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.
Vanhamme
Luc
L
Laboratory of Molecular Parasitology, Department of Molecular Biology, IBMM, Free University of Brussels, 12, rue des Professeurs Jeener et Brachet, B-6041 Gosselies, Belgium.
Renauld
Hubert
H
Lecordier
Laurence
L
Poelvoorde
Philippe
P
Van Den Abbeele
Jan
J
Pays
Etienne
E
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