MFS multidrug transporters in pathogenic fungi: Do they have real clinical impact?

Frontiers in Physiology

Volumn 5 MAY, Issue , 2014, Pages

  Costa, Catarina ^a   Dias, Paulo J ^a   Sá Correia, Isabel ^a   Teixeira, Miguel C ^a  

^a INSTITUTO SUPERIOR TÉCNICO   (Portugal)

Author keywords

Antifungal drug resistance; Candida species; Multidrug resistance efflux pumps; Pathogenic fungi

Indexed keywords

ABC TRANSPORTER; CASPOFUNGIN; DRUG PROTON ION ANTIPORTER; DRUG PROTON ION ANTIPORTER 1; DRUG PROTON ION ANTIPORTER 2; FLUCONAZOLE; ITRACONAZOLE; KETOCONAZOLE; MAJOR FACILITATOR TRANSPORTER PROTEIN; MULTIDRUG RESISTANCE PROTEIN; MULTIDRUG RESISTANCE PROTEIN 1; UNCLASSIFIED DRUG;

ANTIFUNGAL RESISTANCE; ASPERGILLUS FUMIGATUS; CANDIDA ALBICANS; CANDIDA GLABRATA; CANDIDA PARAPSILOSIS; CANDIDA TROPICALIS; CANDIDIASIS; CLAVISPORA LUSITANIAE; CRYPTOCOCCUS NEOFORMANS; DHA1 GENE; DHA2 GENE; FUNGAL GENOME; FUNGAL VIRULENCE; GENE CLUSTER; GENE SEQUENCE; HOST PATHOGEN INTERACTION; HUMAN; MULTIDRUG RESISTANCE; NONHUMAN; OPEN READING FRAME; PHYLOGENETIC TREE; PICHIA GUILLIERMONDII; SACCHAROMYCES CEREVISIAE; SHORT SURVEY;

EID: 84904306087     PISSN: None     EISSN: 1664042X     Source Type: Journal    
DOI: 10.3389/fphys.2014.00197     Document Type: Short Survey

References (47)

1. Albertsen, M., Bellahn, I., Kramer, R., and Waffenschmidt, S. (2003). Localization and function of the yeast multidrug transporter Tpo1p. J. Biol. Chem. 278, 12820-12825. doi: 10.1074/jbc.M210715200.
2. Barchiesi, F., Calabrese, D., Sanglard, D., Falconi Di Francesco, L., Caselli, F., Giannini, D., et al. (2000). Experimental induction of fluconazole resistance in Candida tropicalis ATCC 750. Antimicrob. Agents Chemother. 44, 1578-1584. doi: 10.1128/AAC.44.6.1578-1584.2000.
3. Barker, K. S., Pearson, M. M., and Rogers, P. D. (2003). Identification of genes differentially expressed in association with reduced azole susceptibility in Saccharomyces cerevisiae. J. Antimicrob. Chemother. 51, 1131-1140. doi: 10.1093/jac/dkg217.
4. Bowyer, P., Mosquera, J., Anderson, M., Birch, M., Bromley, M., and Denning, D. W. (2012). Identification of novel genes conferring altered azole susceptibility in Aspergillus fumigatus. FEMS Microbiol. Lett. 332, 10-19. doi: 10.1111/j.1574-6968.2012.02575.x.
5. Brôco, N., Tenreiro, S., Viegas, C. A., and Sá-Correia, I. (1999). FLR1 gene (ORF YBR008c) is required for benomyl and methotrexate resistance in Saccharomyces cerevisiae and its benomyl-induced expression is dependent on Pdr3 transcriptional regulator. Yeast 15, 1595-1608. doi: 10.1002/(SICI)1097-0061(199911)15:15<1595::AID-YEA484>3.0.CO;2-6.
6. Calabrese, D., Bille, J., and Sanglard, D. (2000). A novel multidrug efflux transporter gene of the major facilitator superfamily from Candida albicans (FLU1) conferring resistance to fluconazole. Microbiology 146(Pt 11), 2743-2754.
7. Cannon, R. D., Lamping, E., Holmes, A. R., Niimi, K., Baret, P. V., Keniya, M. V., et al. (2009). Efflux-mediated antifungal drug resistance. Clin. Microbiol. Rev. 22, 291-321. doi: 10.1128/CMR.00051-08.
8. Chaudry, A. N., Travers, P. J., Yuenger, J., Colletta, L., Evans, P., Zenilman, J. M., et al. (2004). Analysis of vaginal acetic acid in patients undergoing treatment for bacterial vaginosis. J. Clin. Microbiol. 42, 5170-5175. doi: 10.1128/JCM.42.11.5170-5175.2004.
9. Chen, K. H., Miyazaki, T., Tsai, H. F., and Bennett, J. E. (2007). The bZip transcription factor Cgap1p is involved in multidrug resistance and required for activation of multidrug transporter gene CgFLR1 in Candida glabrata. Gene 386, 63-72. doi: 10.1016/j.gene.2006.08.010.
10. Costa, C., Henriques, A., Pires, C., Nunes, J., Ohno, M., Chibana, H., et al. (2013a). The dual role of Candida glabrata drug:H+ antiporter CgAqr1 (ORF CAGL0J09944g) in antifungal drug and acetic acid resistance. Front. Microbiol. 4:170. doi: 10.3389/fmicb.2013.00170.
11. Costa, C., Nunes, J., Henriques, A., Mira, N. P., Nakayama, H., Chibana, H., et al. (2014). Candida glabrata drug:H+ antiporter CgTpo3 (ORF CAGL0I10384g): role in azole drug resistance and polyamine homeostasis. J. Antimicrob. Chemother. doi: 10.1093/jac/dku1044. [Epub ahead of print].
12. Costa, C., Pires, C., Cabrito, T. R., Renaudin, A., Ohno, M., Chibana, H., et al. (2013b). Candida glabrata Drug:H+ Antiporter CgQdr2 confers imidazole drug resistance, being activated by transcription factor CgPdr1. Antimicrob. Agents Chemother. 57, 3159-3167. doi: 10.1128/AAC.00811-12.
13. Dias, P. J., and Sá-Correia, I. (2013). The drug:H(+) antiporters of family 2 (DHA2), siderophore transporters (ARN) and glutathione:H(+) antiporters (GEX) have a common evolutionary origin in hemiascomycete yeasts. BMC Genomics 14:901. doi: 10.1186/1471-2164-14-901.
14. Dias, P. J., and Sá-Correia, I. (in press). Phylogenetic and syntenic analyses of the 12-spanner drug:H+ antiporter family 1 (DHA1) in pathogenic Candida species: evolution of MDR1 and FLU1 genes. Genomics. (accepted).
15. Dias, P. J., Seret, M. L., Goffeau, A., Sá-Correia, I., and Baret, P. V. (2010). Evolution of the 12-spanner drug:H+ antiporter DHA1 family in hemiascomycetous yeasts. OMICS 14, 701-710. doi: 10.1089/omi.2010.0104.
16. Ernst, R., Kueppers, P., Stindt, J., Kuchler, K., and Schmitt, L. (2010). Multidrug efflux pumps: substrate selection in ATP-binding cassette multidrug efflux pumps-first come, first served? FEBS J. 277, 540-549. doi: 10.1111/j.1742-4658.2009.07485.x.
17. Felder, T., Bogengruber, E., Tenreiro, S., Ellinger, A., Sá-Correia, I., and Briza, P. (2002). Dtrlp, a multidrug resistance transporter of the major facilitator superfamily, plays an essential role in spore wall maturation in Saccharomyces cerevisiae. Eukaryot. Cell 1, 799-810. doi: 10.1128/EC.1.5.799-810.2002.
18. Gautam, P., Shankar, J., Madan, T., Sirdeshmukh, R., Sundaram, C. S., Gade, W. N., et al. (2008). Proteomic and transcriptomic analysis of Aspergillus fumigatus on exposure to amphotericin B. Antimicrob. Agents Chemother. 52, 4220-4227. doi: 10.1128/AAC.01431-07.
19. Goffeau, A., Barrell, B. G., Bussey, H., Davis, R. W., Dujon, B., Feldmann, H., et al. (1996). Life with 6000 genes. Science 274, 546, 563-547. doi: 10.1126/science.274.5287.546.
20. Goldway, M., Teff, D., Schmidt, R., Oppenheim, A. B., and Koltin, Y. (1995). Multidrug resistance in Candida albicans: disruption of the BENr gene. Antimicrob. Agents Chemother. 39, 422-426. doi: 10.1128/AAC.39.2.422.
21. Gupta, V., Kohli, A., Krishnamurthy, S., Puri, N., Aalamgeer, S. A., Panwar, S., et al. (1998). Identification of polymorphic mutant alleles of CaMDR1, a major facilitator of Candida albicans which confers multidrug resistance, and its in vitro transcriptional activation. Curr. Genet. 34, 192-199. doi: 10.1007/s002940050385.
22. Hayashi, K., Schoonbeek, H. J., and De Waard, M. A. (2002). Bcmfs1, a novel major facilitator superfamily transporter from Botrytis cinerea, provides tolerance towards the natural toxic compounds camptothecin and cercosporin and towards fungicides. Appl. Environ. Microbiol. 68, 4996-5004. doi: 10.1128/AEM.68.10.4996-5004.2002.
23. Hiller, D., Sanglard, D., and Morschhauser, J. (2006). Overexpression of the MDR1 gene is sufficient to confer increased resistance to toxic compounds in Candida albicans. Antimicrob. Agents Chemother. 50, 1365-1371. doi: 10.1128/AAC.50.4.1365-1371.2006.
24. Karababa, M., Coste, A. T., Rognon, B., Bille, J., and Sanglard, D. (2004). Comparison of gene expression profiles of Candida albicans azole-resistant clinical isolates and laboratory strains exposed to drugs inducing multidrug transporters. Antimicrob. Agents Chemother. 48, 3064-3079. doi: 10.1128/AAC.48.8.3064-3079.2004.
25. Li, R., Kumar, R., Tati, S., Puri, S., and Edgerton, M. (2013). Candida albicans flu1-mediated efflux of salivary histatin 5 reduces its cytosolic concentration and fungicidal activity. Antimicrob. Agents Chemother. 57, 1832-1839. doi: 10.1128/AAC.02295-12.
26. Liu, T. T., Znaidi, S., Barker, K. S., Xu, L., Homayouni, R., Saidane, S., et al. (2007). Genome-wide expression and location analyses of the Candida albicans Tac1p regulon. Eukaryot. Cell 6, 2122-2138. doi: 10.1128/EC.00327-07.
27. Markovich, S., Yekutiel, A., Shalit, I., Shadkchan, Y., and Osherov, N. (2004). Genomic approach to identification of mutations affecting caspofungin susceptibility in Saccharomyces cerevisiae. Antimicrob. Agents Chemother. 48, 3871-3876. doi: 10.1128/AAC.48.10.3871-3876.2004.
28. Morschhauser, J. (2010). Regulation of multidrug resistance in pathogenic fungi. Fungal Genet. Biol. 47, 94-106. doi: 10.1016/j.fgb.2009.08.002.
29. Nunes, P. A., Tenreiro, S., and Sá-Correia, I. (2001). Resistance and adaptation to quinidine in Saccharomyces cerevisiae: role of QDR1 (YIL120w), encoding a plasma membrane transporter of the major facilitator superfamily required for multidrug resistance. Antimicrob. Agents Chemother. 45, 1528-1534. doi: 10.1128/AAC.45.5.1528-1534.2001.
30. Roohparvar, R., De Waard, M. A., Kema, G. H., and Zwiers, L. H. (2007). MgMfs1, a major facilitator superfamily transporter from the fungal wheat pathogen Mycosphaerella graminicola, is a strong protectant against natural toxic compounds and fungicides. Fungal Genet. Biol. 44, 378-388. doi: 10.1016/j.fgb.2006.09.007.
31. Sá-Correia, I., Santos, S. C., Teixeira, M. C., Cabrito, T. R., and Mira, N. M. (2009). Drug:H+ antiporters in chemical stress response in yeast. Trends Microbiol. 17, 22-31. doi: 10.1016/j.tim.2008.09.007.
32. Sanglard, D., Ischer, F., Monod, M., and Bille, J. (1997). Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene. Microbiology 143 (Pt 2), 405-416. doi: 10.1099/00221287-143-2-405.
33. Sanglard, D., Kuchler, K., Ischer, F., Pagani, J. L., Monod, M., and Bille, J. (1995). Mechanisms of resistance to azole antifungal agents in Candida albicans isolates from AIDS patients involve specific multidrug transporters. Antimicrob. Agents Chemother. 39, 2378-2386. doi: 10.1128/AAC.39.11.2378.
34. Shah, A. H., Singh, A., Dhamgaye, S., Chauhan, N., Vandeputte, P., Suneetha, K. J., et al. (2014). Novel role of a family of major facilitator transporters in biofilm development and virulence of Candida albicans. Biochem. J. 460, 223-235. doi: 10.1042/BJ20140010.
35. Teixeira, M. C., Cabrito, T. R., Hanif, Z. M., Vargas, R. C., Tenreiro, S., and Sá-Correia, I. (2011). Yeast response and tolerance to polyamine toxicity involving the drug:H+ antiporter Qdr3 and the transcription factors Yap1 and Gcn4. Microbiology 157, 945-956. doi: 10.1099/mic.0.043661-0.
36. Teixeira, M. C., Dias, P. J., Monteiro, P. T., Sala, A., Oliveira, A. L., Freitas, A. T., et al. (2010). Refining current knowledge on the yeast FLR1 regulatory network by combined experimental and computational approaches. Mol. Biosyst. 6, 2471-2481. doi: 10.1039/c004881j.
37. Teixeira, M. C., Dias, P. J., Simoes, T., and Sá-Correia, I. (2008). Yeast adaptation to mancozeb involves the up-regulation of FLR1 under the coordinate control of Yap1, Rpn4, Pdr3, and Yrr1. Biochem. Biophys. Res. Commun. 367, 249-255. doi: 10.1016/j.bbrc.2007.12.056.
38. Tenreiro, S., Nunes, P. A., Viegas, C. A., Neves, M. S., Teixeira, M. C., Cabral, M. G., et al. (2002). AQR1 gene (ORF YNL065w) encodes a plasma membrane transporter of the major facilitator superfamily that confers resistance to short-chain monocarboxylic acids and quinidine in Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 292, 741-748. doi: 10.1006/bbrc.2002.6703.
39. Tenreiro, S., Rosa, P. C., Viegas, C. A., and Sá-Correia, I. (2000). Expression of the AZR1 gene (ORF YGR224w), encoding a plasma membrane transporter of the major facilitator superfamily, is required for adaptation to acetic acid and resistance to azoles in Saccharomyces cerevisiae. Yeast 16, 1469-1481. doi: 10.1002/1097-0061(200012)16:16<1469::AID-YEA640>3.0.CO;2-A.
40. Tomitori, H., Kashiwagi, K., Asakawa, T., Kakinuma, Y., Michael, A. J., and Igarashi, K. (2001). Multiple polyamine transport systems on the vacuolar membrane in yeast. Biochem. J. 353, 681-688. doi: 10.1042/0264-6021:3530681.
41. Tyms, A. S. (1989). "Polyamines and the growth of bacteria and viruses," in The Physiology of Polyamines, eds U. Bachrach and Y. M. Heimer (Boca Raton, FL: CRC Press), 3-33.
42. Vargas, R. C., Garcia-Salcedo, R., Tenreiro, S., Teixeira, M. C., Fernandes, A. R., Ramos, J., et al. (2007). Saccharomyces cerevisiae multidrug resistance transporter Qdr2 is implicated in potassium uptake, providing a physiological advantage to quinidine-stressed cells. Eukaryot. Cell 6, 134-142. doi: 10.1128/EC.00290-06.
43. Velasco, I., Tenreiro, S., Calderon, I. L., and Andre, B. (2004). Saccharomyces cerevisiae Aqr1 is an internal-membrane transporter involved in excretion of amino acids. Eukaryot. Cell 3, 1492-1503. doi: 10.1128/EC.3.6.1492-1503.2004.
44. Wirsching, S., Michel, S., Kohler, G., and Morschhauser, J. (2000a). Activation of the multiple drug resistance gene MDR1 in fluconazole-resistant, clinical Candida albicans strains is caused by mutations in a trans-regulatory factor. J. Bacteriol. 182, 400-404. doi: 10.1128/JB.182.2.400-404.2000.
45. Wirsching, S., Michel, S., and Morschhauser, J. (2000b). Targeted gene disruption in Candida albicans wild-type strains: the role of the MDR1 gene in fluconazole resistance of clinical Candida albicans isolates. Mol. Microbiol. 36, 856-865. doi: 10.1046/j.1365-2958.2000.01899.x.
46. Wirsching, S., Moran, G. P., Sullivan, D. J., Coleman, D. C., and Morschhauser, J. (2001). MDR1-mediated drug resistance in Candida dubliniensis. Antimicrob. Agents Chemother. 45, 3416-3421. doi: 10.1128/AAC.45.12.3416-3421.2001.
47. Yamada-Okabe, T., and Yamada-Okabe, H. (2002). Characterization of the CaNAG3, CaNAG4, and CaNAG6 genes of the pathogenic fungus Candida albicans: possible involvement of these genes in the susceptibilities of cytotoxic agents. FEMS Microbiol. Lett. 212, 15-21. doi: 10.1111/j.1574-6968.2002.tb11238.x.