Genomic differences among NTHi isolates from bronchiectasis, CAP, and COPD
Nontypeable Haemophilus influenzae (NTHi) is a major respiratory pathogen. We performed whole-genome sequencing and comparative genomic analysis of 3 NTHi isolates from bronchiectasis (n=1), community-acquired pneumonia (CAP; n=1), and chronic obstructive pulmonary disease (COPD; n=1). Three isolates were newly sequenced using Oxford Nanopore–Illumina hybrid assembly.Analyses included pan-genome, MLST, core genome SNP, accessory genome discriminant analysis, and pan-GWAS. MLST/core genome analysis showed high diversity without disease-specific clustering. Accessory genome analyses revealed differences by clinical source, with discriminant analysis partially separating bronchiectasis isolates. Pan-GWAS identified disease-associated accessory genes, with functional annotation linking bronchiectasis-associated genes to genome plasticity and COPD-associated genes to metabolism/nutrient uptake. Clinical heterogeneity in NTHi is associated with accessory genome variation, suggesting its role in adaptation to distinct respiratory environments.