An in vivo biosafety-level-2-compatible model of Mycobacterium tuberculosis infection for drug susceptibility testing

STAR Protoc. 2022 Jul 19;3(3):101575. doi: 10.1016/j.xpro.2022.101575. eCollection 2022 Sep 16.

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).

Keywords: Cell Biology; Cell-based Assays; Flow Cytometry/Mass Cytometry; Immunology; Microbiology; Model Organisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Containment of Biohazards
  • Mice
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis* / genetics
  • Pharmaceutical Preparations
  • Tuberculosis, Lymph Node*

Substances

  • Pharmaceutical Preparations

Grants and funding