Listeria InlB Expedites Vacuole Escape and Intracellular Proliferation by Promoting Rab7 Recruitment via Vps34.

Area of Science:

• Microbiology
• Cell Biology
• Pathogenesis

Background:

• Listeria monocytogenes requires rapid phagosomal escape for intracellular replication.
• Phagosomal escape occurs from early endosomes (Rab5-negative) to late endosomes (Rab7-positive).

Purpose of the Study:

• To investigate the role of the invasin InlB in Listeria monocytogenes intracellular pathogenesis.
• To elucidate the mechanisms by which InlB influences phagosomal maturation and escape.

Main Methods:

• Mutant analysis of L. monocytogenes.
• HeLa cell experiments to track LCV maturation.
• Small interfering RNA (siRNA) knockdown of Vps34.
• Analysis of Rab GTPase recruitment (Rab5, Rab7) and PI3K/PI3P signaling.

Main Results:

• InlB is essential for optimal intracellular proliferation of L. monocytogenes.
• InlB promotes early phagosomal escape and Rab7 acquisition by the LCV.
• InlB-dependent recruitment of class III PI3K Vps34 and PI3P accumulation were observed.
• Vps34 is required for Rab7 recruitment, early escape, and InlB-dependent proliferation.

Conclusions:

• InlB accelerates LCV maturation into an escape-favorable late phagosome by subverting class III PI3K/Vps34 signaling.
• InlB acts as a virulence factor promoting intracellular proliferation.
• L. monocytogenes, a cytosolic pathogen, manipulates endocytic trafficking for survival, distinct from vacuolar pathogens.
• InlB exhibits dual roles: inducing phagocytosis via class I PI3K and promoting intracellular survival via class III PI3K.