Diarrhea and colitis in mice require the Salmonella pathogenicity island 2-encoded secretion function but not SifA or Spv effectors.
We investigated the roles of Salmonella pathogenicity island 2 (SPI-2) and two SPI-2 effectors in Salmonella colitis and diarrhea in genetically resistant BALB/c.D2(Slc11a1) congenic mice with the wild-type Nramp1 locus. Wild-type Salmonella enterica serovar Typhimurium 14028s caused a pan-colitis, and the infected mice developed frank diarrhea with a doubling of the fecal water content. An ssaV mutant caused only a 26% increase in fecal water content, without producing the pathological changes of colitis, and it did not cause weight loss over a 1-week period of observation. However, two SPI-2 effector mutants, the spvB and sifA mutants, and a double spvB sifA mutant caused diarrhea and colitis, even though the sifA mutant was sensitive to killing by bone marrow-derived macrophages from BALB/c.D2 mice and was severely impaired in extraintestinal growth but not in growth in the cecum. These results demonstrate that systemic S. enterica infection and diarrhea/colitis are distinct pathogenic processes and that only the former requires spvB and sifA.
Department of Medicine, Division of Infectious Diseases, UC San Diego School of Medicine, San Diego, California, USA. jfierer@ucsd.edu
Joshua
J
Fierer
Sharon
S
Okamoto
Ananya
A
Banerjee
Donald G
DG
Guiney
D036002:ADP Ribose Transferases / Q000235:genetics / Q000378:metabolism; D000483:Alleles; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D003092:Colitis / Q000382:microbiology*; D003106:Colon / Q000473:pathology; D003967:Diarrhea / Q000382:microbiology*; D005243:Feces / Q000737:chemistry; D005260:Female; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D012475:Salmonella / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity; D012481:Salmonella Infections, Animal / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D013047:Specific Pathogen-Free Organisms; D014774:Virulence / Q000235:genetics; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism; D000099173:Natural Resistance-associated Macrophage Protein 1
D036002:ADP Ribose Transferases; D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; D037521:Virulence Factors; D000099173:Natural Resistance-associated Macrophage Protein 1; C440638:SPI-2 protein, Salmonella; C421862:SifA protein, Salmonella; C415223:spvB protein, Salmonella enterica virulence plasmid