Department of Infectious Disease Surveillance and Control, National Institute for Health and Welfare, Kiinamyllynkatu 13, 20520 Turku, Finland.
Infect Genet Evol. 2011 Dec;11(8):2034-42. doi: 10.1016/j.meegid.2011.09.012. Epub 2011 Sep 21.
Resurgence of pertussis has been observed in many countries with high vaccination coverage and clonal expansion of certain Bordetella pertussis strains has been associated with recent epidemics in Europe. It is known that vaccinations have selected strains which are different from those used for vaccine production. However, little is known about the differences in genomic content of strains circulating before the vaccination was introduced. In this study, we compared the genomes of 39 vaccine strains and old clinical isolates (isolated 1941-1984) collected from Finland (n = 5), Poland (n = 14), Serbia (n = 10) and the UK (n = 10). The analysis included genotyping, pulsed-field gel electrophoresis (PFGE) and comparative genomic hybridisation (CGH). Compared to the strain Tohama I, the European isolates analyzed have lost three major regions of difference (RD3, 5 and 29). However, difference in frequency of the absent RDs 3 (BP0910A-BP0934), 5 (BP1135-BP1141) or 29 (BP1225) was observed among isolates from the four countries. Of the isolates with absent RD5, half had also a duplicated region in the genome. All four RDs (RD22 (BB0535-BB0541), 23 (BB0916-BB0921), 24 (BB1140-BB1158) and 26 (BB4880-BB4888)) absent in Tohama I were present in majority of the tested isolates. Results obtained from PFGE analysis correlated well with those of CGH. Recently a novel pertussis toxin promoter allele (ptxP3) was described. Isolates with ptxP3 have replaced resident ptxP1 isolates in the countries where this was investigated. When the recent isolates, collected in 2000-2004, selected from the four countries were examined, the ptxP3 allele was found in all countries except Poland. Our result indicates that at least three clusters of B. pertussis circulated in Europe in pre- and early vaccine era and their genomes were distinct from that of the reference strain Tohama I. Although progressive gene loss occurs in B. pertussis population with time, difference in frequency of the lost genes were observed among isolates from the four countries. The observed differences in genomic content might be vaccine-driven.
百日咳在许多高疫苗覆盖率的国家再次出现，某些博德特氏菌百日咳菌株的克隆扩张与欧洲最近的流行有关。众所周知，疫苗接种选择了与疫苗生产所用菌株不同的菌株。然而，对于接种疫苗引入之前流行菌株的基因组内容差异知之甚少。在这项研究中，我们比较了来自芬兰（n=5）、波兰（n=14）、塞尔维亚（n=10）和英国（n=10）的 39 株疫苗株和旧临床分离株（1941-1984 年分离）的基因组。分析包括基因分型、脉冲场凝胶电泳（PFGE）和比较基因组杂交（CGH）。与 Tohama I 株相比，分析的欧洲分离株失去了三个主要差异区（RD3、5 和 29）。然而，在来自四个国家的分离株中观察到缺失 RD3（BP0910A-BP0934）、5（BP1135-BP1141）或 29（BP1225）的频率存在差异。在缺失 RD5 的分离株中，有一半的基因组中也存在一个重复区域。在测试的分离株中，四个 RD（RD22（BB0535-BB0541）、23（BB0916-BB0921）、24（BB1140-BB1158）和 26（BB4880-BB4888））都不存在于 Tohama I 株中。最近描述了一种新的百日咳毒素启动子等位基因（ptxP3）。在进行调查的国家中，具有 ptxP3 的分离株已取代了常驻 ptxP1 分离株。当从 2000-2004 年在四个国家收集的最近分离株进行检查时，除波兰外，所有国家都发现了 ptxP3 等位基因。我们的结果表明，在疫苗前和早期疫苗时代，至少有三个博德特氏菌群在欧洲流行，它们的基因组与参考株 Tohama I 不同。尽管随着时间的推移，博德特氏菌种群中会发生基因逐渐丢失，但在来自四个国家的分离株中观察到丢失基因的频率存在差异。观察到的基因组内容差异可能是由疫苗驱动的。
