Increased S-nitrosylation and proteasomal degradation of caspase-3 during infection contribute to the persistence of adherent invasive escherichia coli (AIEC) in immune cells

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)

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
Keywords:Apoptosis, escherichia coli, caspase, nitrosylation, persistence, Crohn's disease
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Walker, Professor Daniel and Roe, Professor Andrew and McIntosh, Ms Anne and Cerovic, Dr Vuk and Wall, Dr Daniel and Milling, Professor Simon and Goodyear, Professor Carl
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 > Institute of Infection Immunity and Inflammation
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
607841Survival and dissemination of enteric pathogens through exploitation and inhibition of programmed cell death pathways in circulating immune cells.Daniel WallBiotechnology and Biological Sciences Research Council (BBSRC)BB/K008005/1III - BACTERIOLOGY