Genomic epidemiology of erythromycin-resistant Bordetella pertussis in China

Abstract

Macrolides such as erythromycin are the empirical treatment of Bordetella pertussis infections. China has experienced an increase in erythromycin-resistant B. pertussis isolates since they were first reported in 2013. Here, we undertook a genomic study on Chinese B. pertussis isolates from 2012 to 2015 to elucidate the origins and phylogenetic relationships of erythromycin-resistant B. pertussis isolates in China. A total of 167 Chinese B. pertussis 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 non-ptxP1 . 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 fhaB3 allele was found uniquely in Chinese ptxP1 isolates and these Chinese ptxP1-ptxA1-fhaB3 had a 5-fold higher mutation rate than the global ptxP1-ptxA1 B. pertussis population. Our results suggest that the evolution of Chinese B. pertussis is likely to be driven by selection pressure from both vaccination and antibiotics. The emergence of the new non-vaccine fhaB3 allele in Chinese B. pertussis population may be a result of selection from vaccination, whereas the expansion of ptxP1-fhaB3 lineages was most likely to be the result of selection pressure from antibiotics. Further monitoring of B. pertussis in China is required to better understand the evolution of the pathogen.

The global prevalence ptxP3 lineage of Bordetella pertussis was rare in young Children with the Co-purified aPV vaccination: a 5 years retrospective study

“…Besides the A2047G mutation in 23S rRNA occurred in ptxP1-ER B. pertussis strains, a novel fhaB C5330T was also founded in all these strains. This fhaB3 lineage has been proved to be prevalence among China via expansions most likely due to antibiotic pressure [3]. This study also illustrated that the ptxP1/fhaB3-ER strains might be adapted to the copurified aPV.…”

“…Furthermore, we found that all the ptxP1-ER strains originated from a fhaB3 lineage, which seems to be selected from the wPV or antibiotic pressure [3]. Interestingly, although the ER/ptxP1 strains expanded all over the countries of China, the proportions of ptxP3 strains varied from less than 10% to about 50% in different areas of China, especially occurred much higher in developed areas [4,5].…”

Macrolide-Resistant Bordetella pertussis, Vietnam, 2016−2017

“…In Vietnam, the B. pertussis population comprises 2 major strains, MT27 and MT104 (Appendix Figure 2). The MT27 strain is common in industrialized countries but not in China (8,9). In contrast, the MT104 strain is not common in industrialized countries but frequent in China.…”

“…Genotyping assays revealed that MRBP strains in Vietnam were closely related to an MRBP strain identified in China. The major MLVA types reported recently in China are MT55, MT104, and MT195 (8,9). These types are closely related; they have only 1 difference at 1 VNTR locus.…”

“…A clinical strain of MT104-MRBP was first identified in 2012 in Shannxi, China. Subsequently, this clinical strain of MT104-MRBP was found throughout the country (9).…”