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Science 330 (6002): 390-393

Copyright © 2010 by the American Association for the Advancement of Science

Salmonella Pathogenesis and Processing of Secreted Effectors by Caspase-3

C. V. Srikanth,1,2,* Daniel M. Wall,1,3,* Ana Maldonado-Contreras,2 Hai Ning Shi,1 Daoguo Zhou,4 Zachary Demma,2 Karen L. Mumy,1,2 Beth A. McCormick1,2,{dagger}

Abstract: The enteric pathogen Salmonella enterica serovar Typhimurium causes food poisoning resulting in gastroenteritis. The S. Typhimurium effector Salmonella invasion protein A (SipA) promotes gastroenteritis by functional motifs that trigger either mechanisms of inflammation or bacterial entry. During infection of intestinal epithelial cells, SipA was found to be responsible for the early activation of caspase-3, an enzyme that is required for SipA cleavage at a specific recognition motif that divided the protein into its two functional domains and activated SipA in a manner necessary for pathogenicity. Other caspase-3 cleavage sites identified in S. Typhimurium appeared to be restricted to secreted effector proteins, which indicates that this may be a general strategy used by this pathogen for processing of its secreted effectors.

1 Department of Pediatric Gastroenterology and Nutrition, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02129, USA.
2 Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
3 Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
4 Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: Beth.McCormick{at}

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