Section of Microbiology, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
FEMS Microbiol Lett. 2012 Aug;333(1):77-84. doi: 10.1111/j.1574-6968.2012.02601.x. Epub 2012 Jun 18.
In this study, two highly specific quantitative PCR assays targeting the bacterial genera Burkholderia and Pseudomonas were developed and evaluated on soil samples. The primers were targeting different multivariate regions of the 16S rRNA gene and designed to be compatible with quantitative PCR and the high throughput 454 pyrosequencing technique. The developed assays were validated using the standard methods. All tests with the new developed assays showed very high specificity. Pyrosequencing was used for direct analysis of the PCR product and applied as a specificity measurement of the primers. The Pseudomonas primers showed a 99% primer specificity, which covered 200 different Pseudomonas sequence clusters in 0.5 g of soil. In contrast to that the same approach using the genus-specific Burkholderia primers showed only 8% primer specificity. This discrepancy in primer specificity between the normal procedures compared with pyrosequencing illustrates that the common validation procedures for quantitative PCR primers may be misleading. Our results exemplify the fact that current 16S RNA gene sequence databases might lack resolution within many taxonomic groups and emphasize the necessity for a standardized and functional primer validation protocol. A possible solution to this could be to supplement the normal verification of quantitative PCR assays with a pyrosequencing approach.
在这项研究中,我们开发并评估了两种针对伯克霍尔德氏菌属和假单胞菌属的高度特异性定量 PCR 检测方法,用于土壤样本。这些引物靶向 16S rRNA 基因的不同多元区,设计用于与定量 PCR 和高通量 454 焦磷酸测序技术兼容。使用标准方法验证了所开发的检测方法。新开发的检测方法的所有测试均表现出非常高的特异性。焦磷酸测序可直接分析 PCR 产物,并用作引物特异性的测量方法。假单胞菌属引物的特异性为 99%,可覆盖 0.5 克土壤中 200 个不同的假单胞菌序列簇。相比之下,使用属特异性伯克霍尔德氏菌属引物的相同方法仅显示 8%的引物特异性。与焦磷酸测序相比,普通程序中引物特异性的这种差异表明,定量 PCR 引物的常见验证程序可能具有误导性。我们的结果说明了一个事实,即当前的 16S RNA 基因序列数据库可能在许多分类群中缺乏分辨率,并强调需要标准化和功能验证引物的协议。解决此问题的一种可能方法是,使用焦磷酸测序方法补充定量 PCR 检测的常规验证。