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...

Full description

Bibliographic Details
Main Authors:	Lum, Mabel, Attridge, Stephen R., Morona, Renato
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868620/

id	pubmed-3868620
recordtype	oai_dc
spelling	pubmed-38686202013-12-23 Impact of Dynasore an Inhibitor of Dynamin II on Shigella flexneri Infection Lum, Mabel Attridge, Stephen R. Morona, Renato Research Article 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. Public Library of Science 2013-12-19 /pmc/articles/PMC3868620/ /pubmed/24367704 http://dx.doi.org/10.1371/journal.pone.0084975 Text en © 2013 Lum et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Lum, Mabel Attridge, Stephen R. Morona, Renato
spellingShingle	Lum, Mabel Attridge, Stephen R. Morona, Renato Impact of Dynasore an Inhibitor of Dynamin II on Shigella flexneri Infection
author_facet	Lum, Mabel Attridge, Stephen R. Morona, Renato
author_sort	Lum, Mabel
title	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_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_sort	impact of dynasore an inhibitor of dynamin ii on shigella flexneri infection
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.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868620/
_version_	1612040108735725568

Impact of Dynasore an Inhibitor of Dynamin II on Shigella flexneri Infection

Similar Items