A Cross-Sectional Study Revealing the Emergence of Erythromycin-Resistant Bordetella pertussis Carrying ptxP3 Alleles in China

Xiaoying Wu; Qianqian Du; Dongfang Li; Lin Yuan; Qinghong Meng; Zhou Fu; Hongmei Xu; Kaihu Yao; Ruiqiu Zhao

doi:10.3389/fmicb.2022.901617

A Cross-Sectional Study Revealing the Emergence of Erythromycin-Resistant Bordetella pertussis Carrying ptxP3 Alleles in China

Front Microbiol. 2022 Jul 18:13:901617. doi: 10.3389/fmicb.2022.901617. eCollection 2022.

Authors

Xiaoying Wu¹, Qianqian Du², Dongfang Li³, Lin Yuan², Qinghong Meng², Zhou Fu⁴, Hongmei Xu¹, Kaihu Yao², Ruiqiu Zhao¹

Affiliations

¹ Department of Infectious Diseases, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Infection and Immunity, Chongqing, China.
² Beijing Key Laboratory of Pediatric Respiratory Infection Diseases, MOE Key Laboratory of Major Diseases in Children, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
³ BGI Pathogenesis Pharmaceutical Technology, BGI-Shenzhen, Shenzhen, China.
⁴ Department of Respiratory Diseases, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China.

Abstract

Background: Previous limited studies have identified that Bordetella pertussis (B. pertussis) isolates circulating in China possess distinct molecular features and high rates of erythromycin-resistance (ER). Their evolution and potential impact on the prevention and control of global pertussis are worthy of attention.

Methods: The present cross-sectional study involved 311 non-duplicate and unrelated B. pertussis strains isolated from Chinese children from 2017 to 2019. Their antimicrobial susceptibilities were assessed using both E-test strips and Kirby-Bauer (KB) disk diffusion methods. Seven virulence-related genes (ptxA, ptxC, ptxP, prn, fim2, fim3, and tcfA2) and the A2047G mutation in the 23S rRNA gene were detected by PCR. Based on the susceptibilities and genotypes, 50 isolates were selected for multi-locus variable-number tandem-repeat analysis (MLVA) typing and whole-genome sequencing.

Results: A total of 311 B. pertussis strains were isolated from children with a median age of 4 months (interquartile range: 2-9 months). Strains carrying the ptxP1 allele were more frequent (84.9%, 264/311), were always ER (except for one strain), and were mainly related to ptxA1/ptxC1/prn1 alleles (99.6%, 263/264). The remaining 47 (15.1%) strains carried the ptxP3 allele, mainly harboring the ptxA1/ptxC2/prn2 alleles (93.6%, 44/47), and were sensitive to erythromycin (except for two strains). The two ER-ptxP3 isolates were first identified in China, belonged to MT27 and MT28 according to MLVA, and were classified into sub-lineage IVd by phylogenetic analysis of their genome sequences. This sub-lineage also includes many strains carrying the ptxP3 allele spreading in developed countries. For each tested antimicrobial, the susceptibilities judged by KB disks were consistent with those determined by E-test strips.

Conclusion: The present results reveal that B. pertussis strains with the ptxP1-ER profile still dominate in China, and a few strains carrying the ptxP3 allele have acquired the A2047G mutation in the 23S rRNA gene and the ER phenotype. The surveillance of the drug susceptibility of B. pertussis is necessary for all countries, and the KB disk method can be adopted as a screening test.

Keywords: Bordetella pertussis; erythromycin-resistance; genome sequence; molecular epidemiology; ptxp3; virulence-related genotypes.