An in vivo biosafety-level-2-compatible model of Mycobacterium tuberculosis infection for drug susceptibility testing
Yi Chu Liang, Stefania Berton, Courtney Reeks, Jim Sun
Abstract
Available mouse models for tuberculosis drug susceptibility testing requires using virulent biosafety-level-3 (BSL-3) Mycobacterium tuberculosis (Mtb) strains, or attenuated BSL-2 strains that lack virulence genes. Here, we present a BSL-2-compatible mouse model for tuberculosis drug susceptibility testing using the auxotrophic Mtb mc26206 strain, which retains all virulence genes. Using rifampicin and a new autophagy-boosting compound, SMIP-30, we provide a step-by-step guide for the infection, drug administration, and evaluation of Mtb burden and cytokine profiles. This protocol is easily adaptable for testing of other antibiotics and host-directed compounds. For complete details on the use and execution of this protocol, please refer to Berton et al. (2022).