Laboratory for Infectious Diseases and Screening, Netherlands Centre for Infectious Diseases Control, RIVM, Bilthoven, Netherlands.
BMC Genomics. 2010 Nov 11;11:627. doi: 10.1186/1471-2164-11-627.
Despite vaccination since the 1950s, pertussis has persisted and resurged. It remains a major cause of infant death worldwide and is the most prevalent vaccine-preventable disease in developed countries. The resurgence of pertussis has been associated with the expansion of Bordetella pertussis strains with a novel allele for the pertussis toxin (Ptx) promoter, ptxP3, which have replaced resident ptxP1 strains. Compared to ptxP1 strains, ptxP3 produce more Ptx resulting in increased virulence and immune suppression. To elucidate how B. pertussis has adapted to vaccination, we compared genome sequences of two ptxP3 strains with four strains isolated before and after the introduction vaccination.
The distribution of SNPs in regions involved in transcription and translation suggested that changes in gene regulation play an important role in adaptation. No evidence was found for acquisition of novel genes. Modern strains differed significantly from prevaccination strains, both phylogenetically and with respect to particular alleles. The ptxP3 strains were found to have diverged recently from modern ptxP1 strains. Differences between ptxP3 and modern ptxP1 strains included SNPs in a number of pathogenicity-associated genes. Further, both gene inactivation and reactivation was observed in ptxP3 strains relative to modern ptxP1 strains.
Our work suggests that B. pertussis adapted by successive accumulation of SNPs and by gene (in)activation. In particular changes in gene regulation may have played a role in adaptation.
尽管自 20 世纪 50 年代以来已进行疫苗接种，但百日咳仍持续存在并再次爆发。它仍然是全球婴儿死亡的主要原因，也是发达国家最普遍的可通过疫苗预防的疾病。百日咳的再次爆发与具有新型百日咳毒素（Ptx）启动子（ptxP3）新型等位基因的博德特氏菌（Bordetella pertussis）菌株的扩张有关，这些新型等位基因取代了驻留的 ptxP1 菌株。与 ptxP1 菌株相比，ptxP3 菌株产生更多的 Ptx，导致毒力和免疫抑制增加。为了阐明 B. pertussis 如何适应疫苗接种，我们比较了两个 ptxP3 菌株与在引入疫苗之前和之后分离的四个菌株的基因组序列。
参与转录和翻译的区域中 SNP 的分布表明，基因调控的变化在适应中起着重要作用。没有发现获得新基因的证据。现代菌株在系统发育和特定等位基因方面与疫苗接种前的菌株明显不同。ptxP3 菌株最近从现代 ptxP1 菌株中分化出来。与现代 ptxP1 菌株相比，ptxP3 菌株和现代 ptxP1 菌株之间存在差异，包括许多与致病性相关的基因中的 SNP。此外，与现代 ptxP1 菌株相比，ptxP3 菌株中观察到基因失活和再激活。
我们的工作表明，B. pertussis 通过连续积累 SNP 和基因（失）活来适应。特别是基因调控的变化可能在适应中起作用。
