A global perspective on the genomics of Moraxella catarrhalis

<i>Moraxella catarrhalis</i> is an opportunistic pathogen of the human respiratory tract, primarily associated with otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults. Despite its clinical importance, the genomic diversity and functional specialization of <i>M. catarrhalis</i> remain insufficiently characterized. This study aimed to analyse the global genetic diversity of <i>M. catarrhalis</i> using whole-genome sequencing to identify phylogenetic lineages, antimicrobial resistance patterns and key virulence factors. Phylogenomic analysis of 345 publicly available genomes identified 3 phylogroups, of which 1 exhibited significant genomic divergence and was excluded from further analyses due to its potential classification as a separate species. The remaining two phylogroups corresponded to previously described seroresistant and serosensitive lineages. Phylogroup B exhibited a higher prevalence of antimicrobial resistance genes, particularly <i>bro-1</i> and <i>bro-2</i>, while phylogroup A exhibited unique metabolic adaptation, including genes encoding for the DppB-DppC-DppD dipeptide transport system. Both phylogroups shared crucial virulence factors, including UspA1 and UspA2, which facilitate adhesion and immune evasion. Potential therapeutic targets were identified, including PilQ, essential for type IV pilus biogenesis, and CopB, which plays a key role in iron acquisition and immune evasion. Overall, these findings highlight the significance of phylogenomics approaches in elucidating the genetic mechanisms underlying pathogenicity and resistance in <i>M. catarrhalis</i>, providing insights for future therapeutic and preventive strategies.