Characterization of a compensatory mutant of Leishmania major that lacks ether lipids but exhibits normal growth, and G418 and hygromycin resistance

Experimental Parasitology

Volumn 130, Issue 3, 2012, Pages 200-204

  Zufferey, Rachel ^a   Bibis, Stergios S ^a   Zhu, Tongtong ^a   Dhalladoo, Subbhalakshmi ^a  

^a ST JOHN'S UNIVERSITY   (United States)

Author keywords

Aminoglycoside resistance; Compensatory mutant; Dihydroxyacetonephosphate acyltransferase; Ether glycerolipid; Leishmania major; Virulence

Indexed keywords

AGAROSE; AMINOGLYCOSIDE ANTIBIOTIC AGENT; ANTIBIOTIC G 418; BLASTICIDIN; DIHYDROXYACETONE PHOSPHATE ACYLTRANSFERASE; ETHER LIPID; GENOMIC DNA; HYGROMYCIN; LIPOPHOSPHOGLYCAN; MILTEFOSINE; PROTEIN GP63; PROTEINASE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBIOTIC RESISTANCE; ANTIBIOTIC SENSITIVITY; ARTICLE; CONTROLLED STUDY; DNA DETERMINATION; ENZYME ACTIVITY; ENZYME SPECIFICITY; GENE AMPLIFICATION; GENE MUTATION; GROWTH CURVE; LEISHMANIA MAJOR; LEISHMANIASIS; MOLECULAR CLONING; MOUSE; MUTANT; NONHUMAN; PARASITE VIRULENCE; PRIORITY JOURNAL; REVERTANT; SURVIVAL; WILD TYPE;

ACYLTRANSFERASES; ANIMALS; ANTIPROTOZOAL AGENTS; CINNAMATES; DRUG RESISTANCE; GENE AMPLIFICATION; GENTAMICINS; GLYCOSPHINGOLIPIDS; HYGROMYCIN B; LEISHMANIA MAJOR; MEMBRANE PROTEINS; METALLOENDOPEPTIDASES; MICE; MICE, INBRED BALB C; MUTATION; PHOSPHOLIPID ETHERS; PROTEOGLYCANS; PROTOZOAN PROTEINS; VIRULENCE;

LEISHMANIA MAJOR; MUS;

EID: 84857456864     PISSN: 00144894     EISSN: 10902449     Source Type: Journal    
DOI: 10.1016/j.exppara.2012.01.008     Document Type: Article

References (32)

1. Beach D.H., Holz G.G., Anekwe G.E. Lipids of Leishmania promastigotes. Journal of Parasitology 1979, 65:201-216.
2. Beverley S.M. Gene amplification in Leishmania. Annual Review of Microbiology 1991, 45:417-444.
3. Chaudhuri G., Banerjee A.B. Lipids & fatty acids of Leishmania donovani donovani promastigotes. Indian Journal of Medical Research 1987, 85:140-148.
4. Connell N.D., Medina-Acosta E., McMaster W.R., Bloom B.R., Russell D.G. Effective immunization against cutaneous leishmaniasis with recombinant bacille Calmette-Guerin expressing the Leishmania surface proteinase gp63. Proceedings of the National Academy of Sciences of the United States of America 1993, 90:11473-11477.
5. de Vet E.C., Hilkes Y.H., Fraaije M.W., van den Bosch H. Alkyl-dihydroxyacetonephosphate synthase. Presence and role of flavin adenine dinucleotide. Journal of Biological Chemistry 2000, 275:6276-6283.
6. Descoteaux A., Avila H.A., Zhang K., Turco S.J., Beverley S.M. Leishmania LPG3 encodes a GRP94 homolog required for phosphoglycan synthesis implicated in parasite virulence but not viability. EMBO Journal 2002, 21:4458-4469.
7. Descoteaux A., Turco S.J. Functional aspects of the Leishmania donovani lipophosphoglycan during macrophage infection. Microbes and Infection 2002, 4:975-981.
8. Feng X., Rodriguez-Contreras D., Buffalo C., Bouwer H.G., Kruvand E., Beverley S.M., Landfear S.M. Amplification of an alternate transporter gene suppresses the avirulent phenotype of glucose transporter null mutants in Leishmania mexicana. Molecular Microbiology 2009, 71:369-381.
9. Ferguson M.A. The surface glycoconjugates of trypanosomatid parasites. Philosophical Transactions of the Royal Society of London; Series B; Biological Sciences 1997, 352:1295-1302.
10. Hajra A.K. Glycerolipid biosynthesis in peroxisomes (microbodies). Progress in Lipid Research 1995, 34:343-364.
11. Hajra A.K., Bishop J.E. Glycerolipid biosynthesis in peroxisomes via the acyl dihydroxyacetone phosphate pathway. Annals of the New York Academy of Sciences 1982, 386:170-182.
12. Ilg T. Lipophosphoglycan of the protozoan parasite Leishmania: stage- and species-specific importance for colonization of the sandfly vector, transmission and virulence to mammals. Medical Microbiology and Immunology (Berl) 2001, 190:13-17.
13. Ilg T., Stierhof Y.D., Craik D., Simpson R., Handman E., Bacic A. Purification and structural characterization of a filamentous, mucin-like proteophosphoglycan secreted by Leishmania parasites. Journal of Biological Chemistry 1996, 271:21583-21596.
14. Ilgoutz S.C., McConville M.J. Function and assembly of the Leishmania surface coat. International Journal of Parasitology 2001, 31:899-908.
15. Ivanetich K.M., Santi D.V. Bifunctional thymidylate synthase-dihydrofolate reductase in protozoa. FASEB Journal 1990, 4:1591-1597.
16. Ivanetich K.M., Santi D.V. Thymidylate synthase-dihydrofolate reductase in protozoa. Experimental Parasitology 1990, 70:367-371.
17. Kelleher M., Bacic A., Handman E. Identification of a macrophage-binding determinant on lipophosphoglycan from Leishmania major promastigotes. Proceedings of the National Academy of Sciences of the United States of America 1992, 89:6-10.
18. Liu D., Nagan N., Just W.W., Rodemer C., Thai T.P., Zoeller R.A. Role of dihydroxyacetonephosphate acyltransferase in the biosynthesis of plasmalogens and non-ether glycerolipids. Journal of Lipid Research 2005, 46:727-735.
19. Matlashewski G. Leishmania infection and virulence. Medical Microbiology and Immunology (Berl) 2001, 190:37-42.
20. McConville M.J., Thomas-Oates J.E., Ferguson M.A., Homans S.W. Structure of the lipophosphoglycan from Leishmania major. Journal of Biological Chemistry 1990, 265:19611-19623.
21. Medina-Acosta E., Cross G.A. Rapid isolation of DNA from trypanosomatid protozoa using a simple 'mini-prep' procedure. Molecular and Biochemical Parasitology 1993, 59:327-329.
22. Naderer T., Vince J.E., McConville M.J. Surface determinants of Leishmania parasites and their role in infectivity in the mammalian host. Current Molecular Medicine 2004, 4:649-665.
23. Nare B., Luba J., Hardy L.W., Beverley S. New approaches to Leishmania chemotherapy: pteridine reductase 1 (PTR1) as a target and modulator of antifolate sensitivity. Parasitology 1997, 114(Suppl.):S101-S110.
24. Ouellette M., Borst P. Drug resistance and P-glycoprotein gene amplification in the protozoan parasite Leishmania. Research in Microbiology 1991, 142:737-746.
25. Sacks D.L. Leishmania-sand fly interactions controlling species-specific vector competence. Cellular Microbiology 2001, 3:189-196.
26. Schneider P., Ferguson M.A., McConville M.J., Mehlert A., Homans S.W., Bordier C. Structure of the glycosyl-phosphatidylinositol membrane anchor of the Leishmania major promastigote surface protease. Journal of Biological Chemistry 1990, 265:16955-16964.
27. Segovia M. Leishmania gene amplification: a mechanism of drug resistance. Annals of Tropical Medicine and Parasitology 1994, 88:123-130.
28. Wassef M.K., Fioretti T.B., Dwyer D.M. Lipid analyses of isolated surface membranes of Leishmania donovani promastigotes. Lipids 1985, 20:108-115.
29. Zufferey R., Al-Ani G.K., Dunlap K. Leishmania dihydroxyacetonephosphate acyltransferase LmDAT is important for ether lipid biosynthesis but not for the integrity of detergent resistant membranes. Molecular and Biochemical Parasitology 2009, 168:177-185.
30. Zufferey R., Allen S., Barron T., Sullivan D.R., Denny P.W., Almeida I.C., Smith D.F., Turco S.J., Ferguson M.A., Beverley S.M. Ether phospholipids and glycosylinositolphospholipids are not required for amastigote virulence or for inhibition of macrophage activation by Leishmania major. Journal of Biological Chemistry 2003, 278:44708-44718.
31. Zufferey R., Mamoun C.B. Leishmania major expresses a single dihydroxyacetone phosphate acyltransferase localized in the glycosome, important for rapid growth and survival at high cell density and essential for virulence. Journal of Biological Chemistry 2006, 281:7952-7959.
32. Zufferey R., Mamoun C.B. The initial step of glycerolipid metabolism in Leishmania major promastigotes involves a single glycerol-3-phosphate acyltransferase enzyme important for the synthesis of triacylglycerol but not essential for virulence. Molecular Microbiology 2005, 56:800-810.