Genomic epidemiology and the evolution of erm(B)-mediated macrolide resistance in Campylobacter

<i>Campylobacter</i> is a major foodborne bacterial pathogen that has become increasingly resistant to clinically important antimicrobials. Of particular concern is the emergence of <i>erm</i>(B)-mediated macrolide resistance, which has been increasingly documented across <i>Campylobacter</i> isolates from diverse ecological reservoirs. In this study, we investigated the genomic characteristics and epidemiology of <i>erm</i>(B)-carrying clinical <i>Campylobacter</i> isolates from Shanghai, alongside a globally representative dataset of all publicly available strains. Among clinical isolates obtained from a diarrhoeal outpatient surveillance programme between 2020 and 2023 in Shanghai, China, 16% (80/500) were erythromycin-resistant, with 23.8% (19/80) testing positive for <i>erm</i>(B). The genomes of these isolates were sequenced to identify <i>erm</i>(B) gene alleles. Phylogenetic analyses, pairwise comparisons of core and accessory genomes and examination of shared alleles revealed horizontal gene transfer as the predominant mechanism driving the transmission of <i>erm</i>(B) between isolates from various sources. Poultry was identified as a key reservoir for human infections caused by <i>erm</i>(B)-positive <i>Campylobacter</i> isolates. Comparative pangenome analyses of <i>erm</i>(B)-positive and negative isolates identified multiple accessory elements associated with <i>erm</i>(B) acquisition, among which the IS607 family transposon-associated <i>tnpB</i> gene exhibited sequence and structural homology to functional progenitors of CRISPR-Cas nucleases. These findings expand our understanding of the epidemiology of <i>erm</i>(B)-mediated macrolide resistance in <i>Campylobacter</i> and underscore the urgent need for enhanced antimicrobial stewardship in poultry production and targeted surveillance programmes to curb the spread of resistance.