Genomic epidemiology and evolution of <i>Bordetella pertussis</i> under the vaccination pressure of acellular vaccines in Beijing, China, 2020-2023

Pertussis (or whooping cough) has experienced a global resurgence despite widespread vaccine efforts. In China, the incidence of pertussis has rapidly increased, particularly following the COVID-19 pandemic. Whole-genome sequencing analysis was performed on 60 <i>Bordetella pertussis</i> strains isolated in Beijing from 2020 to 2023, and the sequences were compared with those of 635 strains from China and 943 strains from other countries. In this study, the genetic evolution of <i>B. pertussis</i> was investigated, focusing on key virulence genes (<i>ptxP</i>, <i>ptxA</i>, <i>prn</i>, <i>fim2</i>, <i>fim3</i>, <i>tcfA</i>) and the resistance-related locus A2047 across different periods and regions. The dominant antigen genotype among the 60 isolates was <i>ptxP3</i>/<i>prn2</i>/<i>ptxA1</i>/<i>fim2-1</i>/<i>fim3-1</i>/<i>tcfA2</i> (88.3%), differing from the prevalent genotype <i>ptxP-1/prn-1/ptxA-1</i> in Beijing prior to 2019 and the vaccine strain genotype <i>ptxP-1</i>/<i>prn-1</i>/<i>ptxA-2</i>/<i>fim2-1</i>/<i>fim3-1</i>/<i>tcfA2</i>. Evolutionary analysis revealed significant genetic shifts associated with the introduction of vaccines, particularly acellular vaccines. Initially, the prevalent genotypes included <i>ptxP-1</i>, <i>prn-1</i>, <i>ptxA-2</i>, <i>fim2-2</i>, and <i>fim3-2</i>. However, currently, <i>ptxP-3</i>, <i>prn-2</i> and <i>ptxA-1</i> have become predominant globally, indicating vaccine-induced selection pressure. Additionally, all 60 isolated strains (100%) presented the A2047G mutation associated with erythromycin resistance, of which <i>ptxP3</i> accounted for 91.7%. Macrolide-resistant <i>Bordetella pertussis</i> (MRBP) is widespread in China, and the prevalence of <i>ptxP3-</i>MRBP may be increasing. The significant changes of dominance of subtypes in Beijing in recent years underscore the need for continuous surveillance and adaptation of pertussis vaccination strategies.

尽管全球范围内广泛推行疫苗接种策略，百日咳（Pertussis）仍出现了全球性的复燃态势。在中国，百日咳的发病率亦显著升高，尤其是在新型冠状病毒感染（COVID-19）大流行之后。本研究对2020年至2023年期间在北京分离得到的60株百日咳鲍特菌（*Bordetella pertussis*）进行了全基因组测序分析，并将这些序列与来自中国的635株菌株以及来自其他国家的943株菌株的序列进行了比对。本研究针对不同时期与不同地域的百日咳鲍特菌（*B. pertussis*）开展遗传演化分析，重点聚焦其关键毒力基因（*ptxP*、*ptxA*、*prn*、*fim2*、*fim3*、*tcfA*）以及与耐药性相关的A2047位点。在这60株分离菌株中，优势抗原基因型为*ptxP3*/*prn2*/*ptxA1*/*fim2-1*/*fim3-1*/*tcfA2*（占比88.3%），该基因型与2019年之前北京地区流行的*ptxP-1*/*prn-1*/*ptxA-1*基因型以及疫苗株基因型*ptxP-1*/*prn-1*/*ptxA-2*/*fim2-1*/*fim3-1*/*tcfA2*均存在显著差异。演化分析结果显示，疫苗（尤其是无细胞疫苗）的引入与百日咳鲍特菌的显著遗传漂移存在关联。早期流行的基因型包括*ptxP-1*、*prn-1*、*ptxA-2*、*fim2-2*以及*fim3-2*。但目前*ptxP-3*、*prn-2*与*ptxA-1*已成为全球范围内的优势基因型，这提示疫苗诱导的选择压力正在发挥作用。此外，全部60株分离菌株（100%）均携带与红霉素耐药相关的A2047G突变，其中携带*ptxP3*基因型的菌株占比达91.7%。大环内酯类耐药百日咳鲍特菌（Macrolide-resistant *Bordetella pertussis*, MRBP）在中国分布广泛，且*ptxP3*-MRBP的流行率可能呈上升趋势。近年来北京地区百日咳鲍特菌优势亚型的显著变化，凸显了持续开展监测并优化百日咳疫苗接种策略的必要性。