UMMS Affiliation
Department of Microbiology and Physiological Systems
Publication Date
2017-09-01
Document Type
Article
Disciplines
Bacterial Infections and Mycoses | Immunology and Infectious Disease | Microbiology
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, which can pass through the type three secretion system, allowed visualization 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 visualization 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.
Keywords
Salmonella, SipA, caspase-3, caspases, host-pathogen interactions, imaging, immune cells, microscopy
Rights and Permissions
Copyright © 2017 McIntosh et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
DOI of Published Version
10.1128/IAI.00393-17
Source
Infect Immun. 2017 Sep; 85(9): e00393-17. Published online 2017 Aug 18. Prepublished online 2017 Jun 19. doii:10.1128/IAI.00393-17. Link to article on publisher's site
Journal/Book/Conference Title
Infection and immunity
Related Resources
PubMed ID
28630067
Repository Citation
McIntosh, Anne; Meikle, Lynsey M.; Ormsby, Michael J.; McCormick, Beth A.; Christie, John M.; Brewer, James M.; Roberts, Mark; and Wall, Daniel M., "SipA Activation of Caspase-3 Is a Decisive Mediator of Host Cell Survival at Early Stages of Salmonella enterica Serovar Typhimurium Infection" (2017). Open Access Articles. 3229.
https://escholarship.umassmed.edu/oapubs/3229
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Bacterial Infections and Mycoses Commons, Immunology and Infectious Disease Commons, Microbiology Commons