Genotypic Variation in the Bordetella pertussis Virulence Factors Pertactin and Pertussis Toxin in Historical and Recent Clinical Isolates in the United Kingdom

The reemergence of pertussis has been reported in several countries despite high vaccination coverage. Studies in The Netherlands and Finland have investigated polymorphism in the genes coding for two important virulence factors of Bordetella pertussis, pertactin and pertussis toxin, and identified the emergence and subsequent dominance in circulating strains of pertactin and toxin variants not found in the whole-cell vaccine (WCV). The study described here investigated whether such variation had occurred in the United Kingdom, which presently has low levels of pertussis. Sequence analysis of the genes for pertactin (prnA) and the pertussis toxin S1 subunit (ptxA) among isolates of B. pertussis from 285 United Kingdom patients, from 1920 to 1999, revealed three prnA variants, prnA(1), prnA(2), and prnA(3), and two ptxA variants, ptxA(1) and ptxA(2), showing differences in nucleic acid sequence. The proportion of pertactin gene types not included in the United Kingdom WCV, i.e., prnA(2) and prnA(3), has increased in recent years and was found in 21 of 86 (24%) strains from the 1980s and 56 of 105 (53%) strains from the 1990s. To date, the presence of these nonvaccine prnA types has not been associated with a resurgence of pertussis in the United Kingdom. The distribution of prnA and ptxA types in The Netherlands, Finland, and the United Kingdom in the 1990s is distinct. The most striking difference in the United Kingdom isolates is that all 105 of the most recent circulating strains (from 1998 to 1999) are of a pertussis toxin type found in the United Kingdom WCV, i.e., ptxA(1).

尽管百日咳（pertussis）疫苗接种覆盖率较高，多个国家仍有百日咳复现的报道。荷兰与芬兰的相关研究针对编码百日咳博德特菌（Bordetella pertussis）两种重要毒力因子的基因——百日咳黏附素（pertactin）与百日咳毒素（pertussis toxin）——开展了多态性分析，结果发现循环菌株中出现了全细胞百日咳疫苗（whole-cell vaccine, WCV）未覆盖的百日咳黏附素与毒素变异株，且此类变异株逐渐成为优势流行菌株。本研究旨在探究当前百日咳发病率处于较低水平的英国是否也存在此类基因变异情况。研究人员对1920年至1999年间来自285名英国患者的百日咳博德特菌分离株开展了百日咳黏附素基因（prnA）与百日咳毒素S1亚基基因（ptxA）的序列分析，共检出3种prnA变异型（prnA(1)、prnA(2)与prnA(3)）以及2种ptxA变异型（ptxA(1)与ptxA(2)），各变异型间核酸序列存在显著差异。未被英国全细胞百日咳疫苗覆盖的prnA变异型（即prnA(2)与prnA(3)）的占比近年来呈上升趋势：20世纪80年代的86株分离株中，该类变异型占比为24%（21/86）；90年代的105株分离株中占比升至53%（56/105）。截至目前，这类非疫苗型prnA变异株尚未与英国百日咳的复现存在关联。20世纪90年代，荷兰、芬兰与英国的prnA及ptxA变异型分布存在显著差异。英国分离株最显著的差异在于：1998年至1999年的105株最新循环菌株均属于英国全细胞百日咳疫苗覆盖的百日咳毒素型——即ptxA(1)。