The Trypanosoma brucei reference strain TREU927/4 contains T. brucei rhodesiense-specific SRA sequences, but displays a distinct phenotype of relative resistance to human serum.
The Trypanosoma brucei reference strain TREU927/4 exhibits some resistance to lysis by normal human serum (NHS), but this resistance is never complete even after selection. The genome of this strain contains a minimum of eight sequences related to the T. brucei rhodesiense-specific serum resistance-associated gene (SRA), which encodes a truncated variant surface glycoprotein (VSG) conferring full resistance to lysis by NHS. We selected two sequences showing the highest similarity to SRA and also preceded by a region ("cotransposed region") present immediately upstream from SRA in the VSG expression site termed R-ES, where SRA is expressed in T. brucei rhodesiense. Whereas one of these sequences appears to be a pseudogene, the other, which is contained within a cluster of VSG basic copies (BCs), encodes a VSG truncated in the C-terminal domain. In the latter gene, an inserted region encoding surface-exposed loops similar to those of the BoTat 1.20 VSG interrupts the full SRA sequence. Therefore, this gene was termed SRA-BC, for the putative VSG basic copy from which SRA was derived. Neither this gene nor other SRA-like sequences appeared to be responsible for the relative resistance of TREU927/4 to NHS, since (i) transfection of SRA-BC in T. brucei brucei did not confer increased resistance; (ii) SRA transcripts could not be detected in this strain, even when focusing the search on the limited SRA sequence necessary to confer resistance and when using strain-specific SRA probes on RNA from cells selected in the presence of NHS.
Laboratory of Molecular Parasitology, Department of Molecular Biology, IBMM, Free University of Brussels, 12, rue des Professeurs Jeener et Brachet, B-6041 Gosselies, Belgium.
Luc
L
Vanhamme
Hubert
H
Renauld
Laurence
L
Lecordier
Philippe
P
Poelvoorde
Jan
J
Van Den Abbeele
Etienne
E
Pays
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D017124:Conserved Sequence; D023061:Gene Order; D017125:Genes, Protozoan; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D005810:Multigene Family; D010641:Phenotype; D021382:Protein Sorting Signals; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D044967:Serum; D014346:Trypanosoma brucei brucei / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D016833:Trypanosoma brucei rhodesiense / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity*; D014643:Variant Surface Glycoproteins, Trypanosoma / Q000235:genetics / Q000502:physiology
D008562:Membrane Glycoproteins; D021382:Protein Sorting Signals; D015800:Protozoan Proteins; D014643:Variant Surface Glycoproteins, Trypanosoma; C403774:serum resistance associated protein, Trypanosoma brucei