Genomic Surveillance Reveals Global Spread of Macrolide-Resistant Bordetella pertussis Linked to Vaccine Changes

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Abstract

The resurgence of whooping cough in regions utilizing acellular pertussis vaccines underscopes emerging public health challenges. Here, we characterized 178 Bordetella pertussis isolates collected from patients across all age groups in Shanghai (2018-2024) to assess genomic evolution and antibiotic susceptibility. Macrolide resistance to erythromycin, azithromycin, clarithromycin and clindamycin escalated from ≤50% (pre-2020) to nearly 100% (post-2020), mechanistically linked to the 23S rRNA A2047G mutation. Genome-based analysis identified a genotype MT28- ptxP3 -MRBP rapidlly dominated post-2020, exhibiting significantly higher prevalence in adults versus than age groups. Phylogenetic analysis of 178 Shanghai and 1596 global genomes revealed two major lineages corresponding to ptxP1 and ptxP3 alleles. MT28- ptxP3 -MRBP cluster was identified in France, Japan and the United States in 2024, indicating potential cross-border dissemination. These findings advocate for intergrated surveillance spanning all ages and international borders to contain the global spread of macrolide-resistant Bordetella pertussis .

Highlights

  • After 2020, MT28- ptxP3 -MRBP lineage rapidly dominated, comprising 61.7% of isolates.

  • MT28- ptxP3 -MRBP exhibits a significant transmission advantage among older individuals.

  • The primary affected group shifted from ≤36 months (pre-2020) to 37 months–18 years (post-2020).

  • Macrolide resistance rose from ≤50% pre-2020 to nearly 100% post-2020, with all resistant isolates carrying the A2047G mutation.

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