Impact of dynasore an inhibitor of dynamin II on Shigella flexneri infection

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dc.contributor.authorLum, M.
dc.contributor.authorAttridge, S.
dc.contributor.authorMorona, R.
dc.contributor.editorMantis, N.J.
dc.date.issued2013
dc.description.abstractShigella 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.
dc.description.statementofresponsibilityMabel Lum, Stephen R. Attridge and Renato Morona
dc.identifier.citationPLoS One, 2013; 8(12):e84975-1-e84975-17
dc.identifier.doi10.1371/journal.pone.0084975
dc.identifier.issn1932-6203
dc.identifier.issn1932-6203
dc.identifier.orcidMorona, R. [0000-0001-7009-7440]
dc.identifier.urihttp://hdl.handle.net/2440/82975
dc.language.isoen
dc.publisherPublic Library of Science
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/565526
dc.rights© 2013 Lum et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.source.urihttps://doi.org/10.1371/journal.pone.0084975
dc.subjectEye
dc.subjectHela Cells
dc.subjectAnimals
dc.subjectMice, Inbred BALB C
dc.subjectHumans
dc.subjectMice
dc.subjectEscherichia coli K12
dc.subjectDysentery, Bacillary
dc.subjectHydrazones
dc.subjectCongo Red
dc.subjectDynamin II
dc.subjectLuminescent Proteins
dc.subjectMicroscopy, Fluorescence
dc.subjectBlotting, Western
dc.subjectAnalysis of Variance
dc.subjectCell Death
dc.subjectMale
dc.subjectRed Fluorescent Protein
dc.titleImpact of dynasore an inhibitor of dynamin II on Shigella flexneri infection
dc.typeJournal article
pubs.publication-statusPublished

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