title: Impact of dynasore an inhibitor of dynamin II on Shigella flexneri infection.
abstract: Shigella flexneri remains a significant human pathogen due to high morbidity among children < 5 years in developing countries. One of the key features of Shigella infection is the ability of the bacterium to initiate actin tail polymerisation to disseminate into neighbouring cells. Dynamin II is associated with the old pole of the bacteria that is associated with F-actin tail formation. Dynamin II inhibition with dynasore as well as siRNA knockdown significantly reduced Shigella cell to cell spreading in vitro. The ocular mouse Sereny model was used to determine if dynasore could delay the progression of Shigella infection in vivo. While dynasore did not reduce ocular inflammation, it did provide significant protection against weight loss. Therefore dynasore's effects in vivo are unlikely to be related to the inhibition of cell spreading observed in vitro. We found that dynasore decreased S. flexneri-induced HeLa cell death in vitro which may explain the protective effect observed in vivo. These results suggest the administration of dynasore or a similar compound during Shigella infection could be a potential intervention strategy to alleviate disease symptoms.
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.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Attridge
authors.affiliation: School of Molecular and Biomedical Science, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Renato
authors.initials: R
authors.lastname: Morona
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects; D003224:Congo Red; D034285:Dynamin II / Q000037:antagonists & inhibitors*; D004405:Dysentery, Bacillary / Q000188:drug therapy*; D048168:Escherichia coli K12; D005123:Eye / Q000382:microbiology; D006367:HeLa Cells; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology* / Q000627:therapeutic use; D008164:Luminescent Proteins; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D000097573:Red Fluorescent Protein
chemical_list: D003224:Congo Red; D034285:Dynamin II; D006835:Hydrazones; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide