Myosin light chain kinase plays an essential role in S. flexneri dissemination

Area of Science:

• Microbiology
• Cell Biology
• Pathogen-Host Interactions

Background:

• Shigella flexneri causes bacillary dysentery and spreads between colonic epithelial cells via protrusions.
• This intercellular dissemination occurs near adherens junctions and is sensitive to junctional complex disruption.

Purpose of the Study:

• To investigate the role of myosin light chain kinase (MLCK) in the intercellular spread of Shigella flexneri.
• To determine if MLCK is involved in bacterial entry, intracellular motility, or cell-to-cell dissemination.

Main Methods:

• Treatment of infected cells with myosin light chain kinase (MLCK) inhibitors.
• Assessment of bacterial entry, intracellular multiplication, and actin-based motility.
• Evaluation of intercellular spread of S. flexneri and Listeria monocytogenes.
• Confocal microscopy to confirm the integrity of cell-cell contacts.

Main Results:

• MLCK inhibitors significantly reduced intercellular spread of S. flexneri.
• Inhibitors did not affect bacterial entry, multiplication, or actin-based motility within host cells.
• MLCK inhibitors did not inhibit the cell-to-cell spread of Listeria monocytogenes.
• Confocal microscopy confirmed that cell-cell contacts remained intact in treated cells.

Conclusions:

• MLCK plays a crucial role in the Shigella flexneri-specific mechanism of cell-to-cell dissemination.
• MLCK activity is involved in the formation of bacteria-containing protrusions and potentially their subsequent endocytosis by adjacent cells.
• The findings differentiate the spread mechanism of S. flexneri from that of Listeria monocytogenes, which is not affected by MLCK inhibition.