ABCMdb

ABCB1 p.Arg467Lys

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Publications

PMID: 10546486 [PubMed] Franz R et al: "Molecular aspects of fluconazole resistance development in Candida albicans."

No. Sentence Comment

137 Microbiology 143, 17 White, T. C. (1997) The presence of an R467K amino405-416. Login to comment

PMID: 14688046 [PubMed] Lee MK et al: "Drug resistance genes and trailing growth in Candida albicans isolates."

No. Sentence Comment

220 Five of these, K143R, V404I, F449V, R467K and V509M, were found exclusively in non-trailing isolates with reduced fluconazole susceptibilities (isolates 8-12), andall were due tohomozygous nucleotide substitutions. Login to comment
265 1 2 3 4 5 6 7 8 9 10 11 12 Amino acid substitutiona Reference nucleotideb Nucleotide substitutionc F 105 F T T/C C T/C C T/C T/C D 116 E T T/A A T/A T/A T/A K 119 K A A/G G A/G A/G A/G K 128 T A A/C A/C S 137 S C C/T T C/T T T C/T C/T C/T K 143 R A G H 183 H T T/C C C C L 220 L C C/T T T T T C/T T T E 266 D A C A/C C L 320 L G A V 332 V T T/C C C C C L 340 L A A/G G A/G A/G G K 342 K A A/G G S 361 S A G G L 370 L C C/T T T T T T C/T T T T F 380 F T C C Y 401 Y T C C C C C V 404 I G A P 419 P T C C D 428 D T C C V 437 I G A A G 448 G G G/T A F 449 V T G V 452 V T C V 456 V T A R 467 K G A L 480 L A A/G G G G G G A/G G G N 490 N T T/C C C C C T/C C C V 509 M G A T229A, S279F, K287R, G307S, S405F, G448E, G448R, F449L, V452A, G464S, G465S, R467K and I471T.13,16,17,24 In this study, we found two of these mutations (K143R and R467K) in fluconazole-resistant C. albicans isolates derived from cases of oropharyngeal candidiasis (isolates 11 and 12). Login to comment

PMID: 16251302 [PubMed] Vandeputte P et al: "Mechanisms of azole resistance in a clinical isolate of Candida tropicalis."

No. Sentence Comment

230 At least 12 have been reported to occur in azole-resistant clinical isolates of C. albicans and 7 in C. glabrata, and the mutations most frequently associated with azole resistance were Y132H, D278E, S405F, G464S, and R467K. Login to comment

PMID: 18577180 [PubMed] Dunkel N et al: "Mutations in the multi-drug resistance regulator MRR1, followed by loss of heterozygosity, are the main cause of MDR1 overexpression in fluconazole-resistant Candida albicans strains."

No. Sentence Comment

186 It was previously shown that DSY292 has acquired a Y132H mutation in one ERG11 allele, in addition to the G464S and R467K mutations that were already present in both ERG11 alleles of the matched isolate DSY291 (Sanglard et al., 1998). Login to comment

PMID: 20515567 [PubMed] Chen LM et al: "Overexpression of CDR1 and CDR2 genes plays an important role in fluconazole resistance in Candida albicans with G487T and T916C mutations."

No. Sentence Comment

62 The Erg11p Y132H, T315A, S405F, G464S, R467K and I471T mutations have all been shown to be associated with azole resistance.22 - 25 Some researchers have demonstrated the structural importance of the Y118 amino acid residue in maintaining C. albicans cytochrome P450 14α-sterol demethylase P450 (CACYP51) activity and determining azole susceptibility.26 The contributions of other mutations such as Y79C, D81G, F126L and V130I to fluconazole resistance are still uncertain. Login to comment
141 25 Lamb DC, Kelly DE, White TC, et al: The R467K amino acid substitution in Candida albicans sterol 14α-demethylase causes drug resistance through reduced affinity. Login to comment

PMID: 21282443 [PubMed] Lignell A et al: "Voriconazole-induced inhibition of the fungicidal activity of amphotericin B in Candida strains with reduced susceptibility to voriconazole: an effect not predicted by the MIC value alone."

No. Sentence Comment

83 Summary of drug MICs and mechanisms of resistance to voriconazole for the Candida strains Candida species and strain Name in this study MIC (mg/liter) of: Voriconazole resistance mechanisms Voriconazole Amphotericin B C. albicans C26 CA1MIC8 8 0.5 Increase in CDR1 and CDR2 mRNAs; mutations of ERG11: S405F and Y132H (26) C. albicans C40 CA2MIC8 8 0.5 Increase in MDR1 mRNA; mutations of ERG11: G464S, R467K, and Y132H (26) C. albicans C56 CA3MIC2 2 0.5 Increase in CDR1 and CDR2 mRNAs; mutations of ERG11: G129A and G464S (26) C. albicans 20288.030 CA4MIC256 256 0.5 Increase in CDR1 mRNA; upregulation of ERG11 C. glabrata B346 4018 CG1MIC0.5 0.5 0.5 NAa C. glabrata 263 SMI CG2MIC4 4 0.5 NA C. krusei B336 4026 CK1MIC0.5 0.5 0.5-1 NA C. krusei 20550.054 CK2MIC4 4 0.5 NA C. albicans CCUG 32723 CA5MIC0.004 0.004 0.25 None (voriconazole-susceptible strain included as a quality control) a NA, not analyzed. Login to comment

PMID: 9835492 [PubMed] Franz R et al: "Multiple molecular mechanisms contribute to a stepwise development of fluconazole resistance in clinical Candida albicans strains."

No. Sentence Comment

198 In that case, an R467K amino acid substitution was found in both ERG11 alleles from the isolate with elevated resistance which was not present in the previous isolates and must therefore have occurred in an intermediate isolate not recovered from the patient. Login to comment
200 The G464S mutation, which is located in the heme binding domain of the Erg11p protein near the R467K substitution described by White (38), must have been introduced into one ERG11 allele before conversion to homozygosity. Login to comment

PMID: 12084466 [PubMed] Morschhauser J et al: "The genetic basis of fluconazole resistance development in Candida albicans."

No. Sentence Comment

55 An R467K mutation was detected in both ERG11 alleles of a fluconazole-resistant C. albicans isolate as compared with matched isolates from the same patient with higher sensitivity [20]. Login to comment
61 The amino acid exchanges G129A, Y132H, S405F, G464S and R467K were shown to cause fluconazole resistance by this approach [22]. Login to comment
65 The affinity for fluconazole of 14DM containing the mutations Y132H, G464S or R467K was reduced as compared with the wild-type enzyme, confirming that these naturally occurring mutations indeed caused drug resistance in clinical C. albicans isolates [25-27]. Login to comment
71 Such a change was found for clinical isolates with the G464S or the R467K mutations [20,21]. Login to comment
72 Genetic evidence suggests that a cell with two copies of R467K is significantly more resistant than a cell in which only one allele has the mutation [4]. Login to comment
75 Table 1 provides a list of Table 1 ERG11 mutations causing fluconazole resistance in clinical C. albicans strains Mutation Evidence for contribution to fluconazole resistance Reference A B C D F126L + [24] G129A + + a [22] T229A + + [24] Y132H + + + [22,23,25] G307S + + [24] S405F + + [22] F449S + [24] G464S + + + + [21,22,24,26] R467K + + + + [20,22,27] I471T + [23] A: Mutation found in a fluconazole-resistant isolate but not in a matched susceptible isolate from the same patient. Login to comment
121 For example, White [30] described gradual increases in fluconazole resistance in serial isolates of a C. albicans strain by overexpression of MDR1, ERG11, and one or more of the CDR genes, combined with the aquisition of the R467K mutation in ERG11. Login to comment

PMID: 10579098 [PubMed] Fung-Tomc JC et al: "In vitro antifungal activity of BMS-207147 and itraconazole against yeast strains that are non-susceptible to fluconazole."

No. Sentence Comment

39 ERG11 mRNA levels increased four- to five-fold starting at isolate 13, and a single amino acid substitution (R467K) occurred in ERG11 at isolate 13 (White 1997b). Login to comment
37 ERG11 mRNA levels increased four- to fivefold starting at isolate 13, and a single amino acid substitution (R467K) occurred in ERG11 at isolate 13 (White 1997b). Login to comment

PMID: 16110776 [PubMed] Akins RA et al: "An update on antifungal targets and mechanisms of resistance in Candida albicans."

No. Sentence Comment

40 Strong evidence for another four mutants was provided by showing reduced susceptibilities of demethylase activity from clinical resistant Table 1 Mutations in ERG11 that confer FLZ resistance, and their methods of determination Mutation Effect Method(s) Ref Y132H(F) Altered FLZ binding, no reduction in activity; resistant transformants SDM, confers SDD, confers R in combination with S405F; SDM-EA;/Ca(Sc) confers R growth in combination with G450E; combinations may confer R to posaconazole [11,284,285] T315A Altered FLZ binding, altered heme binding, reduced activity; resistant transformants SDM confers R; SDM-EA [286] R467K Altered heme, reduced FLZ binding; resistant transformants SDM confers SDD; confers R in combination with G464S; SDM-EA [18,287,288] G464S Altered heme, reduced FLZ binding, reduced activity; resistant transformants SDM-EA; /Ca(Sc) confers SDD, confers increased SDD in combination with G129A (a susceptible polymorphism), confers R in combination with R467K, may confer R to posaconazole in combination with G307S [18,289/291] A61V Resistant clinical strain with other mutations, resistant transformants /Ca(Sc) confers SDD growth [291] K143E/ T229A Found together in resistant isolates, resistant enzyme, resistant transformants /Ca(Sc) confers SDD growth; EA [12,291,292] S405F Found in resistant isolates, unique mutation in some, also found in sensitive isolates in combination with other mutations, resistant transformants /Ca(Sc) confers SDD; confers R in combination with Y132H [12,18] G450E Found with other mutations in many resistant strains, resistant enzyme; resistant transformants /Ca(Sc) confers R growth in combination with Y132H; EA [12,291,292] F72L Found in one resistant strain with other mutations, resistant enzyme EA [292] F126L Found in one strain with other mutations, resistant enzyme EA [292] E266D Found with other mutations in many resistant strains, resistant enzyme EA [12,292] F449L Found in strains with other mutations, resistant enzyme EA [12,292] F105L Found in resistant isolates, unique ERG11 mutation in some Correlative, located in substrate access channel in model [12,290] Abbreviations: SDD/susceptible, dose-dependent (resistant in vitro to 8/32 mg/ml FLZ); R: resistant in vitro to 64/mg/ml FLZ). Login to comment

PMID: 25491448 [PubMed] Fuentes M et al: "[Characterization of azole resistance mechanisms in Chilean clinical isolates of Candida albicans]."

No. Sentence Comment

24 Anivel molecular, diversos mecanismos de resistencia a azoles han sido descritos en C. albicans, como mutaciones puntuales en la regi&#f3;n 405-488 del gen que codifica para la enzima "blanco" del f&#e1;rmaco ERG11, como por ejemplo G464S, R467K y I471T, y/o sobre-expresi&#f3;n de este gen21-23 . Login to comment