title: The GPI-phospholipase C of Trypanosoma brucei is nonessential but influences parasitemia in mice.
abstract: In the mammalian host, the cell surface of Trypanosoma brucei is protected by a variant surface glycoprotein that is anchored in the plasma membrane through covalent attachment of the COOH terminus to a glycosylphosphatidylinositol. The trypanosome also contains a phospholipase C (GPI-PLC) that cleaves this anchor and could thus potentially enable the trypanosome to shed the surface coat of VSG. Indeed, release of the surface VSG can be observed within a few minutes on lysis of trypanosomes in vitro. To investigate whether the ability to cleave the membrane anchor of the VSG is an essential function of the enzyme in vivo, a GPI-PLC null mutant trypanosome has been generated by targeted gene deletion. The mutant trypanosomes are fully viable; they can go through an entire life cycle and maintain a persistent infection in mice. Thus the GPI-PLC is not an essential activity and is not necessary for antigenic variation. However, mice infected with the mutant trypanosomes have a reduced parasitemia and survive longer than those infected with control trypanosomes. This phenotype is partially alleviated when the null mutant is modified to express low levels of GPI-PLC.
authors.affiliation: Department of Biochemistry, Cambridge University, United Kingdom.
authors.forename: H
authors.initials: H
authors.lastname: Webb
authors.forename: N
authors.initials: N
authors.lastname: Carnall
authors.forename: L
authors.initials: L
authors.lastname: Vanhamme
authors.forename: S
authors.initials: S
authors.lastname: Rolin
authors.forename: J
authors.initials: J
authors.lastname: Van Den Abbeele
authors.forename: S
authors.initials: S
authors.lastname: Welburn
authors.forename: E
authors.initials: E
authors.lastname: Pays
authors.forename: M
authors.initials: M
authors.lastname: Carrington
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D017261:Glycosylphosphatidylinositols / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D016254:Mutagenesis, Insertional; D018512:Parasitemia / Q000201:enzymology* / Q000235:genetics / Q000469:parasitology; D010641:Phenotype; D017384:Sequence Deletion; D014346:Trypanosoma brucei brucei / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D014353:Trypanosomiasis, African / Q000201:enzymology* / Q000235:genetics / Q000469:parasitology; D010738:Type C Phospholipases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D017261:Glycosylphosphatidylinositols; D010738:Type C Phospholipases