Salmonella pathogenesis and processing of secreted effectors by caspase-3.
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.
Department of Pediatric Gastroenterology and Nutrition, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02129, USA.|Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
C V
CV
Srikanth
Department of Pediatric Gastroenterology and Nutrition, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02129, USA.|Institute of Infection, Immunity & Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, G12 8QQ, UK.
Daniel M
DM
Wall
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Ana
A
Maldonado-Contreras
Department of Pediatric Gastroenterology and Nutrition, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02129, USA.
Haining
H
Shi
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907.
Daoguo
D
Zhou
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Zachary
Z
Demma
Department of Pediatric Gastroenterology and Nutrition, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02129, USA.|Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Karen L
KL
Mumy
Department of Pediatric Gastroenterology and Nutrition, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02129, USA.|Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Beth A
BA
McCormick
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005759:Gastroenteritis / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000382:microbiology*; D007422:Intestines / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D020556:Neutrophil Infiltration; D012481:Salmonella Infections, Animal / Q000382:microbiology* / Q000473:pathology; D012486:Salmonella typhimurium / Q000378:metabolism* / Q000472:pathogenicity*; D037521:Virulence Factors / Q000378:metabolism
D001426:Bacterial Proteins; D008840:Microfilament Proteins; D050505:Mutant Proteins; C118287:SipA protein, Salmonella; D037521:Virulence Factors; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3