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. 1995 Nov;63(11):4515–4518. doi: 10.1128/iai.63.11.4515-4518.1995

Reduced virulence of Candida albicans mutants affected in multidrug resistance.

J M Becker 1, L K Henry 1, W Jiang 1, Y Koltin 1
PMCID: PMC173643  PMID: 7591094

Abstract

Disruption of a multidrug resistance gene (CaMDR1) in Candida albicans resulted in mutant strains that colonized mouse kidneys to very high levels but were markedly reduced in their virulence. No obvious differences in several properties related to colonization and dissemination were noted among MDR+ or mdr- strains. These results suggest that specific fungal efflux pumps play a role in fungal pathogenicity.

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Selected References

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  1. Balzi E., Goffeau A. Genetics and biochemistry of yeast multidrug resistance. Biochim Biophys Acta. 1994 Aug 30;1187(2):152–162. doi: 10.1016/0005-2728(94)90102-3. [DOI] [PubMed] [Google Scholar]
  2. Balzi E., Wang M., Leterme S., Van Dyck L., Goffeau A. PDR5, a novel yeast multidrug resistance conferring transporter controlled by the transcription regulator PDR1. J Biol Chem. 1994 Jan 21;269(3):2206–2214. [PubMed] [Google Scholar]
  3. Ben-Yaacov R., Knoller S., Caldwell G. A., Becker J. M., Koltin Y. Candida albicans gene encoding resistance to benomyl and methotrexate is a multidrug resistance gene. Antimicrob Agents Chemother. 1994 Apr;38(4):648–652. doi: 10.1128/aac.38.4.648. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boeke J. D., LaCroute F., Fink G. R. A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Mol Gen Genet. 1984;197(2):345–346. doi: 10.1007/BF00330984. [DOI] [PubMed] [Google Scholar]
  5. Doige C. A., Ames G. F. ATP-dependent transport systems in bacteria and humans: relevance to cystic fibrosis and multidrug resistance. Annu Rev Microbiol. 1993;47:291–319. doi: 10.1146/annurev.mi.47.100193.001451. [DOI] [PubMed] [Google Scholar]
  6. Fidel P. L., Jr, Sobel J. D. The role of cell-mediated immunity in candidiasis. Trends Microbiol. 1994 Jun;2(6):202–206. doi: 10.1016/0966-842x(94)90112-i. [DOI] [PubMed] [Google Scholar]
  7. Fling M. E., Kopf J., Tamarkin A., Gorman J. A., Smith H. A., Koltin Y. Analysis of a Candida albicans gene that encodes a novel mechanism for resistance to benomyl and methotrexate. Mol Gen Genet. 1991 Jun;227(2):318–329. doi: 10.1007/BF00259685. [DOI] [PubMed] [Google Scholar]
  8. Fonzi W. A., Irwin M. Y. Isogenic strain construction and gene mapping in Candida albicans. Genetics. 1993 Jul;134(3):717–728. doi: 10.1093/genetics/134.3.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Goffeau A., Slonimski P., Nakai K., Risler J. L. How many yeast genes code for membrane-spanning proteins? Yeast. 1993 Jul;9(7):691–702. doi: 10.1002/yea.320090703. [DOI] [PubMed] [Google Scholar]
  10. Goldway M., Teff D., Schmidt R., Oppenheim A. B., Koltin Y. Multidrug resistance in Candida albicans: disruption of the BENr gene. Antimicrob Agents Chemother. 1995 Feb;39(2):422–426. doi: 10.1128/aac.39.2.422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gottesman M. M., Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem. 1993;62:385–427. doi: 10.1146/annurev.bi.62.070193.002125. [DOI] [PubMed] [Google Scholar]
  12. Gömpel-Klein P., Brendel M. Allelism of SNQ1 and ATR1, genes of the yeast Saccharomyces cerevisiae required for controlling sensitivity to 4-nitroquinoline-N-oxide and aminotriazole. Curr Genet. 1990 Jul;18(1):93–96. doi: 10.1007/BF00321122. [DOI] [PubMed] [Google Scholar]
  13. Higgins C. F. ABC transporters: from microorganisms to man. Annu Rev Cell Biol. 1992;8:67–113. doi: 10.1146/annurev.cb.08.110192.000435. [DOI] [PubMed] [Google Scholar]
  14. Higgins C. F. Flip-flop: the transmembrane translocation of lipids. Cell. 1994 Nov 4;79(3):393–395. doi: 10.1016/0092-8674(94)90248-8. [DOI] [PubMed] [Google Scholar]
  15. Kanazawa S., Driscoll M., Struhl K. ATR1, a Saccharomyces cerevisiae gene encoding a transmembrane protein required for aminotriazole resistance. Mol Cell Biol. 1988 Feb;8(2):664–673. doi: 10.1128/mcb.8.2.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kirsch D. R., Whitney R. R. Pathogenicity of Candida albicans auxotrophic mutants in experimental infections. Infect Immun. 1991 Sep;59(9):3297–3300. doi: 10.1128/iai.59.9.3297-3300.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kuchler K., Thorner J. Functional expression of human mdr1 in the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2302–2306. doi: 10.1073/pnas.89.6.2302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Marger M. D., Saier M. H., Jr A major superfamily of transmembrane facilitators that catalyse uniport, symport and antiport. Trends Biochem Sci. 1993 Jan;18(1):13–20. doi: 10.1016/0968-0004(93)90081-w. [DOI] [PubMed] [Google Scholar]
  19. Odds F. C. Resistance of yeasts to azole-derivative antifungals. J Antimicrob Chemother. 1993 Apr;31(4):463–471. doi: 10.1093/jac/31.4.463. [DOI] [PubMed] [Google Scholar]
  20. Raderer M., Scheithauer W. Clinical trials of agents that reverse multidrug resistance. A literature review. Cancer. 1993 Dec 15;72(12):3553–3563. doi: 10.1002/1097-0142(19931215)72:12<3553::aid-cncr2820721203>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
  21. Raymond M., Gros P., Whiteway M., Thomas D. Y. Functional complementation of yeast ste6 by a mammalian multidrug resistance mdr gene. Science. 1992 Apr 10;256(5054):232–234. doi: 10.1126/science.1348873. [DOI] [PubMed] [Google Scholar]
  22. Ruetz S., Gros P. Phosphatidylcholine translocase: a physiological role for the mdr2 gene. Cell. 1994 Jul 1;77(7):1071–1081. doi: 10.1016/0092-8674(94)90446-4. [DOI] [PubMed] [Google Scholar]
  23. Ruetz S., Raymond M., Gros P. Functional expression of P-glycoprotein encoded by the mouse mdr3 gene in yeast cells. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11588–11592. doi: 10.1073/pnas.90.24.11588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schinkel A. H., Smit J. J., van Tellingen O., Beijnen J. H., Wagenaar E., van Deemter L., Mol C. A., van der Valk M. A., Robanus-Maandag E. C., te Riele H. P. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell. 1994 May 20;77(4):491–502. doi: 10.1016/0092-8674(94)90212-7. [DOI] [PubMed] [Google Scholar]
  25. Sternberg S. The emerging fungal threat. Science. 1994 Dec 9;266(5191):1632–1634. doi: 10.1126/science.7702654. [DOI] [PubMed] [Google Scholar]

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