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AZR1  -  Azr1p

Saccharomyces cerevisiae S288c

Synonyms: Azole resistance protein 1, G8537, YGR224W
 
 
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Disease relevance of AZR1

 

High impact information on AZR1

  • The S484A enzyme retained half the wild type ATPase activity without affecting azole resistance, but the S307A enzyme was unstable to plasma membrane isolation [2].
  • The changes also reduced the affinity of the enzyme for the azole antifungals ketoconazole and fluconazole and after expression induced by galactose caused 4-5-fold azole resistance in transformants of S. cerevisiae [3].
  • Reintroduction of wild-type or F15 PDR1 fully reversed these effects; together these results demonstrate a role for this gene in both acquired and intrinsic azole resistance [4].
  • In C. glabrata clinical isolates, the predominant mechanism behind azole resistance is upregulated expression of multidrug transporter genes CDR1 and PDH1 [4].
  • These azole resistance-associated changes could affect C. glabrata tissue-specific virulence; in support of this, we detected differences in F15 oxidant, alcohol and weak acid sensitivities [4].
 

Biological context of AZR1

  • These conclusions were based on the higher susceptibility to these compounds of an azr1Delta deletion mutant strain compared with the wild-type and on the increased resistance of both azr1Delta and wild-type strains upon increased expression of the AZR1 gene from a centromeric plasmid clone [5].
  • AZR1 gene expression reduces the duration of acetic acid-induced latency, although the growth kinetics of adapted cells under acetic acid stress is apparently independent of AZR1 expression level [5].
  • We show that the acetate sensitivity phenotype previously ascribed to yeast mutants lacking the Pdr12p and Azr1p plasma membrane transporters is an artefact arising from the use of trp1 mutant strains [6].
  • To identify additional putative azole resistance genes in C. albicans, a genomic library from this organism was screened for complementation of fluconazole hypersusceptibility in Saccharomyces cerevisiae YKKB-13 lacking the ABC (ATP-binding cassette) transporter gene PDR5 [7].
  • A correlation between upregulation of this gene and azole resistance was thus established [8].
 

Anatomical context of AZR1

  • 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 [5].
  • On univariate analysis, more than five episodes of oral candidosis in the last year (P = 0.01), previous use of azole therapy (P = 0.001), C2-3 category of HIV infection (P = 0.01) and low number of circulating CD4+ T-cells (P = 0.03) were significantly associated with an increased risk for the development of azole resistance [9].
  • These findings are in agreement with recent reports of increased azole resistance in Candida species in general and suggest the possibility that the oral cavity may act as a reservoir of resistant yeast isolates in systemic infections [10].
 

Associations of AZR1 with chemical compounds

 

Other interactions of AZR1

 

Analytical, diagnostic and therapeutic context of AZR1

References

  1. Correlation of in vitro fluconazole resistance of Candida isolates in relation to therapy and symptoms of individuals seropositive for human immunodeficiency virus type 1. Cameron, M.L., Schell, W.A., Bruch, S., Bartlett, J.A., Waskin, H.A., Perfect, J.R. Antimicrob. Agents Chemother. (1993) [Pubmed]
  2. Phosphorylation of candida glabrata ATP-binding cassette transporter Cdr1p regulates drug efflux activity and ATPase stability. Wada, S., Tanabe, K., Yamazaki, A., Niimi, M., Uehara, Y., Niimi, K., Lamping, E., Cannon, R.D., Monk, B.C. J. Biol. Chem. (2005) [Pubmed]
  3. The mutation T315A in Candida albicans sterol 14alpha-demethylase causes reduced enzyme activity and fluconazole resistance through reduced affinity. Lamb, D.C., Kelly, D.E., Schunck, W.H., Shyadehi, A.Z., Akhtar, M., Lowe, D.J., Baldwin, B.C., Kelly, S.L. J. Biol. Chem. (1997) [Pubmed]
  4. Pdr1 regulates multidrug resistance in Candida glabrata: gene disruption and genome-wide expression studies. Vermitsky, J.P., Earhart, K.D., Smith, W.L., Homayouni, R., Edlind, T.D., Rogers, P.D. Mol. Microbiol. (2006) [Pubmed]
  5. 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. Tenreiro, S., Rosa, P.C., Viegas, C.A., Sá-Correia, I. Yeast (2000) [Pubmed]
  6. Weak organic acid stress inhibits aromatic amino acid uptake by yeast, causing a strong influence of amino acid auxotrophies on the phenotypes of membrane transporter mutants. Bauer, B.E., Rossington, D., Mollapour, M., Mamnun, Y., Kuchler, K., Piper, P.W. Eur. J. Biochem. (2003) [Pubmed]
  7. A novel multidrug efflux transporter gene of the major facilitator superfamily from Candida albicans (FLU1) conferring resistance to fluconazole. Calabrese, D., Bille, J., Sanglard, D. Microbiology (Reading, Engl.) (2000) [Pubmed]
  8. The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents. Sanglard, D., Ischer, F., Calabrese, D., Majcherczyk, P.A., Bille, J. Antimicrob. Agents Chemother. (1999) [Pubmed]
  9. Analysis of the risk factors associated with the emergence of azole resistant oral candidosis in the course of HIV infection. Tumbarello, M., Caldarola, G., Tacconelli, E., Morace, G., Posteraro, B., Cauda, R., Ortona, L. J. Antimicrob. Chemother. (1996) [Pubmed]
  10. In vitro susceptibility of Candida albicans isolates from apical and marginal periodontitis to common antifungal agents. Waltimo, T.M., Ørstavik, D., Meurman, J.H., Samaranayake, L.P., Haapasalo, M.P. Oral Microbiol. Immunol. (2000) [Pubmed]
  11. Replacement of Candida albicans with C. dubliniensis in human immunodeficiency virus-infected patients with oropharyngeal candidiasis treated with fluconazole. Martinez, M., López-Ribot, J.L., Kirkpatrick, W.R., Coco, B.J., Bachmann, S.P., Patterson, T.F. J. Clin. Microbiol. (2002) [Pubmed]
  12. Candida albicans zinc cluster protein Upc2p confers resistance to antifungal drugs and is an activator of ergosterol biosynthetic genes. MacPherson, S., Akache, B., Weber, S., De Deken, X., Raymond, M., Turcotte, B. Antimicrob. Agents Chemother. (2005) [Pubmed]
  13. Defective sterol C5-6 desaturation and azole resistance: a new hypothesis for the mode of action of azole antifungals. Watson, P.F., Rose, M.E., Ellis, S.W., England, H., Kelly, S.L. Biochem. Biophys. Res. Commun. (1989) [Pubmed]
  14. Multiple amino acid substitutions in lanosterol 14alpha-demethylase contribute to azole resistance in Candida albicans. Favre, B., Didmon, M., Ryder, N.S. Microbiology (Reading, Engl.) (1999) [Pubmed]
  15. Regulation of azole drug susceptibility by Candida albicans protein kinase CK2. Bruno, V.M., Mitchell, A.P. Mol. Microbiol. (2005) [Pubmed]
  16. Overexpression of Erg11p by the regulatable GAL1 promoter confers fluconazole resistance in Saccharomyces cerevisiae. Kontoyiannis, D.P., Sagar, N., Hirschi, K.D. Antimicrob. Agents Chemother. (1999) [Pubmed]
  17. Genetic analysis of azole resistance in the Darlington strain of Candida albicans. Kakeya, H., Miyazaki, Y., Miyazaki, H., Nyswaner, K., Grimberg, B., Bennett, J.E. Antimicrob. Agents Chemother. (2000) [Pubmed]
  18. PDR16-mediated azole resistance in Candida albicans. Saidane, S., Weber, S., De Deken, X., St-Germain, G., Raymond, M. Mol. Microbiol. (2006) [Pubmed]
  19. Surface-active fungicidal D-peptide inhibitors of the plasma membrane proton pump that block azole resistance. Monk, B.C., Niimi, K., Lin, S., Knight, A., Kardos, T.B., Cannon, R.D., Parshot, R., King, A., Lun, D., Harding, D.R. Antimicrob. Agents Chemother. (2005) [Pubmed]
  20. Resistance amongst yeasts isolated from the oral cavities of patients with advanced cancer. Davies, A., Brailsford, S., Broadley, K., Beighton, D. Palliative medicine. (2002) [Pubmed]
 
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