| Structural highlights
Function
CDR1_CANGA Pleiotropic ABC efflux transporter that transports and confers resistance to structurally and functionally unrelated compounds including rhodamine 6G, Nile red, caspofungin, cycloheximide, or azoles such as fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole, and isavuconazole (PubMed:10543759, PubMed:12244114, PubMed:15105111, PubMed:15105136, PubMed:15388433, PubMed:15498768, PubMed:16803598, PubMed:17581937, PubMed:18591262, PubMed:20038613, PubMed:20450660, PubMed:21134356, PubMed:21408004, PubMed:22788839, PubMed:26482310, PubMed:27486188, PubMed:29371812, PubMed:29784839). Chlorbromuron, itraconazole, yohimbine, ketoconazole, miconazole, clotrimazole, DE-11, tamoxifen, quinidine, verapamil can compete for rhodamine 6G's binding site(s) while compounds such as propanil, chloramphenicol, benomyl, voriconazole, tritylimidazole, ketoconazole, miconazole, tamoxifen, gefitinib shared binding site(s) with fluconazole. Nile red mediated efflux appears to be relatively more specific since only five compounds such as ZW3-12, rhodamine 123, miconazole, clotrimazole, and itraconazole can inhibit its accumulation (PubMed:21134356). Does not use as substrates 4-nitroquinoline 1-oxide (4-NQO) and disulfiram (PubMed:21134356). Does not play a role in the azole resistance in mature biofilms (PubMed:18651314).[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19]
References
- ↑ Sanglard D, Ischer F, Calabrese D, Majcherczyk PA, Bille J. The ATP binding cassette transporter gene CgCDR1 from Candida glabrata is involved in the resistance of clinical isolates to azole antifungal agents. Antimicrob Agents Chemother. 1999 Nov;43(11):2753-65. PMID:10543759 doi:10.1128/AAC.43.11.2753
- ↑ Wada S, Niimi M, Niimi K, Holmes AR, Monk BC, Cannon RD, Uehara Y. Candida glabrata ATP-binding cassette transporters Cdr1p and Pdh1p expressed in a Saccharomyces cerevisiae strain deficient in membrane transporters show phosphorylation-dependent pumping properties. J Biol Chem. 2002 Nov 29;277(48):46809-21. PMID:12244114 doi:10.1074/jbc.M207817200
- ↑ Kaur R, Castaño I, Cormack BP. Functional genomic analysis of fluconazole susceptibility in the pathogenic yeast Candida glabrata: roles of calcium signaling and mitochondria. Antimicrob Agents Chemother. 2004 May;48(5):1600-13. PMID:15105111 doi:10.1128/AAC.48.5.1600-1613.2004
- ↑ Brun S, Bergès T, Poupard P, Vauzelle-Moreau C, Renier G, Chabasse D, Bouchara JP. Mechanisms of azole resistance in petite mutants of Candida glabrata. Antimicrob Agents Chemother. 2004 May;48(5):1788-96. PMID:15105136 doi:10.1128/AAC.48.5.1788-1796.2004
- ↑ Vermitsky JP, Edlind TD. Azole resistance in Candida glabrata: coordinate upregulation of multidrug transporters and evidence for a Pdr1-like transcription factor. Antimicrob Agents Chemother. 2004 Oct;48(10):3773-81. PMID:15388433 doi:10.1128/AAC.48.10.3773-3781.2004
- ↑ Wada S, Tanabe K, Yamazaki A, Niimi M, Uehara Y, Niimi K, Lamping E, Cannon RD, Monk BC. Phosphorylation of candida glabrata ATP-binding cassette transporter Cdr1p regulates drug efflux activity and ATPase stability. The Journal of biological chemistry. 2005 Jan 7. doi: 10.1074/jbc.M408252200. PMID: 15498768.
- ↑ Vermitsky JP, 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 Aug;61(3):704-22. doi: 10.1111/j.1365-2958.2006.05235.x. Epub , 2006 Jun 27. PMID:16803598 doi:https://dx.doi.org/10.1111/j.1365-2958.2006.05235.x
- ↑ Shin JH, Chae MJ, Song JW, Jung SI, Cho D, Kee SJ, Kim SH, Shin MG, Suh SP, Ryang DW. Changes in karyotype and azole susceptibility of sequential bloodstream isolates from patients with Candida glabrata candidemia. J Clin Microbiol. 2007 Aug;45(8):2385-91. doi: 10.1128/JCM.00381-07. Epub 2007 , Jun 20. PMID:17581937 doi:https://dx.doi.org/10.1128/JCM.00381-07
- ↑ Gygax SE, Vermitsky JP, Chadwick SG, Self MJ, Zimmerman JA, Mordechai E, Adelson ME, Trama JP. Antifungal resistance of Candida glabrata vaginal isolates and development of a quantitative reverse transcription-PCR-based azole susceptibility assay. Antimicrob Agents Chemother. 2008 Sep;52(9):3424-6. doi: 10.1128/AAC.00462-08. , Epub 2008 Jun 30. PMID:18591262 doi:https://dx.doi.org/10.1128/AAC.00462-08
- ↑ Song JW, Shin JH, Kee SJ, Kim SH, Shin MG, Suh SP, Ryang DW. Expression of CgCDR1, CgCDR2, and CgERG11 in Candida glabrata biofilms formed by bloodstream isolates. Med Mycol. 2009;47(5):545-8. doi: 10.1080/13693780802210726. PMID:18651314 doi:https://dx.doi.org/10.1080/13693780802210726
- ↑ Chapeland-Leclerc F, Hennequin C, Papon N, Noel T, Girard A, Socie G, Ribaud P, Lacroix C. Acquisition of flucytosine, azole, and caspofungin resistance in Candida glabrata bloodstream isolates serially obtained from a hematopoietic stem cell transplant recipient. Antimicrob Agents Chemother. 2010 Mar;54(3):1360-2. doi: 10.1128/AAC.01138-09. , Epub 2009 Dec 28. PMID:20038613 doi:https://dx.doi.org/10.1128/AAC.01138-09
- ↑ Shen YZ, Lu HZ, Zhang YX. [Molecular mechanisms of fluconazole resistance in clinical isolates of Candida glabrata]. Zhonghua nei ke za zhi. 2010 Mar 1. PMID: 20450660.
- ↑ Puri N, Manoharlal R, Sharma M, Sanglard D, Prasad R. Overcoming the heterologous bias: an in vivo functional analysis of multidrug efflux transporter, CgCdr1p in matched pair clinical isolates of Candida glabrata. Biochem Biophys Res Commun. 2011 Jan 7;404(1):357-63. doi: , 10.1016/j.bbrc.2010.11.123. Epub 2010 Dec 4. PMID:21134356 doi:https://dx.doi.org/10.1016/j.bbrc.2010.11.123
- ↑ Ferrari S, Sanguinetti M, Torelli R, Posteraro B, Sanglard D. Contribution of CgPDR1-regulated genes in enhanced virulence of azole-resistant Candida glabrata. PLoS One. 2011 Mar 9;6(3):e17589. doi: 10.1371/journal.pone.0017589. PMID:21408004 doi:https://dx.doi.org/10.1371/journal.pone.0017589
- ↑ Niimi K, Harding DR, Holmes AR, Lamping E, Niimi M, Tyndall JD, Cannon RD, Monk BC. Specific interactions between the Candida albicans ABC transporter Cdr1p ectodomain and a D-octapeptide derivative inhibitor. Mol Microbiol. 2012 Aug;85(4):747-67. doi: 10.1111/j.1365-2958.2012.08140.x. Epub , 2012 Jul 13. PMID:22788839 doi:https://dx.doi.org/10.1111/j.1365-2958.2012.08140.x
- ↑ Sanglard D, Coste AT. Activity of Isavuconazole and Other Azoles against Candida Clinical Isolates and Yeast Model Systems with Known Azole Resistance Mechanisms. Antimicrob Agents Chemother. 2015 Oct 19;60(1):229-38. doi: 10.1128/AAC.02157-15. , Print 2016 Jan. PMID:26482310 doi:https://dx.doi.org/10.1128/AAC.02157-15
- ↑ Ben-Ami R, Zimmerman O, Finn T, Amit S, Novikov A, Wertheimer N, Lurie-Weinberger M, Berman J. Heteroresistance to Fluconazole Is a Continuously Distributed Phenotype among Candida glabrata Clinical Strains Associated with In Vivo Persistence. mBio. 2016 Aug 2;7(4):e00655-16. doi: 10.1128/mBio.00655-16. PMID:27486188 doi:https://dx.doi.org/10.1128/mBio.00655-16
- ↑ Kim M, Lee H, Hwang SY, Lee I, Jung WH. Azole Resistance Caused by Increased Drug Efflux in Candida glabrata Isolated from the Urinary Tract of a Dog with Diabetes Mellitus. Mycobiology. 2017 Dec;45(4):426-429. doi: 10.5941/MYCO.2017.45.4.426. Epub 2017 , Dec 31. PMID:29371812 doi:https://dx.doi.org/10.5941/MYCO.2017.45.4.426
- ↑ Goemaere B, Lagrou K, Spriet I, Hendrickx M, Becker P. Clonal Spread of Candida glabrata Bloodstream Isolates and Fluconazole Resistance Affected by Prolonged Exposure: a 12-Year Single-Center Study in Belgium. Antimicrob Agents Chemother. 2018 Jul 27;62(8):e00591-18. doi: , 10.1128/AAC.00591-18. Print 2018 Aug. PMID:29784839 doi:https://dx.doi.org/10.1128/AAC.00591-18
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