Intracellular localisation of Mycobacterium tuberculosis affects efficacy of the antibiotic pyrazinamide.

ABSTRACT: To be effective, chemotherapy against tuberculosis (TB) must kill the intracellular population of the pathogen, Mycobacterium tuberculosis. However, how host cell microenvironments affect antibiotic accumulation and efficacy remains unclear. Here, we use correlative light, electron, and ion microscopy to investigate how various microenvironments within human macrophages affect the activity of pyrazinamide (PZA), a key antibiotic against TB. We show that PZA accumulates heterogeneously among individual bacteria in multiple host cell environments. Crucially, PZA accumulation and efficacy is maximal within acidified phagosomes. Bedaquiline, another antibiotic commonly used in combined TB therapy, enhances PZA accumulation via a host cell-mediated mechanism. Thus, intracellular localisation an

SUBMITTER: Santucci P 

PROVIDER: S-EPMC8217510 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature