title: Overexpression of Differentially Expressed Genes Identified in Non-pathogenic and Pathogenic Entamoeba histolytica Clones Allow Identification of New Pathogenicity Factors Involved in Amoebic Liver Abscess Formation.
abstract: We here compared pathogenic (p) and non-pathogenic (np) isolates of Entamoeba histolytica to identify molecules involved in the ability of this parasite to induce amoebic liver abscess (ALA)-like lesions in two rodent models for the disease. We performed a comprehensive analysis of 12 clones (A1-A12) derived from a non-pathogenic isolate HM-1:IMSS-A and 12 clones (B1-B12) derived from a pathogenic isolate HM-1:IMSS-B. "Non-pathogenicity" included the induction of small and quickly resolved lesions while "pathogenicity" comprised larger abscess development that overstayed day 7 post infection. All A-clones were designated as non-pathogenic, whereas 4 out of 12 B-clones lost their ability to induce ALAs in gerbils. No correlation between ALA formation and cysteine peptidase (CP) activity, haemolytic activity, erythrophagocytosis, motility or cytopathic activity was found. To identify the molecular framework underlying different pathogenic phenotypes, three clones were selected for in-depth transcriptome analyses. Comparison of a non-pathogenic clone A1np with pathogenic clone B2p revealed 76 differentially expressed genes, whereas comparison of a non-pathogenic clone B8np with B2p revealed only 19 differentially expressed genes. Only six genes were found to be similarly regulated in the two non-pathogenic clones A1np and B8np in comparison with the pathogenic clone B2p. Based on these analyses, we chose 20 candidate genes and evaluated their roles in ALA formation using the respective gene-overexpressing transfectants. We conclude that different mechanisms lead to loss of pathogenicity. In total, we identified eight proteins, comprising a metallopeptidase, C2 domain proteins, alcohol dehydrogenases and hypothetical proteins, that affect the pathogenicity of E. histolytica.
authors: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors: Martin
authors: M
authors: Meyer
authors: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors: Helena
authors: H
authors: Fehling
authors: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors: Jenny
authors: J
authors: Matthiesen
authors: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors: Stephan
authors: S
authors: Lorenzen
authors: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors: Kathrin
authors: K
authors: Schuldt
authors: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors: Hannah
authors: H
authors: Bernin
authors: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors: Mareen
authors: M
authors: Zaruba
authors: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors: Corinna
authors: C
authors: Lender
authors: Diagnostic and Interventional Radiology Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Thomas
authors: 0000-0002-2170-9241
authors: T
authors: Ernst
authors: Diagnostic and Interventional Radiology Department and Clinic, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Harald
authors: H
authors: Ittrich
authors: Zoological Institute, Molecular Physiology, Christian-Albrechts University Kiel, Kiel, Germany.
authors: Thomas
authors: T
authors: Roeder
authors: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors: Egbert
authors: E
authors: Tannich
authors: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors: Hannelore
authors: H
authors: Lotter
authors: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors: Iris
authors: I
authors: Bruchhaus
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004748:Entamoeba histolytica / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D004749:Entamoebiasis / Q000235:genetics / Q000378:metabolism / Q000469:parasitology*; D020869:Gene Expression Profiling; D017125:Genes, Protozoan / Q000502:physiology*; D005849:Gerbillinae; D008101:Liver Abscess, Amebic / Q000469:parasitology*; D051379:Mice; D016133:Polymerase Chain Reaction; D015800:Protozoan Proteins / Q000378:metabolism; D059467:Transcriptome; D037521:Virulence Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D015800:Protozoan Proteins; D037521:Virulence Factors