The serum resistance-associated (SRA) gene of Trypanosoma brucei rhodesiense encodes a variant surface glycoprotein-like protein

Human infectivity trait in Trypanosoma brucei: stability, heritability and relationship to sra expression

“…The only occasions in which we have found the trait to be variable is under selection pressure and in the artificial laboratory situation of long-term serial passaging between mice (for intermediate and resistant, but not sensitive, lines). This variability has been noted before (De Greef and Hamers 1994;Hajduk et al 1989) and indeed has been exploited extremely successfully to create isogenic pairs of sensitive and resistant lines, comparison of which has led to the identification of a gene, sra, that can determine resistance/sensitivity (De Greef and Hamers;, Xong et al 1998Milner and Hajduk 1999). It is possible that the mechanism of variability is common to many stocks irrespective of whether a sra or non-sra mode of action is employed to determine human serum resistance.…”

“…However, while it is clear that the sra gene is responsible for human infectivity in a large number of T. b. rhodesiense isolates Welburn et al 2001), there are exceptions to this in trypanosome lines from East Africa (Rifkin et al 1994;Agbo et al 2003) and, critically, this gene is not present in West African T. b. gambiense isolates (De Greef and Hamers 1994;Radwanska et al 2002). Thus there must be alternative mechanisms determining human infectivity/human serum resistance other than those based on the sra gene.…”

In Vitro Generation of Human High-Density-Lipoprotein-Resistant Trypanosoma brucei brucei

“…The discovery of a human serum resistance-associated gene (SRA) in T. b. rhodesiense, but not in T. b. brucei, provided a molecular explanation for human infectivity by these parasites (9,10,11). Several experiments have shown a correlation between the expression of the SRA gene and resistance to human serum (11,35), and transfection of this gene into T. b. brucei conferred resistance to human serum and TLF (41,74).…”

“…Several experiments have shown a correlation between the expression of the SRA gene and resistance to human serum (11,35), and transfection of this gene into T. b. brucei conferred resistance to human serum and TLF (41,74). In addition, the SRA gene has proven to be a reliable marker for T. b. rhodesiense in epidemiological studies throughout East Africa (16,18,39,47,72,73).…”

“…Because of the similarities between T. b. rhodesiense and T. b. brucei, the origins of human serum resistance have been debated. However, it is generally thought that the SRA gene originated from a VSG gene in an ancestral, human serum-sensitive trypanosome (8,11).…”