A coat protein on phagosomes involved in the intracellular survival of mycobacteria

Area of Science:

• Microbiology
• Cell Biology
• Immunology

Background:

• Mycobacteria are intracellular pathogens that evade host defenses within macrophage phagosomes through poorly understood mechanisms.
• Phagosome maturation, involving fusion with lysosomes for degradation, is a key host defense strategy.
• The mechanisms by which mycobacteria interfere with phagosome maturation are largely unknown.

Purpose of the Study:

• To identify host factors involved in mycobacterial survival within macrophages.
• To elucidate the mechanism by which mycobacteria evade lysosomal degradation.
• To investigate the role of host protein TACO in mycobacterial intracellular survival.

Main Methods:

• Identification and characterization of a host WD repeat protein (TACO) recruited to phagosomes.
• Analysis of TACO recruitment and retention by live versus dead mycobacteria.
• Assessment of mycobacterial fate in macrophages with and without TACO expression.
• Investigation of TACO's effect on lysosomal delivery in non-macrophage cells.

Main Results:

• A host WD repeat protein, TACO, is actively recruited and retained on phagosomes by living mycobacteria.
• TACO is a component of the phagosome coat normally released before lysosome fusion.
• Macrophages lacking TACO efficiently deliver mycobacteria to lysosomes for degradation.
• TACO expression in non-macrophages inhibits lysosomal delivery and prolongs mycobacterial survival.

Conclusions:

• Active retention of TACO on phagosomes by live mycobacteria is a novel mechanism to evade host immunity.
• This retention prevents phagosome-lysosome fusion, thereby allowing mycobacteria to survive intracellularly.
• Targeting TACO or its interaction with mycobacteria could represent a therapeutic strategy against mycobacterial infections.