Pyrosequencing-based validation of a simple cell-suspension polymerase chain reaction assay for Campylobacter with application of high-processivity polymerase and novel internal amplification controls for rapid and specific detection

Diagn Microbiol Infect Dis. 2012 Feb;72(2):131-8. doi: 10.1016/j.diagmicrobio.2011.11.001.

Abstract

Although Campylobacter is an important food-borne human pathogen, there remains a lack of molecular diagnostic assays that are simple to use, cost-effective, and provide rapid results in research, clinical, or regulatory laboratories. Of the numerous Campylobacter assays that do exist, to our knowledge none has been empirically tested for specificity using high-throughput sequencing. Here we demonstrate the power of next-generation sequencing to determine the specificity of a widely cited Campylobacter-specific polymerase chain reaction (PCR) assay and describe a rapid method for direct cell suspension PCR to quickly and easily screen samples for Campylobacter. We present a specific protocol which eliminates the need for time-consuming and expensive genomic DNA extractions and, using a high-processivity polymerase, demonstrate conclusive screening of samples in <1 h. Pyrosequencing results show the assay to be extremely (>99%) sensitive, and spike-back experiments demonstrated a detection threshold of <10(2) CFU mL(-1). Additionally, we present 2 newly designed broad-range bacterial primer sets targeting the 23S rRNA gene that have wide applicability as internal amplification controls. Empirical testing of putative taxon-specific assays using high-throughput sequencing is an important validation step that is now financially feasible for research, regulatory, or clinical applications.

Publication types

  • Validation Study

MeSH terms

  • Campylobacter / classification
  • Campylobacter / genetics
  • Campylobacter / isolation & purification*
  • DNA-Directed DNA Polymerase / classification*
  • Phylogeny
  • Polymerase Chain Reaction / methods*
  • Polymerase Chain Reaction / standards
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Time Factors

Substances

  • DNA-Directed DNA Polymerase