Howell Kate J, Peters Sarah E, Wang Jinhong, Hernandez-Garcia Juan, Weinert Lucy A, Luan Shi-Lu, Chaudhuri Roy R, Angen Øystein, Aragon Virginia, Williamson Susanna M, Parkhill Julian, Langford Paul R, Rycroft Andrew N, Wren Brendan W, Maskell Duncan J, Tucker Alexander W
Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom
Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
J Clin Microbiol. 2015 Dec;53(12):3812-21. doi: 10.1128/JCM.01991-15. Epub 2015 Sep 30.
Haemophilus parasuis causes Glässer's disease and pneumonia in pigs. Indirect hemagglutination (IHA) is typically used to serotype this bacterium, distinguishing 15 serovars with some nontypeable isolates. The capsule loci of the 15 reference strains have been annotated, and significant genetic variation was identified between serovars, with the exception of serovars 5 and 12. A capsule locus and in silico serovar were identified for all but two nontypeable isolates in our collection of >200 isolates. Here, we describe the development of a multiplex PCR, based on variation within the capsule loci of the 15 serovars of H. parasuis, for rapid molecular serotyping. The multiplex PCR (mPCR) distinguished between all previously described serovars except 5 and 12, which were detected by the same pair of primers. The detection limit of the mPCR was 4.29 × 10(5) ng/μl bacterial genomic DNA, and high specificity was indicated by the absence of reactivity against closely related commensal Pasteurellaceae and other bacterial pathogens of pigs. A subset of 150 isolates from a previously sequenced H. parasuis collection was used to validate the mPCR with 100% accuracy compared to the in silico results. In addition, the two in silico-nontypeable isolates were typeable using the mPCR. A further 84 isolates were analyzed by mPCR and compared to the IHA serotyping results with 90% concordance (excluding those that were nontypeable by IHA). The mPCR was faster, more sensitive, and more specific than IHA, enabling the differentiation of 14 of the 15 serovars of H. parasuis.
副猪嗜血杆菌可引起猪的格拉泽氏病和肺炎。间接血凝试验(IHA)通常用于对该细菌进行血清分型,可区分出15个血清型以及一些不可分型的分离株。已对15个参考菌株的荚膜基因座进行了注释,除血清型5和12外,各血清型之间存在显著的遗传变异。在我们收集的200多个分离株中,除两个不可分型的分离株外,其余所有分离株均鉴定出了荚膜基因座和计算机模拟血清型。在此,我们描述了一种基于副猪嗜血杆菌15个血清型荚膜基因座变异的多重PCR方法的开发,用于快速分子血清分型。该多重PCR(mPCR)可区分除血清型5和12之外的所有先前描述的血清型,血清型5和12由同一对引物检测。mPCR的检测限为4.29×10⁵ ng/μl细菌基因组DNA,对密切相关的共生巴斯德氏菌科和猪的其他细菌病原体无反应性,表明其具有高特异性。与计算机模拟结果相比,从先前测序的副猪嗜血杆菌集合中选取的150个分离株的子集用于验证mPCR,准确率达100%。此外,这两个计算机模拟不可分型的分离株也可用mPCR进行分型。另外对84个分离株进行了mPCR分析,并与IHA血清分型结果进行比较,一致性达90%(不包括IHA不可分型的那些)。mPCR比IHA更快、更灵敏、更特异,能够区分副猪嗜血杆菌15个血清型中的14个。