Misawa N, Allos B M, Blaser M J
Division of Infectious Diseases, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2605, USA.
J Clin Microbiol. 1998 Dec;36(12):3567-73. doi: 10.1128/JCM.36.12.3567-3573.1998.
Guillain-Barré syndrome (GBS), a neurologic disease characterized by acute paralysis, is frequently preceded by Campylobacter jejuni infection. Serotype O19 strains are overrepresented among GBS-associated C. jejuni isolates. We previously showed that all O19 strains tested were closely related to one another by randomly amplified polymorphic DNA (RAPD) and restriction fragment length polymorphism analyses. RAPD analysis demonstrated a 1.4-kb band in all O19 strains tested but in no non-O19 strains. We cloned this O19-specific band; nucleotide sequence analysis revealed a truncated open reading frame with significant homology to DNA gyrase subunit B (gyrB) of Helicobacter pylori. PCR using the random primer and a primer specific for gyrB showed that in non-O19 strains, the random primer did not recognize the downstream gyrB binding site. The regions flanking each of the random primer binding sites were amplified by degenerate PCR for further sequencing. Although the random primer had several mismatches with the downstream gyrB binding site, a single nucleotide polymorphism 6 bp upstream from the 3' terminus was found to distinguish O19 and non-O19 strains. PCR using 3'-mismatched primers based on this polymorphism was designed to differentiate O19 strains from non-O19 strains. When a total of 42 (18 O19 and 24 non-O19) strains from five different countries were examined, O19 strains were distinguishable from non-O19 strains in each case. This PCR method should permit identification of O19 C. jejuni strains.
吉兰 - 巴雷综合征(GBS)是一种以急性瘫痪为特征的神经系统疾病,通常在空肠弯曲菌感染后出现。血清型O19菌株在与GBS相关的空肠弯曲菌分离株中占比过高。我们之前通过随机扩增多态性DNA(RAPD)和限制性片段长度多态性分析表明,所有测试的O19菌株彼此密切相关。RAPD分析显示,所有测试的O19菌株中都有一条1.4kb的条带,而在非O19菌株中则没有。我们克隆了这条O19特异性条带;核苷酸序列分析揭示了一个截短的开放阅读框,与幽门螺杆菌的DNA促旋酶亚基B(gyrB)具有显著同源性。使用随机引物和gyrB特异性引物进行PCR分析表明,在非O19菌株中,随机引物无法识别下游gyrB结合位点。通过简并PCR扩增随机引物结合位点两侧的区域以进行进一步测序。尽管随机引物与下游gyrB结合位点存在多处错配,但在3'末端上游6bp处发现了一个单核苷酸多态性,可区分O19和非O19菌株。基于这种多态性设计了使用3'错配引物的PCR方法,以区分O19菌株和非O19菌株。当检测来自五个不同国家的总共42株菌株(18株O19和24株非O19)时,在每种情况下O19菌株都可与非O19菌株区分开来。这种PCR方法应该能够鉴定O19空肠弯曲菌菌株。