Bordetella diversity project

“Global population structure and evolution of Bordetella pertussis and their relationship with vaccination.” Pubmed ID: 24757216. Bordetella pertussis causes pertussis, a respiratory disease that is most severe for infants. Vaccination was introduced in the 1950s, and in recent years, a resurgence of disease was observed worldwide, with significant mortality in infants. Possible causes for this include the switch from whole-cell vaccines (WCVs) to less effective acellular vaccines (ACVs), waning immunity, and pathogen adaptation. Pathogen adaptation is suggested by antigenic divergence between vaccine strains and circulating strains and by the emergence of strains with increased pertussis toxin production. We applied comparative genomics to a worldwide collection of 343 B. pertussis strains isolated between 1920 and 2010. The global phylogeny showed two deep branches; the largest of these contained 98% of all strains, and its expansion correlated temporally with the first descriptions of pertussis outbreaks in Europe in the 16th century. We found little evidence of recent geographical clustering of the strains within this lineage, suggesting rapid strain flow between countries. We observed that changes in genes encoding proteins implicated in protective immunity that are included in ACVs occurred after the introduction of WCVs but before the switch to ACVs. Furthermore, our analyses consistently suggested that virulence-associated genes and genes coding for surface-exposed proteins were involved in adaptation. However, many of the putative adaptive loci identified have a physiological role, and further studies of these loci may reveal less obvious ways in which B. pertussis and the host interact. This work provides insight into ways in which pathogens may adapt to vaccination and suggests ways to improve pertussis vaccines. Whooping cough is mainly caused by Bordetella pertussis, and current vaccines are targeted against this organism. Recently, there have been increasing outbreaks of whooping cough, even where vaccine coverage is high. Analysis of the genomes of 343 B. pertussis isolates from around the world over the last 100 years suggests that the organism has emerged within the last 500 years, consistent with historical records. We show that global transmission of new strains is very rapid and that the worldwide population of B. pertussis is evolving in response to vaccine introduction, potentially enabling vaccine escape.

本研究主题为《百日咳博德特氏菌（Bordetella pertussis）的全球种群结构、演化及其与疫苗接种的关联》，其PubMed编号为24757216。百日咳博德特氏菌可引发百日咳——一种对婴儿危害最为严重的呼吸道传染病。疫苗接种于20世纪50年代投入使用，而近年来全球范围内出现了百日咳疫情反弹，造成婴儿出现显著死亡病例。此次疫情反弹的潜在诱因包括：从全细胞疫苗（WCVs）转向保护效力更弱的无细胞疫苗（ACVs）、免疫力衰减，以及病原体适应性演化。疫苗株与流行株之间的抗原差异、百日咳毒素产量升高的菌株出现，均提示病原体发生了适应性演化。
本研究对1920年至2010年间分离自全球的343株百日咳博德特氏菌进行了比较基因组学分析。全球系统发育分析显示存在两个深度分支；其中最大的分支涵盖了98%的受试菌株，该分支的扩张时间与16世纪欧洲首次报道百日咳暴发的时间存在时间相关性。本研究未发现该谱系内菌株存在近期地理聚集的证据，提示菌株在各国间传播速度较快。我们观察到，无细胞疫苗（ACVs）所包含的、与保护性免疫相关的编码蛋白基因的变异，发生于全细胞疫苗（WCVs）引入之后、转向无细胞疫苗（ACVs）之前。
此外，本研究分析一致表明，毒力相关基因以及编码表面暴露蛋白的基因参与了病原体的适应性演化过程。但本研究鉴定出的诸多潜在适应性位点均具有生理功能，针对这些位点的后续研究或可揭示百日咳博德特氏菌与宿主之间此前未被发现的互作方式。本研究为病原体如何适应疫苗接种压力提供了新的见解，并为百日咳疫苗的优化方向提供了参考。
百日咳主要由百日咳博德特氏菌引发，当前的疫苗均以该病原菌为靶点。即便在疫苗接种覆盖率较高的地区，近年来百日咳暴发的报告也呈上升趋势。对过去100年间全球范围内分离得到的343株百日咳博德特氏菌进行基因组分析的结果显示，该病原菌在近500年内才出现演化，这与历史记录相符。我们的研究结果表明，新型菌株的全球传播速度极快，而百日咳博德特氏菌的全球种群正随着疫苗接种的推行不断演化，这可能使其获得疫苗逃逸能力。