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The GPI-phospholipase C of Trypanosoma brucei is nonessential but influences parasitemia in mice.

Webb H, Carnall N, Vanhamme L, Rolin S, Van Den Abbeele J, Welburn S, Pays E, Carrington M - J. Cell Biol. (1997)

Bottom Line: 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 mutant trypanosome has been generated by targeted gene deletion.Thus the GPI-PLC is not an essential activity and is not necessary for antigenic variation.This phenotype is partially alleviated when the mutant is modified to express low levels of GPI-PLC.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Cambridge University, United Kingdom.

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 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 mutant is modified to express low levels of GPI-PLC.

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The course of infection with PLC− trypanosomes in six  individual mice. Parasite densities are expressed as log10 number  of trypanosomes/ml of blood.
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Figure 6: The course of infection with PLC− trypanosomes in six individual mice. Parasite densities are expressed as log10 number of trypanosomes/ml of blood.

Mentions: The initial stabilates of the bloodstream form of PLC− trypanosomes were produced in immunosuppressed mice and so had not interacted with the host immune system. To establish a persistent infection in an immunologically competent mouse, trypanosomes have to exchange the metacyclic VSG for a bloodstream form VSG, and this occurs in the majority of the population (Esser and Schoenbechler, 1985). Subsequently a small subset of the population undergoes antigenic variation to avoid antibody-mediated lysis. To test whether the VSG-shedding properties of GPI-PLC play an essential part in these two processes, infections were established in laboratory mice. Persistent infections lasting >50 d were readily observed with the PLC− bloodstream-form population. Parasitemic profiles for six individual mice for the first 50 d after infection are given in Fig. 6. Each mouse shows the same basic pattern that is in turn broadly similar to the profiles observed previously for six cloned T. brucei stocks (Turner et al., 1995). An initial peak of parasitemia is followed by a relapse and recrudescence (‘trough') to a comparatively level plateau, punctuated by one or more further troughs.


The GPI-phospholipase C of Trypanosoma brucei is nonessential but influences parasitemia in mice.

Webb H, Carnall N, Vanhamme L, Rolin S, Van Den Abbeele J, Welburn S, Pays E, Carrington M - J. Cell Biol. (1997)

The course of infection with PLC− trypanosomes in six  individual mice. Parasite densities are expressed as log10 number  of trypanosomes/ml of blood.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139819&req=5

Figure 6: The course of infection with PLC− trypanosomes in six individual mice. Parasite densities are expressed as log10 number of trypanosomes/ml of blood.
Mentions: The initial stabilates of the bloodstream form of PLC− trypanosomes were produced in immunosuppressed mice and so had not interacted with the host immune system. To establish a persistent infection in an immunologically competent mouse, trypanosomes have to exchange the metacyclic VSG for a bloodstream form VSG, and this occurs in the majority of the population (Esser and Schoenbechler, 1985). Subsequently a small subset of the population undergoes antigenic variation to avoid antibody-mediated lysis. To test whether the VSG-shedding properties of GPI-PLC play an essential part in these two processes, infections were established in laboratory mice. Persistent infections lasting >50 d were readily observed with the PLC− bloodstream-form population. Parasitemic profiles for six individual mice for the first 50 d after infection are given in Fig. 6. Each mouse shows the same basic pattern that is in turn broadly similar to the profiles observed previously for six cloned T. brucei stocks (Turner et al., 1995). An initial peak of parasitemia is followed by a relapse and recrudescence (‘trough') to a comparatively level plateau, punctuated by one or more further troughs.

Bottom Line: 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 mutant trypanosome has been generated by targeted gene deletion.Thus the GPI-PLC is not an essential activity and is not necessary for antigenic variation.This phenotype is partially alleviated when the mutant is modified to express low levels of GPI-PLC.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry, Cambridge University, United Kingdom.

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 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 mutant is modified to express low levels of GPI-PLC.

Show MeSH
Related in: MedlinePlus