Yersinia entry into host cells requires Rab5-dependent dephosphorylation of PI(4,5)P₂ and membrane scission

Area of Science:

• Cell biology
• Microbiology
• Molecular biology

Background:

• Bacteria like Yersinia pseudotuberculosis invade host cells using mechanisms resembling phagocytosis.
• Understanding the precise molecular events during bacterial entry into host cells is crucial for developing therapeutic strategies.

Purpose of the Study:

• To elucidate the molecular mechanisms governing invasion vacuole formation by Yersinia pseudotuberculosis.
• To identify host factors and signaling pathways involved in the scission of prevacuoles during bacterial invasion.

Main Methods:

• Analysis of Yersinia pseudotuberculosis interaction with host cells.
• Microscopy and biochemical assays to track membrane dynamics and protein recruitment.
• Investigating the roles of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂), inositol phosphatases (OCRL, Inpp5b), Rab5 GTPase, and phosphatidylinositol 3-kinase (PI3K).

Main Results:

• Yersinia engages host cell integrins, residing in PI(4,5)P₂-rich prevacuoles connected to the plasma membrane.
• Prevacuole scission into sealed compartments requires PI(4,5)P₂ hydrolysis, coinciding with OCRL and Inpp5b recruitment.
• Rab5 association with prevacuoles is essential for OCRL/Inpp5b recruitment and PI(4,5)P₂ hydrolysis.
• PI3K activity is necessary for Rab5-positive vesicle fusion and prevacuole scission.

Conclusions:

• Yersinia invasion is a multistep process involving the formation of a protective prevacuole.
• Host cell factors, including Rab5, OCRL, and Inpp5b, are recruited to mediate membrane fission and facilitate bacterial entry.
• The study reveals a novel mechanism of host cell invasion orchestrated by bacterial pathogens.