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Comparative proteomic analysis of two Entamoeba histolytica strains with different virulence phenotypes identifies peroxiredoxin as an important component of amoebic virulence
Author(s) -
Davis Paul H.,
Zhang Xiaochun,
Guo Jianhua,
Townsend R. Reid,
Stanley Samuel L.
Publication year - 2006
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2006.05344.x
Subject(s) - entamoeba histolytica , virulence , biology , microbiology and biotechnology , peroxiredoxin , phenotype , gene , genetics , enzyme , peroxidase , biochemistry
Summary Entamoeba histolytica is a protozoan intestinal parasite that causes amoebic colitis and amoebic liver abscess. To identify virulence factors of E. histolytica , we first defined the phenotypes of two E. histolytica strains, HM‐1:IMSS, the prototype virulent strain, and E. histolytica Rahman, a strain that was reportedly less virulent than HM‐1:IMSS. We found that compared with HM‐1:IMSS, Rahman has a defect in erythrophagocytosis and the ability to cause amoebic colitis in human colonic xenografts. We used differential in‐gel 2D electrophoresis to compare the proteome of Rahman and HM‐1:IMSS, and identified six proteins that were differentially expressed above a fivefold level between the two organisms. These included two proteins with antioxidative properties (peroxiredoxin and superoxide dismutase), and three proteins of unknown function, grainin 1, grainin 2 and a protein containing a LIM‐domain. Overexpression of peroxiredoxin in Rahman rendered the transgenic trophozoites more resistant to killing by H 2 O 2 in vitro , and infection with Rahman trophozoites expressing higher levels of peroxiredoxin was associated with higher levels of intestinal inflammation in human colonic xenografts, and more severe disease based on histology. In contrast, higher levels of grainin appear to be associated with a reduced virulence phenotype, and E. histolytica HM‐1:IMSS trophozoites infecting human intestinal xenografts show marked decreases in grainin expression. Our data indicate that there are definable molecular differences between Rahman and HM‐1:IMSS that may explain the phenotypic differences, and identify peroxiredoxin as an important component of virulence in amoebic colitis.