Genomic epidemiology of erythromycin-resistant <i>Bordetella pertussis</i> in China

Macrolides such as erythromycin are the empirical treatment of <i>Bordetella pertussis</i> infections. China has experienced an increase in erythromycin-resistant <i>B. pertussis</i> isolates since they were first reported in 2013. Here, we undertook a genomic study on Chinese <i>B. pertussis</i> isolates from 2012 to 2015 to elucidate the origins and phylogenetic relationships of erythromycin-resistant <i>B. pertussis</i> isolates in China. A total of 167 Chinese <i>B. pertussis</i> isolates were used for antibiotic sensitivity testing and multiple locus variable-number tandem repeat (VNTR) analysis (MLVA). All except four isolates were erythromycin-resistant and of the four erythromycin-sensitive isolates, three were <i>non-ptxP1</i>. MLVA types (MT), MT55, MT104 and MT195 were the predominant types. Fifty of those isolates were used for whole genome sequencing and phylogenetic analysis. Genome sequencing and phylogenetic analysis revealed three independent erythromycin-resistant lineages and all resistant isolates carried a mutation in the 23S rRNA gene. A novel <i>fhaB3</i> allele was found uniquely in Chinese <i>ptxP1</i> isolates and these Chinese <i>ptxP1-ptxA1-fhaB3</i> had a 5-fold higher mutation rate than the global <i>ptxP1-ptxA1 B. pertussis</i> population. Our results suggest that the evolution of Chinese <i>B. pertussis</i> is likely to be driven by selection pressure from both vaccination and antibiotics. The emergence of the new non-vaccine <i>fhaB3</i> allele in Chinese <i>B. pertussis</i> population may be a result of selection from vaccination, whereas the expansion of <i>ptxP1-fhaB3</i> lineages was most likely to be the result of selection pressure from antibiotics. Further monitoring of <i>B. pertussis</i> in China is required to better understand the evolution of the pathogen.