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Trk1, the sole potassium-specific transporter in Candida glabrata, contributes to the proper functioning of various cell processes

Abstract

Candida glabrata is a haploid yeast that is considered to be an emergent pathogen since it is the second most prevalent cause of candidiasis. Contrary to most yeasts, this species carries only one plasma membrane potassium transporter named CgTrk1. We show in this work that the activity of this transporter is regulated at the posttranslational level, and thus Trk1 contributes to potassium uptake under very different external cation concentrations. In addition to its function in potassium uptake, we report a diversity of physiological effects related to this transporter. CgTRK1 contributes to proper cell size, intracellular pH and membrane-potential homeostasis when expressed in Saccharomyces cerevisiae. Moreover, lithium influx experiments performed both in C. glabrata and S. cerevisiae indicate that the salt tolerance phenotype linked to CgTrk1 can be related to a high capacity to discriminate between potassium and lithium (or sodium) during the transport process. In summary, we show that CgTRK1 exerts a diversity of pleiotropic physiological roles and we propose that the corresponding protein may be an attractive pharmacological target for the development of new antifungal drugs.

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References

  1. Ariño J, Ramos J, Sychrová H (2010) Alkali metal cation transport and homeostasis in Yeasts. Microbiol Mol Biol Rev 74:95–120

  2. Ariño J, Ramos J, Sychrová H (2018) Monovalent cation transporters at the plasma membrane in yeasts. Yeast. https://doi.org/10.1002/yea.3355

  3. Benito B, Garciadeblás B, Schreier P, Rodriguez-Navarro A (2004) Novel p-type ATPases mediate high-affinity potassium or sodium uptake in fungi. Eukaryot Cell 3:359–368

  4. Bolotin-Fukuhara M, Fairhead C (2014) Candida glabrata: a deadly companion? Yeast 31:279–288

  5. Dujon B, Sherman D, Fischer G et al (2004) Genome evolution in yeasts. Nature 430:34–35

  6. Elicharová H, Hušeková B, Sychrová H (2016) Three Candida albicans potassium uptake systems differ in their ability to provide Saccharomyces cerevisiae trk1trk2 mutants with necessary potassium. FEMS Yeast Res 16:1–10

  7. Felcmanova K, Neveceralova P, Sychrova H, O (2017) Yeast Kch1 and Kch2 membrane proteins play a pleiotropic role in membrane potential establishment and monovalent cation homeostasis regulation. FEMS Yeast Res 17:fox053

  8. Fitzpatrick DA, Logue ME, Stajich JE, Butler G (2006) A fungal phylogeny based on 42 complete genomes derived from supertree and combined gene analysis. BMC Evol Biol 6:99

  9. Gabaldón T, Martin T, Marcet-Houben M et al (2013) Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genomics 14:623

  10. Gášková D, Brodská B, Heřman P, Vecer J, Malínský J, Sigler K, Benada O, Plásek J (1998) Fluorescent probing of membrane potential in walled cells: diS-C3(3) assay in Saccharomyces cerevisiae. Yeast 14:1189–1197

  11. Gómez M, Luyten K, Ramos J (1996) The capacity to transport potassium influences sodium tolerance in Saccharomyces cerevisiae. FEMS Microbiol Lett 135:157–160

  12. Hazen KC (1995) New and emerging yeast pathogens. Clin Microbiol Rev 8:462–478

  13. Hušeková B, Elicharová H, Sychrová H (2016) Pathogenic Candida species differ in the ability to grow at limiting potassium concentrations. Can J Microbiol 62:394–401

  14. Kodedová M, Sychrová H (2015) Changes in the sterol composition of the plasma membrane affect membrane potential, salt tolerance and the activity of multidrug resistance pumps in Saccharomyces cerevisiae. PLoS ONE 10:e0139306

  15. Llopis-Torregrosa V, Hušeková B, Sychrová H (2016) Potassium uptake mediated by Trk1 is crucial for Candida glabrata growth and fitness. PLoS ONE 11:e0153374

  16. Madrid R, Gómez MJ, Ramos J, Rodríguez-Navarro A (1998) Ectopic potassium uptake in trk1 trk2 mutants of Saccharomyces cerevisiae correlates with a highly hyperpolarized membrane potential. J Biol Chem 273:14838–14844

  17. Marešová L, Hošková BJ, Urbánková E, Chaloupka R, Sychrová H (2010) New applications of pHluorin—measuring intracellular pH of prototrophic yeasts and determining changes in the buffering capacity of strains with affected potassium homeostasis. Yeast 27:317–325

  18. Martínez J, Sychrova H, Ramos J (2011) Monovalent cations regulate expression and activity of the Hak1 potassium transporter in Debaryomyces hansenii. Fungal Genet Biol 48:177–184

  19. Navarrete C, Petrezsélyová S, Barreto L, Martínez JL, Zahrádka J, Ariño J, Sychrová H, Ramos J (2010) Lack of main K+ uptake systems in Saccharomyces cerevisiae cells affects yeast performance in both potassium-sufficient and potassium-limiting conditions. FEMS Yeast Res 10:508

  20. Perlroth J, Choi B, Spellberg B (2007) Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Med Mycol 45:321–346

  21. Prista C, Almagro A, Loureiro-Dias MC, Ramos J (1997) Physiological basis for the high salt tolerance of Debaryomyces hansenii. Appl Environm Microbiol 63:4005–4009

  22. Pueyo C, Jurado J, Prieto-Alamo MJ, Monje-Casas F, López-Barea J (2002) Multiplex reverse transcription-polymerase chain reaction for determining transcriptional regulation of thioredoxin and glutaredoxin pathways. Methods Enzymol 347:441–451

  23. Ramos J, Rodríguez-Navarro A (1986) Regulation and interconversion of the potassium transport systems of Saccharomyces cerevisiae as revealed by rubidium transport. Eur J Biochem 154:307–311

  24. Ramos J, Haro R, Rodríguez-Navarro A (1990) Regulation of potassium fluxes in Saccharomyces cerevisiae. BBA Biomembranes 1029:211–217

  25. Ramos J, Alijo R, Haro R, Rodríguez-Navarro A (1994) TRK2 is not a low-affinity potassium transporter in Saccharomyces cerevisiae. J Bacteriol 176:249–252

  26. Ramos J, Ariño J, Sychrová H (2011) Alkali–metal–cation influx and efflux systems in nonconventional yeast species. FEMS Microbiol Lett 317:1–8

  27. Ribeiro de Carvalho R, Chaves Silva N, Cusinato M, Tranches Dias KS, Dos Santos MH, Viegas Junior C, Gonçalves Silva É, Tranches Dias AL (2018) Promising synergistic activity of fluconazole with bioactive Guttiferone-A and derivatives against non-albicans Candida species. J Mycol Méd 28:645–650

  28. Rodriguez-Navarro A, Ramos J (1984) Dual system for potassium transport in Saccharomyces cerevisiae. J Bacteriol 159:940–945

  29. Shipston MJ (2014) Ion channel regulation by protein S-acylation. J Gen Physiol 143:659–678

  30. Xin H (2018) Effects of immune suppression in murine models of disseminated Candida glabrata and Candida tropicalis infection and utility of a synthetic peptide vaccine. Med Mycol 1:1. https://doi.org/10.1093/mmy/myy122

  31. Zayats V, Stockner T, Pandey SK, Wörz K, Ettrich R, Ludwig J (2015) A refined atomic scale model of the Saccharomyces cerevisiae K+-translocation protein Trk1p combined with experimental evidence confirms the role of selectivity filter glycines and other key residues. BBA Biomembranes 1848:1183–1195

  32. Zimmermannova O, Salzar A, Sychrova H, Ramos J (2015) The Zygosaccharomyces rouxii Trk1 is an efficient potassium transporter providing yeast cells with high lithium tolerance. FEMS Yeast Res 15:fov029

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Acknowledgements

This work was supported by Grant Nos. XX and XXII Plan Propio Investigación, University of Córdoba (JR) and by Grant No. 16-03398S from the Czech Science Foundation (HS).

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Correspondence to José Ramos.

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Caro, G., Bieber, J., Ruiz-Castilla, F.J. et al. Trk1, the sole potassium-specific transporter in Candida glabrata, contributes to the proper functioning of various cell processes. World J Microbiol Biotechnol 35, 124 (2019). https://doi.org/10.1007/s11274-019-2698-6

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Keywords

  • Candida glabrata
  • Potassium transport
  • Trk1
  • Salt tolerance
  • Saccharomyces cerevisiae
  • Membrane potential