Hostname: page-component-cd9895bd7-fscjk Total loading time: 0 Render date: 2024-12-18T14:04:49.221Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  14 September 2004

C. M. R. TURNER ,
S. McLELLAN ,
L. A. G. LINDERGARD ,
L. BISONI ,
A. TAIT  and
A. MacLEOD
C. M. R. TURNER
Affiliation:
Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, UK
S. McLELLAN
Affiliation:
Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, UK
L. A. G. LINDERGARD
Affiliation:
Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, UK
L. BISONI
Affiliation:
Division of Infection and Immunity, Institute of Biomedical and Life Sciences, Joseph Black Building, University of Glasgow, Glasgow, G12 8QQ, UK Current address: Wellcome Centre for Cell Biology, University of Edinburgh, Michael Swann Building, King's Building, Edinburgh EH9 3JR, UK.
A. TAIT
Affiliation:
Wellcome Centre for Molecular Parasitology, Anderson College, University of Glasgow, 56 Dumbarton Road, Glasgow G11 6NU, UK
A. MacLEOD
Affiliation:
Wellcome Centre for Molecular Parasitology, Anderson College, University of Glasgow, 56 Dumbarton Road, Glasgow G11 6NU, UK
Get access Rights & Permissions [Opens in a new window]

Abstract

Some Trypanosoma brucei lines infect humans whereas others do not because the parasites are lysed by human serum. We have developed a robust, quantitative in vitro assay based on differential uptake of fluorescent dyes by live and dead trypanosomes to quantify the extent and kinetics of killing by human serum. This method has been used to discriminate between 3 classes of human serum resistance; sensitive, resistant and intermediate. TREU 927/4, the parasite used for the T. brucei genome project, is intermediate. The phenotype is expressed in both bloodstream and metacyclic forms, is stably expressed during chronic infections and on cyclical transmission through tsetse flies. Trypanosomes of intermediate phenotype are distinguished from sensitive populations of cells by the slower rate of lysis and by the potential to become fully resistant to killing by human serum as a result of selection or long-term serial passaging in mice, and to pass on full resistance phenotype to its progeny in a genetic cross. The sra gene has been shown previously to determine human serum resistance in T. brucei but screening for the presence and expression of this gene indicated that it is not responsible for the human serum resistance phenotype in the trypanosome lines that we have examined, indicating that an alternative mechanism for HSR exists in these stocks. Examination of the inheritance of the phenotype in F1 hybrids for both bloodstream and metacyclic stages from 2 genetic crosses demonstrated that the phenotype is co-inherited in both life-cycle stages in a manner consistent with being a Mendelian trait, determined by only one or a few genes.

Keywords

Trypanosoma bruceigenome projecthuman infectivityhuman serum resistance
Type
Research Article
Information
Parasitology , Volume 129 , Issue 4 , October 2004 , pp. 445 - 454
Copyright
2004 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

AGBO, E. C., CLAUSEN, P-H., BUSCHER, P., MAJIWA, P. A. O., CLAAASSEN, E. & TE PAS, M. F. W. (2003). Population genetic structure and cladistic analysis of Trypanosoma brucei isolates. Infection, Genetics and Evolution 3, 165–174.CrossRefGoogle Scholar
BERBEROF, M., PEREZ-MORGA, D. & PAYS, E. (2001). A receptor-like flagellar pocket glycoprotein specific to Trypanosoma brucei gambiense. Molecular and Biochemical Parasitology 113, 127–138.CrossRefGoogle Scholar
BRUN, R. & JENNI, L. (1987). Human serum resistance of metacyclic forms of Trypanosoma brucei brucei, T. brucei rhodesiense and T. brucei gambiense. Parasitology Research 73, 218–223.Google Scholar
CAMPILLO, N. & CARRINGTON, M. (2003). The origin of the human serum resistance associated (SRA) gene and a model of the structure of the SRA polypeptide from Trypanosoma brucei rhodesiense. Molecular and Biochemical Parasitology 127, 79–84.CrossRefGoogle Scholar
DE GREEF, C. & HAMERS, R. (1994). The serum-resistance associated (SRA) gene of Trypanosoma brucei rhodesiense encodes a VSG-like protein. Molecular and Biochemical Parasitology 68, 277–284.CrossRefGoogle Scholar
EL-SAYED, N. M. A., GHEDIN, E., SONG, J., MacLEOD, A., BRINGAUD, F., LARKIN, C., WANLESS, D., PETERSON, J., HOU, L., TAYLOR, S., TWEEDIE, A., BITEAU, N., KHALAK, H. G., LIN, X., MASON, T., HANNICK, L., CALER, E., BLANDIN, G., BARTHOLOMEU, D., SIMPSON, A. J., KAUL, S., ZHAO, H., PAI, G., VAN AKEN, S., UTTERBACK, T., HAAS, B., KOO, H. L., UMAYAM, L., SUH, B., GERRARD, C., LEECH, V., QI, R., SCHWARTZ, D., FELDBLYUM, T., SALZBERG, S., TAIT, A., TURNER, C. M. R., ULLU, E., WHITE, O., MELVILLE, S., ADAMS, M. D., FRASER, C. M. & DONELSON, J. E. (2003). The sequence and analysis of Trypanosoma brucei chromosome II. Nucleic Acids Research 31, 4856–4863.CrossRefGoogle Scholar
GHIOTTO, V., BRUN, R., JENNI, L. & HECKER, H. (1979). Trypanosoma brucei: morphometric changes and loss of infectivity during transformation of bloodstream forms to procyclic culture forms in vitro. Experimental Parasitology 48, 447–456.CrossRefGoogle Scholar
GIBSON, W. C. (1986). Will the real Trypanosoma b. gambiense please stand up. Parasitology Today 2, 255–257.CrossRefGoogle Scholar
GIBSON, W. (2002). Will the real Trypanosoma brucei rhodesiense please step forward? Trends in Parasitology 18, 486–490.Google Scholar
GIBSON, W., BACKHOUSE, T. & GRIFFITHS, A. (2002). The human serum-resistance associated gene is ubiquitous and conserved in Trypanosoma brucei rhodesiense throughout East Africa. Infection, Genetics and Evolution 1, 207–214.CrossRefGoogle Scholar
GODFREY, D. G., BAKER, R. D., RICKMAN, L. R. & MEHLITZ, D. (1990). The distribution, relationships and identification of enzymatic variants within the subgenus Trypanozoon. Advances in Parasitology 29, 1–74.Google Scholar
GRAHAM, S. V., MATTHEWS, K. R., SHIELS, P. G. & BARRY, J. D. (1990). Distinct, developmental stage-specific activation mechanisms of trypanosome VSG genes. Parasitology 101, 361–367.CrossRefGoogle Scholar
HAJDUK, S. L., MOORE, D. R., VASUDEVACHARYA, J., SIQUEIRA, H., TORRI, A. F., TYTLER, E. M. & ESKO, J. D. (1989). Lysis of Trypanosoma brucei by a toxic subspecies of human high density lipoprotein. Journal of Biological Chemistry 264, 5210–5217.Google Scholar
HALL, N., BERRIMAN, M., LENNARD, N. J., HARRIS, B. R., BART-DELABESSE, E. N., HERTZ-FOWLER, C., GERRARD, C. S., ATKIN, R. J., BARRON, A. J., BOWMAN, S., BRAY-ALLEN, S. P., BRINGAUD, F., CLARK, L. N., CORTON, C. H., CRONIN, A., DAVIES, R., DOGGETT, J., FRASER, A., GRUTER, E., HALL, S., HARPER, A. D., KAY, M. P., LEECH, V., MAYES, R., PRICE, C., QUAIL, M. A., RABBINOWITSCH, E., REITTER, C., RUTHERFORD, K., SASSE, J., SHARP, S., SHOWNKEEN, R., MacLEOD, A., TAYLOR, S., TWEEDIE, A., TURNER, C. M. R., TAIT, A., GULL, K., BARRELL, B. & MELVILLE, S. (2003). The DNA sequence of chromosome I of an African trypanosome: gene content, chromosome organisation, recombination and polymorphism. Nucleic Acids Research 31, 4864–4873.CrossRefGoogle Scholar
HAWKING, F. (1977). The resistance to human plasma of Trypanosoma brucei, T. rhodesiense and T. gambiense. 1. Analysis of the composition of trypansome strains. Transactions of the Royal Society of Tropical Medicine and Hygiene 70, 504–512.Google Scholar
HIDE, G., WELBURN, S. C., TAIT, A. & MAUDLIN, I. (1994). Epidemiological relationships of Trypanosoma brucei stocks from South East Uganda: evidence for different population structures in human infective and non-human infective isolates. Parasitology 109, 95–111.CrossRefGoogle Scholar
HOARE, C. A. (1972). The Trypanosomes of Mammals. Blackwell Scientific Publications, Oxford.
LANHAM, S. M. & GODFREY, D. G. (1970). Isolation of salivarian trypanosomes from man and other mammals using DEAE-cellulose. Experimental Parasitology 28, 521–534.CrossRefGoogle Scholar
MacLEOD, A., TURNER, C. M. R. & TAIT, A. (1997). Detection of single copy gene sequences from single trypanosomes. Molecular and Biochemical Parasitology 84, 267–270.CrossRefGoogle Scholar
MacLEOD, A., TURNER, C. M. R. & TAIT, A. (1999). A high level of mixed Trypanosoma brucei infections in tsetse flies detected by three hypervariable minisatellites. Molecular and Biochemical Parasitology 102, 237–248.CrossRefGoogle Scholar
MacLEOD, A., TWEEDIE, A., WELBURN, S. C., MAUDLIN, S. C., MAUDLIN, I., TURNER, C. M. R. & TAIT, A. (2000). Minisatellite marker analysis of Trypanosoma brucei: reconciliation of clonal, panmictic, and epidemic population genetic structures. Proceedings of the National Academy of Sciences, USA 97, 13442–13447.CrossRefGoogle Scholar
MATHIEU-DAUDE, F., STEVENS, J., WELSH, J., TIBAYRENC, M. & McCLELLAND, M. (1995). Genetic diversity and population structure of Trypanosoma brucei: clonality versus sexuality. Molecular and Biochemical Parasitology 72, 89–101.CrossRefGoogle Scholar
MILNER, J. D. & HAJDUK, S. L. (1999). Expression and localization of serum resistance associated protein in Trypanosoma brucei rhodesiense. Molecular and Biochemical Parasitology 30, 271–283.CrossRefGoogle Scholar
RADWANSKA, M., CHAMEKH, M., VANHAMME, L., CLAES, F., MAGEZ, S., MAGNUS, E., BAETSELIER, P., BUSCHER, P. & PAYS, E. (2002). The serum resistance-associated gene as a diagnostic tool for the detection of Trypanosoma brucei rhodesiense. American Journal of Tropical Medicine and Hygiene 67, 684–690.CrossRefGoogle Scholar
RICKMAN, L. R. & ROBSON, J. (1970 a). The blood incubation infectivity tests: a simple test which may serve to distinguish Trypanosoma brucei from T. rhodesiense. Bulletin of the World Health Organization 42, 650–651.Google Scholar
RICKMAN, L. R. & ROBSON, J. (1970 b). The testing of proven Trypanosoma brucei and T. rhodesiense strains by the Blood Incubation Test. Bulletin of the World Health Organization 42, 911–916.Google Scholar
RIFKIN, M. R., DE GREEF, C., JIWA, A., LANDSBERGER, F. R. & SHAPIRO, S. Z. (1994). Human serum-sensitive Trypanosoma brucei rhodesiense: a comparison with serologically identical human serum-resistant clones. Molecular and Biochemical Parasitology 66, 211–220.CrossRefGoogle Scholar
SAMBROOK, J., FRITSCH, E. F. & MANIATIS, T. (1989). Molecular Cloning: A Laboratory Manual, 2nd Edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York.
TAIT, A., BABIKER, E. A. & LERAY, D. (1984). Enzyme variation in T. brucei spp. I. Evidence for the sub-speciation of T. b. gambiense. Parasitology 89, 311–326.Google Scholar
TAIT, A., BARRY, J. D., WINK, R., SANDERSON, A. & CROWE, J. S. (1985). Enzyme variation in Trypanosome brucei spp. II. Evidence for T. b. rhodesiense being a set of variants of T. b. brucei. Parasitology 90, 89–100.Google Scholar
TAIT, A., MASIGA, D., OUMA, J., MacLEOD, A., SASSE, J., MELVILLE, S., LINDEGARD, G., McINTOSH, A. & TURNER, C. M. R. (2002). Genetic analysis of phenotype in Trypanosoma brucei: a classical approach to potentially complex traits. Phil. Transactions of the Royal Society of London B 357, 89–99.Google Scholar
TOMLINSON, S., JANSEN, A-M., KOUDINOV, A., GHISO, J. A., MIURA, N-H. C., RIFKIN, M. R., OHTAKI, S. & NUSSENZWEIG, V. (1995). High-density-lipoprotein-independent killing of Trypanosoma brucei by human serum. Molecular and Biochemical Parasitology 70, 131–138.CrossRefGoogle Scholar
TURNER, C. M. R., ASLAM, N., SMITH, E., BUCHANAN, N. & TAIT, A. (1991). The effects of genetic exchange on variable antigen expression in Trypanosoma brucei. Parasitology 103, 379–386.CrossRefGoogle Scholar
TURNER, C. M. R., STERNBERG, J., BUCHANAN, N., SMITH, E., HIDE, G. & TAIT, A. (1990). Evidence that the mechanism of gene exchange in Trypanosoma brucei involves meiosis and syngamy. Parasitology 101, 377–386.CrossRefGoogle Scholar
VAN DEURSEN, F. J., SHAHI, S. K., TURNER, C. M. R., HARTMANN, C., GUERRA-GIRALDEZ, C., MATTHEWS, K. R. & CLAYTON, C. E. (2001). Characterization of the growth and differentiation in vivo and in vitro of bloodstream-form Trypanosoma brucei TREU 927. Molecular and Biochemical Parasitology 112, 163–171.CrossRefGoogle Scholar
WELBURN, S. C., PICOZZI, K., FEVRE, E. M., COLEMAN, P. G., ODIIT, M., CARRINGTON, M. & MAUDLIN, I. (2001). Identification of human-infective trypanosomes in animal reservoir of sleeping sickness in Uganda by means of serum-resistance-associated (SRA) gene. Lancet 358, 2017–2019.CrossRefGoogle Scholar
XONG, H. V., VANHAMME, L., CHAMEKH, M., CHIMFWEMBE, C. E., VAN DEN ABBEELE, J., PAYS, A., VAN MEIRVENNE, N., HAMERS, R., DE BAETSELIER, P. & PAYS, E. (1998). A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense. Cell 95, 839–846.CrossRefGoogle Scholar