Jd. Milner et Sl. Hajduk, Expression and localization of serum resistance associated protein in Trypanosoma brucei rhodesiense, MOL BIOCH P, 104(2), 1999, pp. 271-283
The trypanosome lyric factor (TLF) is a primate specific innate defense mec
hanism that restricts the host range of African trypanosomes. Trypanosoma b
rucei rhodesiense, the causative agent of the acute form of human sleeping
sickness, is resistant to the cytolytic action of TLF. By differential disp
lay PCR we have identified a gene in T. b. rhodesiense that is preferential
ly expressed in cell lines resistant to TLF. The protein sequence predicted
from the gene shows homology to the trypanosome variable surface glycoprot
ein (VSG) gene family and in particular, to the previously reported human s
erum resistance associated gene (SRA). The amount of SRA mRNA is over 1000-
fold higher in TLF resistant cells relative to TLF sensitive trypanosomes.
Treatment of TLF sensitive trypanosomes with increasing concentrations of T
LF in mice results in the selection of parasites that have reverted back to
the TLF resistant phenotype. These trypanosomes also showed high levels of
SRA mRNA. Antibodies against recombinant SRA react with a 59 kDa protein o
n western blots of total cell protein from TLF resistant trypanosomes but n
ot TLF sensitive cells. Indirect immunofluorescence revealed that SRA is a
cell surface protein present only in TLF resistant trypanosomes. These resu
lts suggest that TLF resistance in human sleeping sickness trypanosomes is
a consequence of the selective, high level expression of a cell surface mol
ecule(s). In addition, these studies support the role of TLF as a major fac
tor in human serum mediated killing of susceptible trypanosomes. (C) 1999 E
lsevier Science B.V. All rights reserved.