Over the last 20 year we have been exploiting a broad host range, lytic phage (D29) as a DNA lysing agent to develop rapid and sensitive tests to detect and identify mycobacterial pathogens. In addition to being very efficient at lysing mycobacteria, phage have another advantage over chemical extraction methods when used as part of DNA-detection tests in that only viable cells are lysed, and therefore successful lysis using phage also reports on the viability of the cell detected. We have now developed a method that can successfully detect mycobacteria within 6 h, which has been commercialised as Actiphage test. During these studies we have discovered new features of the phage-host interaction that has allowed us to better understand and improve our test methods and have shown that the method can be used to diagnose mycobacterial infections in a range of animals, including exotic species such as lions and elephants.

However, for any new biotech product to flourish, there has to be a commercial market, so more recently we have shown that Actiphage can be used to detect TB in human blood. Using phage D29, which, only efficiently infects metabolically active Mycobacterium tuberculosis (Mtb), an initial proof of principle study found viable Mtb can be detected in peripheral white blood cells isolated from patients with active pulmonary TB in immunocompetent patients (Sn = 73%; Sp = 100%). Positive phage assay results were associated with a range of other clinical indications of infection, suggesting that low-grade, bacterial dissemination is a feature of poorly controlled disease and occurs more commonly than has been generally reported in this group. In a second, follow up, prospective study focussing on identifying progressive infection in asymptomatic pulmonary TB contacts, we have recently found  evidence for a detectable bacteraemia in earlier stages of progressive TB infection.  

This talk will review what we have learned about phage host interactions during the development of Actiphage, and outline how we are now adapting this method to ask new questions.  Once again phage have been shown to be an invaluable tool to reveal new things about their host cells.

"The real voyage of discovery consists not in seeking new landscapes, but in having new eyes" Marcel Proust, (1871-1922)

 Swift et al. (2020) The development and use of Actiphage® to detect viable mycobacteria from bovine tuberculosis and Johne’s disease‐infected animals. Microb Biotechnol.  13:738– 746 doi: 10.1111/1751-7915.13518

 Verma et al. (2020) An, high-sensitivity, bacteriophage-based assay identifies low-level Mycobacterium tuberculosis bacteremia in immunocompetent patients with active and incipient Tuberculosis. Clin Infect Dis, ciz548, doi: 10.1093/cid/ciz548