Abstract
The growth of bloodstream forms ofTrypanosoma evansi in axenic culture was inhibited by incubation with 11-oxatetradecanoic acid (O-11), an analog of myristic acid. Parasites isolated from Asia, Africa and South America were affected to a similar extent in measurements using three different assay systems concerned with different aspects of trypanosome growth and metabolism. The concentration of O-11 that inhibited trypanosome growth by 50% (LD50) was 3.7±0.2 μM as measured by direct counting of survivors using a haemocytometer, 5.1±2.0 μM in a colorimetric test based on the formation of a formazan product, and 8.8±3.7 μM by estimation of pyruvate. The activity of the drug was enhanced by the addition of fatty-acid-free bovine serum albumin as a carrier protein to the culture medium at an optimal concentration of 5 mg/ml. Increasing amounts of the donor horse serum used for routine maintenance of these cultures, which is normally the only source of myristic acid for these trypanosomes, also affected the toxicity of the drug, in this case increasing the LD50.
Similar content being viewed by others
References
Brun R, Kunz C (1989) In vitro drug sensitivity test forTrypanosoma brucei subgroup bloodstream trypomastigotes. Acta Trop (Basel) 46:361–368
Clarkson AB Jr, Bienen EJ, Pollakis G, Saric M, McIntosh L, Grady RW (1990) Trypanosome alternative oxidase. Chemotherapy for trypanosomiasis. ILRAD, Nairobi
Clayton CE, Mowatt MR (1989) The procyclic acidic repetitive proteins ofTrypanosoma brucei. J Biol Chem 264:15088–15093
Dixon H (1967) Effects of trypanosome infection on rat plasma constituents. Trans R Soc Trop Med Hyg 61:12–13
Dixon H, Ginger CD, Williamson J (1971) The lipid metabolism of blood and culture forms ofTrypanosoma lewisi andTrypanosoma rhodesiense. Comp Biochem Physiol [B] 39:247–266
Doering TL, Masterson WJ, Hart GW, Englund PT (1990) Biosynthesis of glycosyl phosphatidylinositol membrane anchors. J Biol Chem 265:611–614
Doering TL, Raper J, Buxbaum LU, Adams SP, Gordon JI, Hart GW, Englund PT (1991) An analog of myristic acid with selective toxicity for African trypanosomes. Science 252:1851–1854
Field MC, Menon AK, Cross GAM (1991) A glycosylphosphatidylinositol protein anchor from procyclic stageTrypanosoma brucei: lipid structure and biosynthesis. EMBO J 10:2731–2739
Ferguson MAJ, Halder K, Cross GAM (1985)Trypanosoma brucei variant surface glycoprotein has asn-1,2-dimyristyl glycerol membrane anchor at its COOH-terminus. J Biol Chem 260:4963–4968
Giffin BF, McCann PP (1989) Physiological activation of the mitochondrion and the transformation capacity of DFMO induced intermediate and short stumpy bloodstream form trypanosomes. Am J Trop Med Hyg 40:487–493
Hamm B, Schindler A, Mecke D, Duszenko M (1990) Differentiation ofTrypanosoma brucei bloodstream trypomastigotes from long slender to short stumpy-like forms in axenic culture. Mol Biol Parasitol 40:13–22
Heuckeroth KO, Glaser L, Gordon JI (1988) Heteroatom substituted fatty acid analogs as substrates for N-myristoyltransferase: An approach for studying the enzymology and function of protein acylation. Proc Natl Acad Sci USA 85:8795–8799
Kishore NS, Lu T, Knoll LJ, Katoh A, Rudnick DA, Mehta PP, Adams SP, Devadas B, Huhn M, Atwood JL, Gotel GW, Gordon JI (1991) The substrate specificity ofSacchasomyces cerevisiae myristoyl CoA: protein N-myristoyl transferase. J Biol Chem 266:8835–8853
Low MG (1989) The glycosyl-phosphatidylinositol anchor of membrane proteins. BBA 988:427–454
McConville MJ (1991) Glycosylated phosphatidylinositols of the Trypanosomatidae. Biochemical protozoology. Taylor and Francis, London Washington, D.C.
Masterson WJ, Doering TL, Hart GW, Englund PT (1989) A novel pathway for glycon assembly: biosynthesis of the glycosylphosphatidylinositol anchor of the trypanosome variant surface glycoprotein. Cell 56:793–800
Masterson WJ, Raper J, Doering TL, Hart GW, Englund PT (1990) Fatty acid remodelling: a novel reaction sequence in the biosynthesis of trypanosome glycosyl phosphatidylinositol membrane anchors. Cell 62:73–80
Mellors A, Samad A (1989) The acquisition of lipids by African trypanosomes. Parasitol Today 5:239–244
Ross CA, Taylor AM (1991)Trypanosoma congolense: an in vitro assay to distinguish drug-resistant from drug-sensitive populations. Parasitol Res 76:326–331
Ross CA, Cardoso de Almeida ML, Turner MJ (1987) Variant surface glycoproteins ofTrypanosoma congolense bloodstream and metacyclic forms are anchored by a glycolipid tail. Mol Biochem Parasitol 22:153–158
Vickerman K (1965) The fine structure ofTrypanosoma congolense in its bloodstream phase. J Protozool 16:54–69
Zhang ZQ, Giroud C, Baltz T (1992) In vivo and in vitro sensitivity ofTrypanosoma evansi andT. equiperdum to diminazene, suramin, MelCy, quinapyramine and isometamidium. Acta Trop (Basel) 50:101–110
Zinsstag J, Brun R, Gessler M (1991) A new photometric assay for testing trypanocidal activity in vitro. Parasitol Res 77:33–38
Zweygarth E, Kaminsky R, Cheruiyot JK (1989) A simple and rapid method to initiateTrypanosoma brucei brucei andT. brucei bloodstream form cultures. Acta Trop (Basel) 46:205–206
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Ross, C.A., Taylor, A.M. Trypanocidal activity of a myristic acid analog in axenic cultures ofTrypanosoma evansi . Parasitol Res 80, 147–153 (1994). https://doi.org/10.1007/BF00933783
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00933783