapore-Kuala Lumpur: SG-KL and Dundee-Milan: DD-MI) and disease severity (as BSI). <bold>Results:</bold> <italic>Pseudomonas</italic>, a key bronchiectasis pathogen (346 genes in CAMEB 2) demonstrates comparable virulence richness and profile across geographic regions and/or disease severity. <italic>Klebsiella</italic>, the second richest, harbours more virulence genes in the SG/KL cohort (112) versus DD/MI (54) with virulence richness correlating to bronchiectasis severity. <italic>Streptococcus</italic>, the most abundant bacterial genus, shows higher richness in DD/MI (61) versus SG/KL (26), however, mainly associates with moderate disease. Interestingly, an increased number of adherence genes serves as surrogate for an increased overall virulence. <bold>Conclusion:</bold> Variation in bacterial virulence is detectable by NGS across geographic regions and bronchiectasis severity offering an exploratory route to understanding functional aspects of microbiomes. <bold>Funding:</bold> This work is supported by the Singapore Ministry of Health’s National Medical Research Council under the Clinician-Scientist Individual Research Grant MOH-001356 (S.H.C) and a Clinician-Scientist Award MOH-000710 (S.H.C) and the Singapore Ministry of Education under its AcRF Tier 1 Grant (RT1/22) (S.H.C).