Fredricks D N, Relman D A
Department of Medicine, Division of Infectious Diseases, Stanford University Medical Center, Stanford, California 94305, USA.
J Clin Microbiol. 1998 Oct;36(10):2810-6. doi: 10.1128/JCM.36.10.2810-2816.1998.
Molecular methods are increasingly used to identify microbes in clinical samples. A common technical problem with PCR is failed amplification due to the presence of PCR inhibitors. Initial attempts at amplification of the bacterial 16S rRNA gene from inoculated blood culture media failed for this reason. The inhibitor persisted, despite numerous attempts to purify the DNA, and was identified as sodium polyanetholesulfonate (SPS), a common additive to blood culture media. Like DNA, SPS is a high-molecular-weight polyanion that is soluble in water but insoluble in alcohol. Accordingly, SPS tends to copurify with DNA. An extraction method was designed for purification of DNA from blood culture media and removal of SPS. Blood culture media containing human blood and spiked with Escherichia coli was subjected to an organic extraction procedure with benzyl alcohol, and removal of SPS was documented spectrophotometrically. Successful amplification of the extracted E. coli 16S rRNA gene was achieved by adding 5 microliter of undiluted processed sample DNA to a 50-microliter PCR mixture. When using other purification methods, the inhibitory effect of SPS could be overcome only by dilution of these samples. By our extraction technique, even uninoculated blood culture media were found to contain bacterial DNA when they were subjected to broad-range 16S rRNA gene consensus PCR. We conclude that the blood culture additive SPS is a potent inhibitor of PCR, is resistant to removal by traditional DNA purification methods, but can be removed by a benzyl alcohol extraction protocol that results in improved PCR performance.
分子方法越来越多地用于鉴定临床样本中的微生物。聚合酶链反应(PCR)的一个常见技术问题是由于存在PCR抑制剂而导致扩增失败。由于这个原因,最初从接种的血培养培养基中扩增细菌16S rRNA基因的尝试失败了。尽管多次尝试纯化DNA,但抑制剂仍然存在,并且被鉴定为聚茴香脑磺酸钠(SPS),这是血培养培养基中常用的添加剂。与DNA一样,SPS是一种高分子量的聚阴离子,可溶于水但不溶于醇。因此,SPS倾向于与DNA共纯化。设计了一种从血培养培养基中纯化DNA并去除SPS的提取方法。将含有人类血液并接种大肠杆菌的血培养培养基用苯甲醇进行有机提取程序,并通过分光光度法记录SPS的去除情况。通过向50微升PCR混合物中加入5微升未稀释的处理后样品DNA,成功扩增了提取的大肠杆菌16S rRNA基因。当使用其他纯化方法时,只有通过稀释这些样品才能克服SPS的抑制作用。通过我们的提取技术,当对未接种的血培养培养基进行广谱16S rRNA基因共识PCR时,发现它们甚至含有细菌DNA。我们得出结论,血培养添加剂SPS是一种有效的PCR抑制剂,对传统DNA纯化方法的去除具有抗性,但可以通过苯甲醇提取方案去除,从而提高PCR性能。