Diagnosis of canine leptospirosis by a highly sensitive FRET-PCR targeting the lig genes

PLoS One. 2014 Feb 24;9(2):e89507. doi: 10.1371/journal.pone.0089507. eCollection 2014.

Abstract

Canine leptospirosis is underdiagnosed due to its wide spectrum of clinical presentations and the lack of a rapid and sensitive test for the accurate diagnosis of acute and chronic infections. In this study, we developed a highly sensitive and specific fluorescence resonance energy transfer (FRET)-PCR to detect common pathogenic leptospires in dogs, including Leptospira interrogans serovars Autumnalis, Canicola, Copenhageni (Icterohaemorrhagiae serogroup) and Pomona, and Leptospira kirschneri serovar Grippotyphosa. This PCR targets the lig genes, exclusively found in the pathogenic Leptospira species but not in saprophytic species (L. biflexa). A robust, high-stringency step-down real-time platform was coupled to the highly specific detection of leptospiral DNA by fluorescently labeled FRET probes. This enabled the detection of a single copy of the lig gene in a PCR containing DNA from up to 50 µL canine blood or 400 µL urine. Sensitivity determination by use of limiting serial dilutions of extracted leptospiral DNA indicated that the lig FRET-PCR we established was almost 100-fold more sensitive than the widely accepted lipL32 SYBR assay and 10-fold more sensitive than a 16S rRNA TaqMan assay. Application of this method to 207 dogs with potential leptospiral infection enabled us to diagnose three cases of canine leptospirosis characterized by low amounts of leptospiral DNA in body fluids. Detection of canine leptospirosis with the lig FRET-PCR was more sensitive with the lig FRET-PCR than with the 16S rRNA TaqMan PCR, which detected only 2 of the 3 cases, and the lipL32 SYBR PCR, which detected none of the 3 dogs with leptospirosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agglutination Tests
  • Animals
  • Base Sequence
  • DNA, Bacterial / blood
  • DNA, Bacterial / genetics
  • DNA, Bacterial / urine
  • Dog Diseases / diagnosis*
  • Dog Diseases / genetics
  • Dog Diseases / microbiology
  • Dogs
  • Fluorescence Resonance Energy Transfer / veterinary*
  • Genes, Bacterial / genetics*
  • Leptospira / genetics*
  • Leptospira / pathogenicity
  • Leptospirosis / diagnosis*
  • Leptospirosis / genetics
  • Leptospirosis / veterinary*
  • Molecular Sequence Data
  • RNA, Ribosomal, 16S / blood
  • RNA, Ribosomal, 16S / genetics
  • RNA, Ribosomal, 16S / urine
  • Real-Time Polymerase Chain Reaction / veterinary*
  • Sequence Homology, Nucleic Acid

Substances

  • DNA, Bacterial
  • RNA, Ribosomal, 16S

Grants and funding

This study was funded by the Molecular Diagnostics Laboratory at the College of Veterinary Medicine at Auburn University and by the Ross University School of Veterinary Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.