Listeria monocytogenes exploits normal host cell processes to spread from cell to cell

Area of Science:

• Microbiology
• Cell Biology
• Infectious Diseases

Background:

• Listeria monocytogenes is a bacterial pathogen that invades host cells.
• Intercellular spread is a key virulence factor for L. monocytogenes, facilitated by actin-based motility.
• The bacterial protein ActA is crucial for mediating actin-based motility and cell-to-cell spread.

Purpose of the Study:

• To investigate the factors influencing intercellular spread of Listeria monocytogenes.
• To characterize the dynamics of membrane-bound protrusions during bacterial spread.
• To explore the potential role of host cell endocytosis in bacterial intercellular transmission.

Main Methods:

• Infection of MDCK cell monolayers expressing GFP-actin with L. monocytogenes.
• Live-cell video microscopy to observe bacterial spread and actin dynamics.
• Analysis of membrane-bound protrusions and their interaction with host cells.

Main Results:

• Intercellular spread probability decreased with host cell monolayer age and cell-cell contacts.
• Bacterium-dependent movement of protrusions was observed, followed by vacuole formation and lysis.
• Actin filaments in protrusions showed reduced turnover rates compared to cytoplasmic actin tails.
• Recovery of bacterial motility in recipient cells was delayed (1-2 generations), potentially due to ActA cleavage by Mpl.
• Host cell surface fragments were endocytosed in the absence of bacteria, suggesting paracytophagy.

Conclusions:

• Host cell confluency and age negatively regulate Listeria monocytogenes intercellular spread.
• Bacterial spread involves dynamic protrusions that collapse into vacuoles, leading to lysis.
• Listeria monocytogenes may hijack host cell endocytic pathways, specifically paracytophagy, for efficient intercellular transmission.