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 prote cted by a variant surface glycoprotein that is anchored in the plasma membrane through covalent attachment of the COOH terminus to a glycosy lphosphatidylinositol. 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 th e surface VSG can be observed within a few minutes on lysis of trypano somes in vitro. To investigate whether the ability to cleave the membr ane 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 throug h an entire life cycle and maintain a persistent infection in mice. Th us the GPI-PLC is not an essential activity and is not necessary for a ntigenic variation. However, mice infected with the mutant trypanosome s have a reduced parasitemia and survive longer than those infected wi th control trypanosomes. This phenotype is partially alleviated when t he null mutant is modified to express low levels of GPI-PLC.