McIntosh, A., Meikle, L. M., Ormsby, M. J., McCormick, B. A., Christie, J. M. , Brewer, J. M. , Roberts, M. and Wall, D. M. (2017) SipA activation of caspase-3 is a decisive mediator of host cell survival at early stages of Salmonella enterica serovar typhimurium Infection. Infection and Immunity, 85(9), e00393-17. (doi: 10.1128/IAI.00393-17) (PMID:28630067) (PMCID:PMC5563584)
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Abstract
Salmonella invasion protein A (SipA) is a dual function effector protein that plays roles in both actin polymerization and caspase-3 activation in intestinal epithelial cells. To date its function in other cell types has remained largely unknown despite its expression in multiple cell types and its extracellular secretion during infection. Here we show that in macrophages SipA induces increased caspase-3 activation early in infection. This activation required a threshold level of SipA linked to multiplicity of infection and may be a limiting factor controlling bacterial numbers in infected macrophages. In polymorphonuclear leukocytes SipA, or other Salmonella Pathogenicity Island 1 effectors, had no effect on induction of caspase-3 activation either alone or in the presence of whole bacteria. Tagging of SipA with the small fluorescent phiLOV tag that can pass through the Type Three Secretion System allowed visualisation and quantification of caspase-3 activation by SipA-phiLOV in macrophages. Additionally, SipA-phiLOV activation of caspase-3 could be tracked in the intestine through multiphoton laser scanning microscopy in an ex vivo intestinal model. This allowed visualisation of areas where the intestinal epithelium had been compromised and demonstrated the potential use of this fluorescent tag for in vivo tracking of individual effectors.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Roberts, Professor Mark and McIntosh, Ms Anne and Brewer, Professor James and Ormsby, Dr Michael and Meikle, Dr Lynsey and Wall, Dr Daniel and Christie, Professor John |
| Authors: | McIntosh, A., Meikle, L. M., Ormsby, M. J., McCormick, B. A., Christie, J. M., Brewer, J. M., Roberts, M., and Wall, D. M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
| Journal Name: | Infection and Immunity |
| Publisher: | American Society for Microbiology |
| ISSN: | 0019-9567 |
| ISSN (Online): | 1098-5522 |
| Published Online: | 19 June 2017 |
| Copyright Holders: | Copyright © 2017 The Authors |
| First Published: | First published in Infection and Immunity 85(9):e00393-17 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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