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

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...

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Main Authors: Mabel Lum, Stephen R Attridge, Renato Morona
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3868620?pdf=render
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author Mabel Lum
Stephen R Attridge
Renato Morona
author_facet Mabel Lum
Stephen R Attridge
Renato Morona
author_sort Mabel Lum
collection DOAJ
description 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.
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spelling doaj.art-f7024dc1667c4b5e94ab711161a8b8962022-12-21T19:58:04ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8497510.1371/journal.pone.0084975Impact of dynasore an inhibitor of dynamin II on Shigella flexneri infection.Mabel LumStephen R AttridgeRenato MoronaShigella 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.http://europepmc.org/articles/PMC3868620?pdf=render
spellingShingle Mabel Lum
Stephen R Attridge
Renato Morona
Impact of dynasore an inhibitor of dynamin II on Shigella flexneri infection.
PLoS ONE
title Impact of dynasore an inhibitor of dynamin II on Shigella flexneri infection.
title_full Impact of dynasore an inhibitor of dynamin II on Shigella flexneri infection.
title_fullStr Impact of dynasore an inhibitor of dynamin II on Shigella flexneri infection.
title_full_unstemmed Impact of dynasore an inhibitor of dynamin II on Shigella flexneri infection.
title_short Impact of dynasore an inhibitor of dynamin II on Shigella flexneri infection.
title_sort impact of dynasore an inhibitor of dynamin ii on shigella flexneri infection
url http://europepmc.org/articles/PMC3868620?pdf=render
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AT renatomorona impactofdynasoreaninhibitorofdynaminiionshigellaflexneriinfection