Dunne, K.A. et al. (2013) Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells. PLoS ONE, 8(7), e68386. (doi: 10.1371/journal.pone.0068386) (PMID:23861899) (PMCID:PMC3701656)
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Abstract
Adherent invasive Escherichia coli (AIEC) have been implicated as a causative agent of Crohn's disease (CD) due to their isolation from the intestines of CD sufferers and their ability to persist in macrophages inducing granulomas. The rapid intracellular multiplication of AIEC sets it apart from other enteric pathogens such as Salmonella Typhimurium which after limited replication induce programmed cell death (PCD). Understanding the response of infected cells to the increased AIEC bacterial load and associated metabolic stress may offer insights into AIEC pathogenesis and its association with CD. Here we show that AIEC persistence within macrophages and dendritic cells is facilitated by increased proteasomal degradation of caspase-3. In addition S-nitrosylation of pro- and active forms of caspase-3, which can inhibit the enzymes activity, is increased in AIEC infected macrophages. This S-nitrosylated caspase-3 was seen to accumulate upon inhibition of the proteasome indicating an additional role for S-nitrosylation in inducing caspase-3 degradation in a manner independent of ubiquitination. In addition to the autophagic genetic defects that are linked to CD, this delay in apoptosis mediated in AIEC infected cells through increased degradation of caspase-3, may be an essential factor in its prolonged persistence in CD patients.
| Item Type: | Articles |
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| Keywords: | Apoptosis, escherichia coli, caspase, nitrosylation, persistence, Crohn's disease |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | McIntosh, Ms Anne and Wall, Dr Daniel and Milling, Professor Simon and Walker, Professor Daniel and Roe, Professor Andrew and Goodyear, Professor Carl and Cerovic, Dr Vuk |
| Authors: | Dunne, K.A., Allam, A., McIntosh, A., Houston, S.A., Cerovic, V., Goodyear, C.S., Roe, A.J., Beatson, S.A., Milling, S.W., Walker, D., and Wall, D.M. |
| Subjects: | Q Science > QR Microbiology > QR180 Immunology |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Research Group: | Wall |
| Journal Name: | PLoS ONE |
| Publisher: | Public Library of Science |
| ISSN: | 1932-6203 |
| Copyright Holders: | Copyright © 2013 The Authors |
| First Published: | First published in PLoS ONE 8(7):e68386 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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