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

Mol Biochem Parasitol. 2004 May;135(1):39-47. doi: 10.1016/j.molbiopara.2004.01.004.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Conserved Sequence
  • Gene Order
  • Genes, Protozoan
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / physiology
  • Molecular Sequence Data
  • Multigene Family
  • Phenotype
  • Protein Sorting Signals
  • Protozoan Proteins / chemistry
  • Protozoan Proteins / genetics*
  • Protozoan Proteins / physiology
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Serum
  • Trypanosoma brucei brucei / genetics*
  • Trypanosoma brucei brucei / growth & development
  • Trypanosoma brucei brucei / pathogenicity*
  • Trypanosoma brucei rhodesiense / genetics*
  • Trypanosoma brucei rhodesiense / growth & development
  • Trypanosoma brucei rhodesiense / pathogenicity*
  • Variant Surface Glycoproteins, Trypanosoma / genetics
  • Variant Surface Glycoproteins, Trypanosoma / physiology

Substances

  • Membrane Glycoproteins
  • Protein Sorting Signals
  • Protozoan Proteins
  • Variant Surface Glycoproteins, Trypanosoma
  • serum resistance associated protein, Trypanosoma brucei