ABCB1 p.Phe104Val
| Predicted by SNAP2: | A: N (66%), C: N (87%), D: D (53%), E: N (72%), G: N (66%), H: N (72%), I: N (78%), K: N (72%), L: N (87%), M: N (93%), N: N (78%), P: N (61%), Q: N (82%), R: N (66%), S: N (87%), T: N (78%), V: N (87%), W: N (66%), Y: N (87%), |
| Predicted by PROVEAN: | A: N, C: N, D: N, E: N, G: N, H: N, I: N, K: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: N, Y: N, |
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[hide] Deciphering azole resistance mechanisms with a foc... Int J Antimicrob Agents. 2013 Nov;42(5):410-5. doi: 10.1016/j.ijantimicag.2013.07.013. Epub 2013 Aug 29. Morio F, Pagniez F, Besse M, Gay-andrieu F, Miegeville M, Le Pape P
Deciphering azole resistance mechanisms with a focus on transcription factor-encoding genes TAC1, MRR1 and UPC2 in a set of fluconazole-resistant clinical isolates of Candida albicans.
Int J Antimicrob Agents. 2013 Nov;42(5):410-5. doi: 10.1016/j.ijantimicag.2013.07.013. Epub 2013 Aug 29., [PMID:24051054]
Abstract [show]
Several and often combined mechanisms can lead to acquired azole resistance in Candida albicans and subsequent therapeutic failure. The aim of this study was to provide a complete overview of the molecular basis of azole resistance in a set of six C. albicans clinical isolates recovered from patients who failed azole therapy. For this purpose, expression levels of CDR1, MDR1 and ERG11 were investigated by reverse transcription PCR (RT-PCR) together with amplification and sequencing of the genes encoding their transcription factors TAC1, MRR1 and UPC2. In all, the data underline that azole resistance in this set of clinical isolates results from distinct, often combined, mechanisms, being mostly driven by CDR1 and/or MDR1 active efflux. We show that gain-of-function (GOF) mutations in the transcription-factor-encoding genes TAC1, MRR1 and UPC2 are a common event in azole-resistant C. albicans clinical isolates. In addition, together with the finding that these genes are highly permissive to nucleotide changes, we describe several novel mutations that could act as putative GOF mutations involved in fluconazole resistance.
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122 Table 4 Amino acid substitutions in the transcription factors Tac1p, Mrr1p, Upc2p and in Erg11p.a Isolate Amino acid substitutions in Erg11pb Amino acid substitutions in Tac1p Amino acid substitutions in Mrr1pc Amino acid substitutions in Upc2p CAAL28 S405F L47K, F104V, S199N, R206H, V207A, S264P, N396S, D776N, E829Q, N896S, S941P L248Vh ,V341Eh , E1020Q I142Sh , A451Vh CAAL37 E266D, G464S, V456Ih , V488I L47K, S199N, R206H, V207A, D776N, E829Q, E841G, N896S, S941P N937K, E1020Q, F1032L R68Kh , I142Sh , S190Nh , S228Nh CAAL61 G307S, Y447H L47K, K87Nh , M170Ih , N174Dh , F189Sh , S199Nh , R206Hh , V207Ah , A377Vh , N396Sh , N772Kh , D776Nh , E829Qh , S941Ph K884E I142S, G648S CAAL67 G450E L47K, K87Nh , F104Vh , M170Ih , N174Dh , F189Sh , S199N, R206H, V207A, T225Ah , N396S, W442stoph , I558Vh , N772Kh , D776N, E829Q, N896Sh , S941P N937K, E1020Q, F1032L, S1037L I142Sh CAAL74 Y132F, E266D, G448V, V488I L47K, F104Vh , S199Nh , R206Hh , V207Ah , N396Sh , D776Nh , E829Qh , N896Sh , S941Ph S171P, R557K, E1020Q R68Kh , I142S, S228Nh , T273Ah , G648Sh , K684Eh CAAL75 D116E, Y132H, K143R L47K, F104V, S199N, R206H, V207A, N396S, W486C, D776N, E829Q, N896S, S941P, G980Wh S171P, E1020Q R68K h , I142S h , S228N h , T273A h h , heterozygous (mutation in a single allele).
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ABCB1 p.Phe104Val 24051054:122:264
status: NEWX
ABCB1 p.Phe104Val 24051054:122:1102
status: NEW[hide] Mechanisms of azole resistance in Candida albicans... Res Microbiol. 2015 Apr;166(3):153-61. doi: 10.1016/j.resmic.2015.02.009. Epub 2015 Mar 6. Liu JY, Shi C, Wang Y, Li WJ, Zhao Y, Xiang MJ
Mechanisms of azole resistance in Candida albicans clinical isolates from Shanghai, China.
Res Microbiol. 2015 Apr;166(3):153-61. doi: 10.1016/j.resmic.2015.02.009. Epub 2015 Mar 6., [PMID:25748216]
Abstract [show]
This study was undertaken to characterize the mechanism(s) of azole resistance in clinical isolates of Candida albicans collected in Shanghai, China, focusing on the role of efflux pumps, target enzymes of fluconazole (Erg11), respiratory status and the ergosterol biosynthetic pathway. Clinical isolates of C. albicans (n = 30) were collected from 30 different non-HIV-infected patients in four hospitals in Shanghai. All 30 C. albicans isolates were susceptible to amphotericin B and 5-fluorocytosine. Twelve C. albicans isolates showed resistance to at least one type of triazole antifungal. Flow cytometry analysis of rhodamine 6G efflux showed that azole-resistant isolates had greater efflux pump activity, which was consistent with elevated levels of CDR1 and CDR2 genes that code for ABC efflux pumps. However, we did not observe increased expression of ERG11 and MDR1 or respiratory deficiency. Several mutations of ERG11 and TAC1 genes were detected. The F964Y mutation in the TAC1 gene was identified for the first time. Two main sterols, ergosterol and lanosterol, were identified by GC-MS chromatogram, and no missense mutations were found in ERG3. Furthermore, seven amino acid substitutions in ERG11, A114S, Y132H, Y132F, K143Q, K143R, Y257H and G448E were found, by Type II spectral quantitative analysis, to contribute to low affinity binding between Erg11 and fluconazole.
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No. Sentence Comment
158 S199N, F104V and L935S were found in both azole-susceptible and -resistant strains.
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ABCB1 p.Phe104Val 25748216:158:7
status: NEW182 Two other known mutations F104V and S199N and one novel mutation, L935S, were observed in some azole-sensitive isolates from our laboratory, suggesting that these substitutions are not involved in azole resistance.
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ABCB1 p.Phe104Val 25748216:182:26
status: NEW