Potassium Uptake Mediated by Trk1 Is Crucial for Candida glabrata Growth and Fitness

. 2016 ; 11 (4) : e0153374. [epub] 20160408

Jazyk angličtina Země Spojené státy americké Médium electronic-ecollection

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid27058598

The maintenance of potassium homeostasis is crucial for all types of cells, including Candida glabrata. Three types of plasma-membrane systems mediating potassium influx with different transport mechanisms have been described in yeasts: the Trk1 uniporter, the Hak cation-proton symporter and the Acu ATPase. The C. glabrata genome contains only one gene encoding putative system for potassium uptake, the Trk1 uniporter. Therefore, its importance in maintaining adequate levels of intracellular potassium appears to be critical for C. glabrata cells. In this study, we first confirmed the potassium-uptake activity of the identified gene's product by heterologous expression in a suitable S. cerevisiae mutant, further we generated a corresponding deletion mutant in C. glabrata and analysed its phenotype in detail. The obtained results show a pleiotropic effect on the cell physiology when CgTRK1 is deleted, affecting not only the ability of trk1Δ to grow at low potassium concentrations, but also the tolerance to toxic alkali-metal cations and cationic drugs, as well as the membrane potential and intracellular pH. Taken together, our results find the sole potassium uptake system in C. glabrata cells to be a promising target in the search for its specific inhibitors and in developing new antifungal drugs.

Zobrazit více v PubMed

Bolotin-Fukuhara M, Fairhead C. Candida glabrata: a deadly companion? Yeast. 2014;31: 279–88. 10.1002/yea.3019 PubMed DOI

Hazen KC. New and emerging yeast pathogens. Clin Microbiol Rev. 1995;8: 462–78. PubMed PMC

Just G, Steinheimer D, Schnellbach M, Böttinger C, Helm EB, Stille W. Change of causative organisms under antifungal treatment in immunosuppressed patients with HIV-infections. Mycoses. 1989;32: 47–51. PubMed

Perlroth J, Choi B, Spellberg B. Nosocomial fungal infections: epidemiology, diagnosis, and treatment. Med Mycol. 2007;45: 321–46. PubMed

Borst A, Raimer MT, Warnock DW, Morrison CJ, Arthington-Skaggs BA. Rapid acquisition of stable azole resistance by Candida glabrata isolates obtained before the clinical introduction of fluconazole. Antimicrob Agents Chemother. 2005;49: 783–7. PubMed PMC

Gabaldón T, Martin T, Marcet-Houben M, Durrens P, Bolotin-Fukuhara M, Lespinet O, et al. Comparative genomics of emerging pathogens in the Candida glabrata clade. BMC Genomics. 2013;14: 623 10.1186/1471-2164-14-623 PubMed DOI PMC

Dujon B, Sherman D, Fischer G, Durrens P, Casaregola S, Lafontaine I, et al. Genome evolution in yeasts. Nature. 2004;430: 35–44. PubMed

Kurtzman CP, Robnett CJ. Identification and phylogeny of ascomycetous yeasts from analysis of nuclear large subunit (26S) ribosomal DNA partial sequences. Antonie Van Leeuwenhoek. 1998;73: 331–71. PubMed

Roetzer A, Gabaldón T, Schüller C. From Saccharomyces cerevisiae to Candida glabrata in a few easy steps: important adaptations for an opportunistic pathogen. FEMS Microbiol Lett. 2011;314: 1–9. 10.1111/j.1574-6968.2010.02102.x PubMed DOI PMC

Vermitsky J-P, Earhart KD, Smith WL, Homayouni R, Edlind TD, Rogers PD. Pdr1 regulates multidrug resistance in Candida glabrata: gene disruption and genome-wide expression studies. Mol Microbiol. 2006;61: 704–22. PubMed

Ramos J, Ariño J, Sychrová H. Alkali-metal-cation influx and efflux systems in nonconventional yeast species. FEMS Microbiol Lett. 2011;317: 1–8. 10.1111/j.1574-6968.2011.02214.x PubMed DOI

Ariño J, Aydar E, Drulhe S, Ganser D, Jorrín J, Kahm M, et al. Systems biology of monovalent cation homeostasis in yeast: the translucent contribution. Adv Microb Physiol. 2014;64: 1–63. 10.1016/B978-0-12-800143-1.00001-4 PubMed DOI

Pohl HR, Wheeler JS, Murray HE. Sodium and potassium in health and disease. Met Ions Life Sci. 2013;13: 29–47. 10.1007/978-94-007-7500-8_2 PubMed DOI

Szczerba MW, Britto DT, Kronzucker HJ. K+ transport in plants: physiology and molecular biology. J Plant Physiol. 2009;166: 447–66. 10.1016/j.jplph.2008.12.009 PubMed DOI

Cyert MS, Philpott CC. Regulation of cation balance in Saccharomyces cerevisiae. Genetics. 2013;193: 677–713. 10.1534/genetics.112.147207 PubMed DOI PMC

Ariño J, Ramos J, Sychrová H. Alkali metal cation transport and homeostasis in yeasts. Microbiol Mol Biol Rev. 2010;74: 95–120. 10.1128/MMBR.00042-09 PubMed DOI PMC

Yenush L, Merchan S, Holmes J, Serrano R. pH-Responsive, posttranslational regulation of the Trk1 potassium transporter by the type 1-related Ppz1 phosphatase. Mol Cell Biol. 2005;25: 8683–92. PubMed PMC

Gelis S, González-Fernández R, Herrera R, Jorrín J, Ramos J. A physiological, biochemical and proteomic characterization of Saccharomyces cerevisiae trk1,2 transport mutants grown under limiting potassium conditions. Microbiology. 2015;161: 1260–70. 10.1099/mic.0.000078 PubMed DOI

Herrera R, Alvarez MC, Gelis S, Kodedová M, Sychrová H, Kschischo M, et al. Role of Saccharomyces cerevisiae Trk1 in stabilization of intracellular potassium content upon changes in external potassium levels. Biochim Biophys Acta. 2014;1838: 127–33. 10.1016/j.bbamem.2013.08.022 PubMed DOI

Kahm M, Navarrete C, Llopis-Torregrosa V, Herrera R, Barreto L, Yenush L, et al. Potassium starvation in yeast: mechanisms of homeostasis revealed by mathematical modeling. PLoS Comput Biol. 2012;8: e1002548 10.1371/journal.pcbi.1002548 PubMed DOI PMC

Barreto L, Canadell D, Petrezsélyová S, Navarrete C, Maresová L, Peréz-Valle J, et al. A genomewide screen for tolerance to cationic drugs reveals genes important for potassium homeostasis in Saccharomyces cerevisiae. Eukaryotic Cell. 2011;10: 1241–50. 10.1128/EC.05029-11 PubMed DOI PMC

Enjalbert B, Moran GP, Vaughan C, Yeomans T, Maccallum DM, Quinn J, et al. Genome-wide gene expression profiling and a forward genetic screen show that differential expression of the sodium ion transporter Ena21 contributes to the differential tolerance of Candida albicans and Candida dubliniensis to osmotic stress. Mol Microbiol. 2009;72: 216–28. 10.1111/j.1365-2958.2009.06640.x PubMed DOI

Kinclová O, Potier S, Sychrová H. The Candida albicans Na+/H+ antiporter exports potassium and rubidium. FEBS Lett. 2001;504: 11–5. PubMed

Krauke Y, Sychrová H. Functional comparison of plasma-membrane Na+/H+ antiporters from two pathogenic Candida species. BMC Microbiol. 2008;8: 80 10.1186/1471-2180-8-80 PubMed DOI PMC

Elicharová H, Sychrová H. Fluconazole affects the alkali-metal-cation homeostasis and susceptibility to cationic toxic compounds of Candida glabrata. Microbiology. 2014;160: 1705–13. 10.1099/mic.0.078600-0 PubMed DOI

Zimmermannová O, Salazar A, Sychrová H, Ramos J. Zygosaccharomyces rouxii Trk1 is an efficient potassium transporter providing yeast cells with high lithium tolerance. FEMS Yeast Res. 2015;15: fov029 10.1093/femsyr/fov029 PubMed DOI

Martínez JL, Sychrová H, Ramos J. Monovalent cations regulate expression and activity of the Hak1 potassium transporter in Debaryomyces hansenii. Fungal Genet Biol. 2011;48: 177–84. 10.1016/j.fgb.2010.06.013 PubMed DOI

Stříbný J, Kinclová-Zimmermannová O, Sychrová H. Potassium supply and homeostasis in the osmotolerant non-conventional yeasts Zygosaccharomyces rouxii differ from Saccharomyces cerevisiae. Curr Genet. 2012;58: 255–64. 10.1007/s00294-012-0381-7 PubMed DOI

Benito B, Garciadeblás B, Schreier P, Rodríguez-Navarro A. Novel p-type ATPases mediate high-affinity potassium or sodium uptake in fungi. Eukaryotic Cell. 2004;3: 359–68. PubMed PMC

Baev D, Rivetta A, Vylkova S, Sun JN, Zeng G-F, Slayman CL, et al. The TRK1 potassium transporter is the critical effector for killing of Candida albicans by the cationic protein, Histatin 5. J Biol Chem. 2004;279: 55060–72. PubMed

Miranda M, Bashi E, Vylkova S, Edgerton M, Slayman C, Rivetta A. Conservation and dispersion of sequence and function in fungal TRK potassium transporters: focus on Candida albicans. FEMS Yeast Res. 2009;9: 278–92. 10.1111/j.1567-1364.2008.00471.x PubMed DOI

Hušeková B, Elicharová H, Sychrová H. Pathogenic Candida species differ in the ability to grow at limiting potassium concentrations. Can J Microbiol. 2015, in press. 10.1139/cjm-2015-0766 PubMed DOI

Reuss O, Vik A, Kolter R, Morschhäuser J. The SAT1 flipper, an optimized tool for gene disruption in Candida albicans. Gene. 2004;341: 119–27. PubMed

Petrezsélyová S, Ramos J, Sychrová H. Trk2 transporter is a relevant player in K+ supply and plasma-membrane potential control in Saccharomyces cerevisiae. Folia Microbiol (Praha). 2011;56: 23–8. PubMed

Hill JE, Myers AM, Koerner TJ, Tzagoloff A. Yeast/E. coli shuttle vectors with multiple unique restriction sites. Yeast. 1986;2: 163–7. PubMed

Myers AM, Tzagoloff A, Kinney DM, Lusty CJ. Yeast shuttle and integrative vectors with multiple cloning sites suitable for construction of lacZ fusions. Gene. 1986;45: 299–310. PubMed

Kinclová O, Ramos J, Potier S, Sychrová H. Functional study of the Saccharomyces cerevisiae Nha1p C-terminus. Mol Microbiol. 2001;40: 656–68. PubMed

Ullah A, Lopes MI, Brul S, Smits GJ. Intracellular pH homeostasis in Candida glabrata in infection-associated conditions. Microbiology. 2013;159: 803–13. 10.1099/mic.0.063610-0 PubMed DOI

Krauke Y, Sychrova H. Cnh1 Na+ /H+ antiporter and Ena1 Na+ -ATPase play different roles in cation homeostasis and cell physiology of Candida glabrata. FEMS Yeast Res. 2011;11: 29–41. 10.1111/j.1567-1364.2010.00686.x PubMed DOI

Camacho M, Ramos J, Rodriguez-Navarro A. Potassium requirements of Saccharomyces cerevisiae. Curr Microbiol 1981;6: 295–9.

Gášková D, Brodská B, Herman P, Večeř J, Malínský J, Sigler K, et al. Fluorescent probing of membrane potential in walled cells: diS-C3(3) assay in Saccharomyces cerevisiae. Yeast. 1998;14: 1189–97. PubMed

Hendrych T, Kodedová M, Sigler K, Gášková D. Characterization of the kinetics and mechanisms of inhibition of drugs interacting with the S. cerevisiae multidrug resistance pumps Pdr5p and Snq2p. Biochim Biophys Acta. 2009;1788: 717–23. 10.1016/j.bbamem.2008.12.001 PubMed DOI

Kodedová M, Sychrová H. 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. 2015;10: e0139306 10.1371/journal.pone.0139306 PubMed DOI PMC

Miesenböck G, De Angelis DA, Rothman JE. Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature. 1998;394: 192–5. PubMed

Marešová L, Hošková B, Urbánková E, Chaloupka R, Sychrová H. New applications of pHluorin-measuring intracellular pH of prototrophic yeasts and determining changes in the buffering capacity of strains with affected potassium homeostasis. Yeast. 2010: 317–25. 10.1002/yea.1755 PubMed DOI

Orij R, Postmus J, Ter Beek A, Brul S, Smits GJ. In vivo measurement of cytosolic and mitochondrial pH using a pH-sensitive GFP derivative in Saccharomyces cerevisiae reveals a relation between intracellular pH and growth. Microbiology. 2009;155: 268–78. 10.1099/mic.0.022038-0 PubMed DOI

Navarrete C, Petrezsélyová S, Barreto L, Martínez JL, Zahrádka J, Ariño J, et al. Lack of main K+ uptake systems in Saccharomyces cerevisiae cells affects yeast performance in both potassium-sufficient and potassium-limiting conditions. FEMS Yeast Res. 2010;10: 508–17. 10.1111/j.1567-1364.2010.00630.x PubMed DOI

Vale-Silva LA, Sanglard D. Tipping the balance both ways: drug resistance and virulence in Candida glabrata. FEMS Yeast Res. 2015;15: fov025 10.1093/femsyr/fov025 PubMed DOI

Ho H, Haynes K. Candida glabrata: new tools and technologies-expanding the toolkit. FEMS Yeast Res. 2015;15. PubMed PMC

Bañuelos MA, Sychrová H, Bleykasten-Grosshans C, Souciet JL, Potier S. The Nha1 antiporter of Saccharomyces cerevisiae mediates sodium and potassium efflux. Microbiology. 1998;144: 2749–58. PubMed

Gómez MJ, Luyten K, Ramos J. The capacity to transport potassium influences sodium tolerance in Saccharomyces cerevisiae. FEMS Microbiol Lett. 1996;135: 157–60. PubMed

Bertl A, Ramos J, Ludwig J, Lichtenberg-Fraté H, Reid J, Bihler H, et al. Characterization of potassium transport in wild-type and isogenic yeast strains carrying all combinations of trk1, trk2 and tok1 null mutations. Mol Microbiol. 2003;47: 767–80. PubMed

Bihler H, Slayman CL, Bertl A. Low-affinity potassium uptake by Saccharomyces cerevisiae is mediated by NSC1, a calcium-blocked non-specific cation channel. Biochim Biophys Acta. 2002;1558: 109–18. PubMed

Najít záznam

Citační ukazatele

Nahrávání dat ...

    Možnosti archivace