Antituberculous drugs modulate bacterial phagolysosome avoidance and autophagy in Mycobacterium tuberculosis-infected macrophages - Archive ouverte HAL Access content directly
Journal Articles Tuberculosis Year : 2018

Antituberculous drugs modulate bacterial phagolysosome avoidance and autophagy in Mycobacterium tuberculosis-infected macrophages

Abstract

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) complex remains a deadly infectious disease worldwide. Mtb is an intracellular pathogen, and autophagy is an essential component of the immune response leading to TB clearance. Anti-TB treatment is based on classical isoniazid (INH) and rifampicin (RIF), but also new drugs, such as linezolid (LNZ) and bedaquiline (BDQ). However, little is known about these antibiotics' impact on Mtb intra-macrophagic behavior independent of their impact on host cells. We explored the effect of mycobacterial pre-treatment with these four antibiotics on the intra-macrophagic Mtb survival and trafficking, thanks to bacterial counts and microscopy confocal imaging. Our results showed that INH and BDQ impaired Mtb phagosome escape, RIF increased autolysosome formation, and LNZ and BDQ improved autophagy activation and efficacy. These data suggest that antibiotics favoring autophagy activation (LNZ and BDQ) may allowed better Mtb clearance by macrophages and could provide basis for future anti-TB strategies.
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hal-01908847 , version 1 (30-10-2018)

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Charlotte Genestet, Fanny Bernard-Barret, Elisabeth Hodille, Christophe Ginevra, Florence Ader, et al.. Antituberculous drugs modulate bacterial phagolysosome avoidance and autophagy in Mycobacterium tuberculosis-infected macrophages. Tuberculosis, 2018, 111, pp.67-70. ⟨10.1016/j.tube.2018.05.014⟩. ⟨hal-01908847⟩
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