Genomic insights into Bordetella pertussis evolution and macrolide resistance in Yiwu, China.

Pertussis, caused by Bordetella pertussis, remains a significant public health concern despite widespread vaccination. Recent increases in macrolide-resistant strains present additional challenges for treatment and control. Yiwu, China-a highly mobile and international city-offers a unique setting to study the genomic evolution and antimicrobial resistance of B. pertussis. In this study, 63 clinical isolates from Yiwu underwent whole-genome sequencing. Over 90% of isolates showed high resistance to macrolides. Genome sizes ranged from 3.53 to 4.15 Mb, with high GC content (67.69-67.80%) and variable repeat rates. Phylogenetic analysis, incorporating 14 international strains, revealed two distinct clades and lineage-specific variations in key vaccine antigen genes, indicating multiple origins and localized evolution. A comparative analysis between resistant and sensitive isolates identified an A2037G substitution in the 23S rRNA gene strongly associated with macrolide resistance. Additionally, 69 highly divergent genes related to transcriptional regulation, recombination, and membrane function were detected. Notably, two outer membrane efflux protein genes, opmD and oprM, showed nonsynonymous mutations potentially linked to resistance enhancement. The presence of genomic islands, prophages, and antigenic gene variation further underscores the dynamic evolution of B. pertussis in the region. This study highlights the urgent need for alternative therapies and improved vaccines, while also demonstrating the value of continued genomic surveillance. Insights into resistance-associated genes offer new targets for functional studies and may guide future strategies in pertussis control.