Figure 1.

VacA mechanism of action. H. pylori secretes VacA toxin that, upon insertion and oligomerization in the plasma membrane, impairs the activity of the lysosomal calcium channel MCOLN1. Blocking MCOLN1 disrupts vesicular retrograde trafficking affecting the delivery of CTSD to lysosomes, leading to non-degradative lysosomes. These dysfunctional lysosomes are unable to degrade (1) the bacteria taken up by the endosomal pathway or (2) the intracellular bacteria that trigger autophagy. Dysfunctional endolysosomes and autophagosomes serve as an intracellular niche that confers H. pylori survival.