Nanoluciferase Reporter Mycobacteriophage for Sensitive and Rapid Detection of Mycobacterium tuberculosis Drug Susceptibility
Paras Jain, Spencer Garing, Deepshikha Verma, Rajagopalan Saranathan, Nicholas Clute-Reinig, Jacob Gadwa, Chelsea Peterson, Gleda Hermansky, Anna Astashkina Fernandez, Emmanuel Asare, Torin R. Weisbrod, Ethan Spencer, Claire V. Mulholland, Michael Berney, David Bell, Kevin P. Nichols, Anne-Laure M. Le Ny, Diane Ordway, William R. Jacobs, Ákos Somoskövi, K Minch
Abstract
Mycobacterium tuberculosis , the causative agent of tuberculosis disease, remains a public health crisis on a global scale, and development of new interventions and identification of drug resistance are pillars in the World Health Organization End TB Strategy. Leveraging the tractability of the TM4 mycobacteriophage and the sensitivity of the nanoluciferase reporter enzyme, the present work describes an evolution of phage-mediated detection and drug susceptibility testing of M. tuberculosis , adding a valuable tool in drug discovery and basic biology research. With additional validation, this system may play a role as a quantitative phenotypic reference method and complement to genotypic methods for diagnosis and antibiotic susceptibility testing.