A global perspective on the genomics of Moraxella catarrhalis

Abstract

2.Moraxella catarrhalis is an opportunistic pathogen of the human respiratory tract, primarily associated with otitis media in children and exacerbations of chronic obstructive pulmonary disease (COPD) in adults. Despite its clinical importance, the genomic diversity and functional specialization of M. catarrhalis remain insufficiently characterized. This study aimed to analyze the global genetic diversity of M. catarrhalis using whole-genome sequencing to identify phylogenetic lineages, antimicrobial resistance patterns, and key virulence factors. Phylogenomic analysis of 345 publicly available genomes identified three phylogroups, of which one 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 bro-1 and bro-2, 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 to elucidate the genetic mechanisms underlying pathogenicity and resistance in M. catarrhalis, providing insights for future therapeutic and preventive strategies. 3. Impact statementThis study presents a comprehensive phylogenomic analysis of M. catarrhalis, expanding current knowledge of its genetic diversity, antimicrobial resistance, and virulence factors. By analyzing 345 global genomes, we identified three distinct phylogroups, one of which shows substantial genomic divergence, suggesting it may represent a novel species within the Moraxella genus. Our findings confirm the existence of seroresistant and serosensitive lineages, providing new insights into their metabolic adaptations and differential antibiotic resistance profiles. Notably, phylogroup B harbors a higher prevalence of {beta}-lactam resistance genes, while phylogroup A exhibits unique peptide transport systems. This work strengthens the evidence that phylogenomic approaches are essential to understand the evolutionary dynamics and pathogenic potential of M. catarrhalis. The identification of conserved virulence factors and potential therapeutic targets, such as PilQ and CopB, underscores the relevance of this pathogen in respiratory infections and the need for targeted interventions. Our results not only clarify the population structure of M. catarrhalis but also provide a valuable genomic framework for future studies on antimicrobial resistance and vaccine development, with broad utility for microbiologists, clinicians, and public health researchers. 4. Data summaryThe authors confirm all supporting data, code, and protocols have been provided within the article or through supplementary data files.