Genomic epidemiology and multilevel genome typing of <i>Bordetella pertussis</i>

<i>Bordetella pertussis</i> causes pertussis (or whooping cough), a severe respiratory infectious disease in infants, although it can be prevented by whole cell and acellular vaccines. The recent pertussis resurgence in industrialised countries is partly attributed to pathogen adaptation to vaccines, while emergence of antimicrobial resistance, specifically to macrolides in China, has become a concern. Surveillance of current circulating and emerging strains is therefore vital to understand the risks they pose to public health. Although the use of genomics-based typing is increasing a genomic nomenclature for this pathogen has not been well established. Here, we implemented the multilevel genome typing (MGT) system for <i>B. pertussis</i> with five levels of resolution, which provide targeted typing of relevant lineages and discrimination of closely related strains at the finest scale. The lower resolution levels (MGT2 and MGT3) describe the distribution of major vaccine antigen alleles including <i>ptxP</i>, <i>fim3, fhaB</i> and <i>prn,</i> as well as temporal and spatial trends within the <i>B. pertussis</i> global population. Mid-resolution levels (MGT3 and MGT4) enable typing of antibiotic-resistant lineages and Prn deficient lineages within the <i>ptxP3</i> clade. The high-resolution level (MGT5) can capture finer-scale epidemiology such as outbreaks and local transmission events, with comparable resolution to existing genomic methods of strain-relatedness assessment. The scheme offers stable MGT-type assignments aiding harmonisation of typing and communication between laboratories. The scheme is available at https://mgtdb.unsw.edu.au/pertussis, is regularly updated from global data repositories and accepts public submissions. The MGT scheme provides a comprehensive, robust, and scalable system for global surveillance of <i>B. pertussis</i>.百日咳博德特菌（*Bordetella pertussis*）可引发百日咳（又称哮咳），是一种累及婴儿的严重呼吸道传染病，虽可通过全细胞疫苗与无细胞疫苗实现有效预防。近年来工业化国家出现百日咳疫情反弹，部分源于病原体对疫苗的适应性；而抗菌药物耐药性（尤其是中国境内针对大环内酯类的耐药性）已成为公共卫生领域的新关注点。因此，对当前流行与新发菌株开展监测，对于明确其对公众健康构成的风险至关重要。尽管基于基因组学的分型技术应用愈发广泛，但针对该病原体的基因组分型命名体系仍未得到充分建立。本研究针对百日咳博德特菌构建了一套五级分辨率的多级基因组分型（multilevel genome typing, MGT）体系，该体系可针对相关谱系实现靶向分型，并在最高分辨率级别下区分亲缘关系紧密的菌株。低分辨率级别（MGT2与MGT3）可涵盖主要疫苗抗原等位基因的分布特征，包括*ptxP*、*fim3*、*fhaB*及*prn*，同时可反映百日咳博德特菌全球种群的时间与空间流行趋势。中分辨率级别（MGT3与MGT4）可实现对*ptxP3*进化支内的耐药谱系与Prn缺陷谱系进行分型。高分辨率级别（MGT5）可捕捉更精细尺度的流行病学特征，例如暴发疫情与本地传播事件，其分辨率可与现有用于菌株相关性评估的基因组学方法相媲美。该分型体系可提供稳定的MGT型别赋值，有助于实现实验室间分型工作的标准化与结果沟通。该体系可通过https://mgtdb.unsw.edu.au/pertussis获取，其数据定期从全球数据仓库更新，并接受公众提交的相关数据。本研究构建的MGT体系为百日咳博德特菌的全球监测提供了一套全面、稳健且可扩展的技术方案。