Microarray analysis of <it>Shigella flexneri</it>-infected epithelial cells identifies host factors important for apoptosis inhibition

<p>Abstract</p> <p>Background</p> <p><it>Shigella flexneri </it>inhibits apoptosis in infected epithelial cells. In order to understand the pro-survival effects induced by the bacteria, we utilized apoptosis-specific microarrays to analyze the changes in euk...

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Main Authors: Ramaswamy Aishwarya V, Dubois Andre, Semino-Mora Cristina, Merrell D Scott, Faherty Christina S, Maurelli Anthony T
Format: Article
Language:English
Published: BMC 2010-04-01
Series:BMC Genomics
Online Access:http://www.biomedcentral.com/1471-2164/11/272
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author Ramaswamy Aishwarya V
Dubois Andre
Semino-Mora Cristina
Merrell D Scott
Faherty Christina S
Maurelli Anthony T
author_facet Ramaswamy Aishwarya V
Dubois Andre
Semino-Mora Cristina
Merrell D Scott
Faherty Christina S
Maurelli Anthony T
author_sort Ramaswamy Aishwarya V
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p><it>Shigella flexneri </it>inhibits apoptosis in infected epithelial cells. In order to understand the pro-survival effects induced by the bacteria, we utilized apoptosis-specific microarrays to analyze the changes in eukaryotic gene expression in both infected and uninfected cells in the presence and absence of staurosporine, a chemical inducer of the intrinsic pathway of apoptosis. The goal of this research was to identify host factors that contribute to apoptosis inhibition in infected cells.</p> <p>Results</p> <p>The microarray analysis revealed distinct expression profiles in uninfected and infected cells, and these changes were altered in the presence of staurosporine. These profiles allowed us to make comparisons between the treatment groups. Compared to uninfected cells, <it>Shigella-</it>infected epithelial cells, both in the presence and absence of staurosporine, showed significant induced expression of <it>JUN</it>, several members of the inhibitor of apoptosis gene family, nuclear factor κB and related genes, genes involving tumor protein 53 and the retinoblastoma protein, and surprisingly, genes important for the inhibition of the extrinsic pathway of apoptosis. We confirmed the microarray results for a selection of genes using <it>in situ </it>hybridization analysis.</p> <p>Conclusion</p> <p>Infection of epithelial cells with <it>S. flexneri </it>induces a pro-survival state in the cell that results in apoptosis inhibition in the presence and absence of staurosporine. The bacteria may target these host factors directly while some induced genes may represent downstream effects due to the presence of the bacteria. Our results indicate that the bacteria block apoptosis at multiple checkpoints along both pathways so that even if a cell fails to prevent apoptosis at an early step, <it>Shigella </it>will block apoptosis at the level of caspase-3. Apoptosis inhibition is most likely vital to the survival of the bacteria <it>in vivo</it>. Future characterization of these host factors is required to fully understand how <it>S. flexneri </it>inhibits apoptosis in epithelial cells.</p>
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spelling doaj.art-68bc9b27f89d4285860883797dea9cfd2022-12-22T03:25:50ZengBMCBMC Genomics1471-21642010-04-0111127210.1186/1471-2164-11-272Microarray analysis of <it>Shigella flexneri</it>-infected epithelial cells identifies host factors important for apoptosis inhibitionRamaswamy Aishwarya VDubois AndreSemino-Mora CristinaMerrell D ScottFaherty Christina SMaurelli Anthony T<p>Abstract</p> <p>Background</p> <p><it>Shigella flexneri </it>inhibits apoptosis in infected epithelial cells. In order to understand the pro-survival effects induced by the bacteria, we utilized apoptosis-specific microarrays to analyze the changes in eukaryotic gene expression in both infected and uninfected cells in the presence and absence of staurosporine, a chemical inducer of the intrinsic pathway of apoptosis. The goal of this research was to identify host factors that contribute to apoptosis inhibition in infected cells.</p> <p>Results</p> <p>The microarray analysis revealed distinct expression profiles in uninfected and infected cells, and these changes were altered in the presence of staurosporine. These profiles allowed us to make comparisons between the treatment groups. Compared to uninfected cells, <it>Shigella-</it>infected epithelial cells, both in the presence and absence of staurosporine, showed significant induced expression of <it>JUN</it>, several members of the inhibitor of apoptosis gene family, nuclear factor κB and related genes, genes involving tumor protein 53 and the retinoblastoma protein, and surprisingly, genes important for the inhibition of the extrinsic pathway of apoptosis. We confirmed the microarray results for a selection of genes using <it>in situ </it>hybridization analysis.</p> <p>Conclusion</p> <p>Infection of epithelial cells with <it>S. flexneri </it>induces a pro-survival state in the cell that results in apoptosis inhibition in the presence and absence of staurosporine. The bacteria may target these host factors directly while some induced genes may represent downstream effects due to the presence of the bacteria. Our results indicate that the bacteria block apoptosis at multiple checkpoints along both pathways so that even if a cell fails to prevent apoptosis at an early step, <it>Shigella </it>will block apoptosis at the level of caspase-3. Apoptosis inhibition is most likely vital to the survival of the bacteria <it>in vivo</it>. Future characterization of these host factors is required to fully understand how <it>S. flexneri </it>inhibits apoptosis in epithelial cells.</p>http://www.biomedcentral.com/1471-2164/11/272
spellingShingle Ramaswamy Aishwarya V
Dubois Andre
Semino-Mora Cristina
Merrell D Scott
Faherty Christina S
Maurelli Anthony T
Microarray analysis of <it>Shigella flexneri</it>-infected epithelial cells identifies host factors important for apoptosis inhibition
BMC Genomics
title Microarray analysis of <it>Shigella flexneri</it>-infected epithelial cells identifies host factors important for apoptosis inhibition
title_full Microarray analysis of <it>Shigella flexneri</it>-infected epithelial cells identifies host factors important for apoptosis inhibition
title_fullStr Microarray analysis of <it>Shigella flexneri</it>-infected epithelial cells identifies host factors important for apoptosis inhibition
title_full_unstemmed Microarray analysis of <it>Shigella flexneri</it>-infected epithelial cells identifies host factors important for apoptosis inhibition
title_short Microarray analysis of <it>Shigella flexneri</it>-infected epithelial cells identifies host factors important for apoptosis inhibition
title_sort microarray analysis of it shigella flexneri it infected epithelial cells identifies host factors important for apoptosis inhibition
url http://www.biomedcentral.com/1471-2164/11/272
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