Functional characterization of the hexose transporter Hxt13p: An efflux pump that mediates resistance to miltefosine in yeast

Fungal Genetics and Biology

Volumn 61, Issue , 2013, Pages 23-32

  Biswas, Chayanika ^a   Djordjevic, Julianne T ^a   Zuo, Xiaoming ^a   Boles, Eckhard ^d   Jolliffe, Katrina A ^c   Sorrell, Tania C ^a,b   Chen, Sharon C A ^a,b  

^a WESTMEAD HOSPITAL   (Australia)

^b UNIVERSITY OF SYDNEY   (Australia)

^c UNIVERSITY OF SYDNEY   (Australia)

^d GOETHE UNIVERSITY   (Germany)

Author keywords

Efflux pump; Hexose transporter; HXT13; Miltefosine; Overexpression; Resistance

Indexed keywords

ADENOSINE TRIPHOSPHATE; AMPHOTERICIN B; CYCLOHEXIMIDE; ECHINOCANDIN; GLUCOSE TRANSPORTER; HEXOSE; HXT13 PROTEIN; MILTEFOSINE; PYRROLE; SULFOMETURON METHYL; UNCLASSIFIED DRUG;

ANTIFUNGAL RESISTANCE; ARTICLE; CELL VIABILITY; CONTROLLED STUDY; DRUG EXPOSURE; DRUG TRANSPORT; FLOW CYTOMETRY; FUNGAL GENE; FUNGAL GENOME; FUNGAL STRAIN; GENE FUNCTION; GENE IDENTIFICATION; GENE LIBRARY; GENE OVEREXPRESSION; GENETIC ASSOCIATION; GENETIC SCREENING; HXT13 GENE; HXT14 GENE; HXT15 GENE; HXT17 GENE; IMMUNOCYTOCHEMISTRY; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; SACCHAROMYCES CEREVISIAE; SUGAR TRANSPORT;

FUNGI; SACCHAROMYCES CEREVISIAE;

EFFLUX PUMP; HEXOSE TRANSPORTER; HXT13; MILTEFOSINE; OVEREXPRESSION; RESISTANCE;

ANTIFUNGAL AGENTS; DRUG RESISTANCE, FUNGAL; GENE EXPRESSION; MICROBIAL VIABILITY; MONOSACCHARIDE TRANSPORT PROTEINS; PHOSPHORYLCHOLINE; SACCHAROMYCES CEREVISIAE;

EID: 84887819261     PISSN: 10871845     EISSN: 10960937     Source Type: Journal    
DOI: 10.1016/j.fgb.2013.09.005     Document Type: Article

References (39)

1. Albertson G.D., Niimi M., Cannon R.D., Jenkinson H.F. Multiple efflux mechanisms are involved in Candida albicans fluconazole resistance. Antimicrob. Agents Chemother. 1996, 40:2835-2841.
2. Barker K.S., Rogers P.D. Recent insights into the mechanisms of antifungal resistance. Curr. Infect Dis. Rep. 2006, 8:449-456.
3. Boles E., Hollenberg C.P. The molecular genetics of hexose transport in yeasts. FEMS Microbiol. Rev. 1997, 21:85-111.
4. Cannon R.D., Lamping E., Holmes A.R., Niimi K., Baret P.V., Keniya M.V., Tanabe K., Niimi M., Goffeau A., Monk B.C. Efflux-mediated antifungal drug resistance. Clin. Microbiol. Rev. 2009, 22:291-321.
5. Cannon R.D., Lamping E., Holmes A.R., Niimi K., Tanabe K., Niimi M., Monk B.C. Candida albicans drug resistance another way to cope with stress. Microbiology 2007, 153:3211-3217.
6. Castro C., Serrano M.C., Flores B., Espinel-Ingroff A., Martin-Mazuelos E. Comparison of the Sensititre YeastOne colorimetric antifungal panel with a modified NCCLS M38-A method to determine the activity of voriconazole against clinical isolates of Aspergillus spp. J. Clin. Microbiol. 2004, 42:4358-4360.
7. Chen S.C., Sorrell T.C. Antifungal agents. Med. J. Aust. 2007, 187:404-409.
8. Chen X.J., Guan M.X., Clark-Walker G.D. MGM101, a nuclear gene involved in maintenance of the mitochondrial genome in Saccharomyces cerevisiae. Nucleic Acids Res. 1993, 21:3473-3477.
9. Coelho A.C., Boisvert S., Mukherjee A., Leprohon P., Corbeil J., Ouellette M. Multiple mutations in heterogeneous miltefosine-resistant Leishmania major population as determined by whole genome sequencing. PLoS Negl. Trop. Dis. 2012, 6:e1512.
10. Croft S.L., Seifert K., Duchene M. Antiprotozoal activities of phospholipid analogues. Mol. Biochem. Parasitol. 2003, 126:165-172.
11. de Castroa S.L., Santa-Ritaa R.M., Urbinab J.A., Croftc S.L. Antiprotozoal lysophospholipid analogues: a comparison of their activity against trypanosomatid parasites and tumor cells. Mini. Rev. Med. Chem. 2004, 4:141-151.
12. Dorlo T.P., Balasegaram M., Beijnen J.H., de Vries P.J. Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J. Antimicrob. Chemother. 2012, 67:2576-2597.
13. Dorlo T.P., van Thiel P.P., Huitema A.D., Keizer R.J., de Vries H.J., Beijnen J.H., de Vries P.J. Pharmacokinetics of miltefosine in Old World cutaneous leishmaniasis patients. Antimicrob. Agents Chemother. 2008, 52:2855-2860.
14. Espinel-Ingroff A. Mechanisms of resistance to antifungal agents: yeasts and filamentous fungi. Rev. Iberoam. Micol. 2008, 25:101-106.
15. Hanson P.K., Malone L., Birchmore J.L., Nichols J.W. Lem3p is essential for the uptake and potency of alkylphosphocholine drugs, edelfosine and miltefosine. J. Biol. Chem. 2003, 278:36041-36050.
16. Janvier F. Treatment of leishmaniasis: institut pasteur, Paris. Med. Trop. (Mars) 2008, 68:584-585.
17. Kanafani Z.A., Perfect J.R. Antimicrobial resistance: resistance to antifungal agents: mechanisms and clinical impact. Clin. Infect. Dis. 2008, 46:120-128.
18. Maltezou H.C. Drug resistance in visceral leishmaniasis. J. Biomed. Biotechnol. 2010, 2010:617521.
19. Marger M.D., Saier M.H. A major superfamily of transmembrane facilitators that catalyse uniport, symport and antiport. Trends Biochem. Sci. 1993, 18:13-20.
20. Marian T., Balkay L., Tron L., Krasznai Z.T., Szabo-Peli J., Krasznai Z. Effects of miltefosine on membrane permeability and accumulation of [99mTc]-hexakis-2-methoxyisobutyl isonitrile, 2-[18F]fluoro-2-deoxy-D-glucose, daunorubucin and rhodamine123 in multidrug-resistant and sensitive cells. Eur. J. Pharm. Sci. 2005, 24:495-501.
21. Menez C., Buyse M., Dugave C., Farinotti R., Barratt G. Intestinal absorption of miltefosine: contribution of passive paracellular transport. Pharm. Res. 2007, 24:546-554.
22. Nakamura K., Niimi M., Niimi K., Holmes A.R., Yates J.E., Decottignies A., Monk B.C., Goffeau A., Cannon R.D. Functional expression of Candida albicans drug efflux pump Cdr1p in a Saccharomyces cerevisiae strain deficient in membrane transporters. Antimicrob. Agents Chemother. 2001, 45:3366-3374.
23. Nourani A., Wesolowski-Louvel M., Delaveau T., Jacq C., Delahodde A. Multiple-drug-resistance phenomenon in the yeast Saccharomyces cerevisiae: involvement of two hexose transporters. Mol. Cell. Biol. 1997, 17:5453-5460.
24. Ouedraogo J.P., Hagen S., Spielvogel A., Engelhardt S., Meyer V. Survival strategies of yeast and filamentous fungi against the antifungal protein AFP. J. Biol. Chem. 2011, 286:13859-13868.
25. Panwar S.L., Pasrija R., Prasad R. Membrane homoeostasis and multidrug resistance in yeast. Biosci. Rep. 2008, 28:217-228.
26. Pao S.S., Paulsen I.T., Saier M.H. Major facilitator superfamily. Microbiol. Mol. Biol. Rev. 1998, 62:1-34.
27. Perez-Victoria F.J., Gamarro F., Ouellette M., Castanys S. Functional cloning of the miltefosine transporter. A novel P-type phospholipid translocase from Leishmania involved in drug resistance. J. Biol. Chem. 2003, 278:49965-49971.
28. Perez-Victoria F.J., Sanchez-Canete M.P., Seifert K., Croft S.L., Sundar S., Castanys S., Gamarro F. Mechanisms of experimental resistance of Leishmania to miltefosine: implications for clinical use. Drug Resist. Updat. 2006, 9:26-39.
29. Perlin D.S. Antifungal drug resistance: do molecular methods provide a way forward?. Curr. Opin. Infect. Dis. 2009, 22:568-573.
30. Saier M.H., Beatty J.T., Goffeau A., Harley K.T., Heijne W.H., Huang S.C., Jack D.L., Jahn P.S., Lew K., Liu J., Pao S.S., Paulsen I.T., Tseng T.T., Virk P.S. The major facilitator superfamily. J. Mol. Microbiol. Biotechnol. 1999, 1:257-279.
31. Sambrook J., Russell D.W. Molecular Cloning: A Laboratory Manual 2001, vol. 1. Cold Spring Harbor Laboratory, Cold Spring Harbor Laboratory Press, NY.
32. Sundriyal S., Sharma R.K., Jain R. Current advances in antifungal targets and drug development. Curr. Med. Chem. 2006, 13:1321-1335.
33. Tong Z., Widmer F., Sorrell T.C., Guse Z., Jolliffe K.A., Halliday C., Lee O.C., Kong F., Wright L.C., Chen S.C. In vitro activities of miltefosine and two novel antifungal biscationic salts against a panel of 77 dermatophytes. Antimicrob. Agents Chemother. 2007, 51:2219-2222.
34. Unger C., Fleer E., Damenz W., Hilgard P., Nagel G., Eibl H. Hexadecylphosphocholine: determination of serum concentrations in rats. J. Lipid Mediat. 1991, 3:71-78.
35. van Blitterswijk W.J., Verheij M. Anticancer alkylphospholipids: mechanisms of action, cellular sensitivity and resistance, and clinical prospects. Curr. Pharm. Des. 2008, 14:2061-2074.
36. Widmer F., Wright L.C., Obando D., Handke R., Ganendren R., Ellis D.H., Sorrell T.C. Hexadecylphosphocholine (miltefosine) has broad-spectrum fungicidal activity and is efficacious in a mouse model of cryptococcosis. Antimicrob. Agents Chemother. 2006, 50:414-421.
37. Wieczorke R., Krampe S., Weierstall T., Freidel K., Hollenberg C.P., Boles E. Concurrent knock-out of at least 20 transporter genes is required to block uptake of hexoses in Saccharomyces cerevisiae. FEBS Lett. 1999, 464:123-128.
38. Zuo X., Djordjevic J.T., Bijosono Oei J., Desmarini D., Schibeci S.D., Jolliffe K.A., Sorrell T.C. Miltefosine induces apoptosis-like cell death in yeast via Cox9p in cytochrome c oxidase. Mol. Pharmacol. 2011, 80:476-485.
39. Zuo X., Xue D., Li N., Clark-Walker G.D. A functional core of the mitochondrial genome maintenance protein Mgm101p in Saccharomyces cerevisiae determined with a temperature-conditional allele. FEMS Yeast Res. 2007, 7:131-140.