Dynamin-related protein Drp1 and mitochondria are important for Shigella flexneri infection

Area of Science:

• Microbiology
• Cell Biology
• Mitochondrial Biology

Background:

• Shigella infection triggers epithelial cell death and mitochondrial dysfunction.
• The mitochondrial fission protein Drp1 (dynamin-related protein 1) is implicated in cellular processes.
• Understanding Drp1's role in Shigella pathogenesis is crucial for host-pathogen interaction studies.

Purpose of the Study:

• To investigate the role of the mitochondrial fission protein Drp1 during Shigella infection in HeLa cells.
• To determine if modulating Drp1 activity affects Shigella-induced cell death and bacterial dissemination.

Main Methods:

• HeLa cells were infected with Shigella at a high multiplicity of infection.
• Cell death was assessed by measuring lactate dehydrogenase (LDH) release.
• Drp1 function was inhibited using Mdivi-1 and siRNA knockdown.
• Mitochondrial morphology was analyzed.
• Shigella plaque formation was quantified.
• The effect of Mdivi-1 was tested in the murine Sereny model.

Main Results:

• Significant LDH release, indicating cell death, was observed during Shigella infection.
• Inhibition or depletion of Drp1 significantly reduced LDH release.
• Shigella infection caused mitochondrial fragmentation, which was partially restored by Drp1 inhibition/depletion.
• Drp1 inhibition/depletion also reduced Shigella plaque formation in vitro.
• Mdivi-1 treatment did not impact ocular inflammation in the murine Sereny model.

Conclusions:

• Drp1 plays a significant role in Shigella-induced epithelial cell death.
• Mitochondrial dynamics, regulated by Drp1, are important during Shigella infection.
• Targeting Drp1 may offer a strategy to limit Shigella dissemination, although in vivo efficacy requires further investigation.