The development and use of Actiphage® to detect viable mycobacteria from bovine tuberculosis and Johne's disease-infected animals

Microb Biotechnol. 2020 May;13(3):738-746. doi: 10.1111/1751-7915.13518. Epub 2019 Dec 3.

Abstract

Here, we describe the development of a method that exploits bacteriophage D29 as a lysis agent for efficient DNA extraction from low numbers of mycobacterial cells. This method (Actiphage® ) used in combination with PCR achieved rapid and sensitive (LOD ≤ 10 cell ml-1 ) detection and identification of viable, pathogenic mycobacteria in blood samples within 6 h. We demonstrate that mycobacteriophage D29 can be used to detect a range of mycobacteria from clinical blood samples including both Mycobacterium tuberculosis complex and Mycobacterium avium subsp. paratuberculosis without the need for culture and confirms our earlier observations that a low-level bacteraemia is associated with these infections in cattle. In a study of M. bovis-infected cattle (n = 41), the sensitivity of the Actiphage® method was 95 % (95 % CI; 0.84-0.99) and specificity was 100 % (95% CI; 0.92-1). We further used Actiphage® to demonstrate viable Mycobacterium avium subsp. paratuberculosis is present in the blood of Johne's infected cattle. This method provides a revolutionary new tool for the study of infections caused by these difficult to grow pathogens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteriophages* / metabolism
  • Cattle
  • Cattle Diseases* / diagnosis
  • Molecular Diagnostic Techniques* / methods
  • Molecular Diagnostic Techniques* / veterinary
  • Mycobacterium avium subsp. paratuberculosis* / genetics
  • Paratuberculosis* / diagnosis
  • Paratuberculosis* / microbiology
  • Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Tuberculosis, Bovine* / diagnosis
  • Tuberculosis, Bovine* / microbiology