The GPI-phospholipase C of Trypanosoma brucei is nonessential but influences parasitemia in mice.
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.
Webb
H
H
Department of Biochemistry, Cambridge University, United Kingdom.
Carnall
N
N
Vanhamme
L
L
Rolin
S
S
Van Den Abbeele
J
J
Welburn
S
S
Pays
E
E
Carrington
M
M
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*
D017261:Glycosylphosphatidylinositols; D010738:Type C Phospholipases