Cellular machinery to fuse antimicrobial autophagosome with lysosome

Abstract

Autophagy is an intracellular bulk degradation/recycling system that turns over cellular constituents and also functions to degrade intracellular foreign microbial invaders by a process termed xenophagy (antimicrobial autophagy). We previously showed that intracellular group A Streptococcus (GAS) organisms are captured by xenophagosomes, then degraded following fusion with lysosomes. Very recently, we analyzed the molecular mechanism underlying xenophagosome/lysosome fusion and found that endocytic soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) were involved. Knockdown of the combinational SNARE proteins Vti1b and VAMP8 with siRNAs disturbed autophagic fusion with lysosomes, and cellular bactericidal efficiency was significantly diminished. Furthermore, knockdown of those SNAREs inhibited the fusion of canonical autophagosomes with lysosomes. In addition, important findings showed that Vti1b is derived from autophagic compartments, whereas VAMP8 originates from lysosomes. Together, these results strongly suggest that SNARE proteins Vti1b and VAMP8 mediate the fusion of antimicrobial and canonical autophagosomes with lysosomes, an essential event for autophagic degradation.