title: Dynamin-related protein Drp1 and mitochondria are important for Shigella flexneri infection.
abstract: Shigella infection in epithelial cells induces cell death which is accompanied by mitochondrial dysfunction. In this study the role of the mitochondrial fission protein, Drp1 during Shigella infection in HeLa cells was examined. Significant lactate dehydrogenase (LDH) release was detected in the culture supernatant when HeLa cells were infected with Shigella at a high multiplicity of infection. Drp1 inhibition with Mdivi-1 and siRNA knockdown significantly reduced LDH release. HeLa cell death was also accompanied by mitochondrial fragmentation. Tubular mitochondrial networks were partially restored when Drp1 was depleted with either siRNA or inhibited with Mdivi-1. Surprisingly either Mdivi-1 treatment or Drp1 siRNA-depletion of HeLa cells also reduced Shigella plaque formation. The effect of Mdivi-1 on Shigella infection was assessed using the murine Sereny model, however it had no impact on ocular inflammation. Overall our results suggest that Drp1 and the mitochondria play important roles during Shigella infection.
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Mabel
authors.initials: M
authors.lastname: Lum
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia. Electronic address: renato.morona@adelaide.edu.au.
authors.forename: Renato
authors.initials: R
authors.lastname: Morona
mesh_terms: D000818:Animals; D016923:Cell Death; D004195:Disease Models, Animal; D034281:Dynamins / Q000378:metabolism*; D004405:Dysentery, Bacillary / Q000382:microbiology / Q000473:pathology; D004847:Epithelial Cells / Q000382:microbiology* / Q000502:physiology; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000382:microbiology* / Q000502:physiology; D012763:Shigella flexneri / Q000502:physiology*
chemical_list: D007770:L-Lactate Dehydrogenase; C486391:Dnm1l protein, mouse; D034281:Dynamins
keywords: Cell death; Cell-to-cell spreading; Drp1; Mdivi-1; Mitochondria; Shigella flexneri