ABCMdb

PMID: 12084466

Morschhauser J
The genetic basis of fluconazole resistance development in Candida albicans.
Biochim Biophys Acta. 2002 Jul 18;1587(2-3):240-8., [PubMed]

Sentences

No. Mutations Sentence Comment

55 ABCB1 p.Arg467Lys 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 ABCB1 p.Arg467Lys The amino acid exchanges G129A, Y132H, S405F, G464S and R467K were shown to cause fluconazole resistance by this approach [22]. Login to comment 65 ABCB1 p.Arg467Lys 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 ABCB1 p.Arg467Lys Such a change was found for clinical isolates with the G464S or the R467K mutations [20,21]. Login to comment 72 ABCB1 p.Arg467Lys 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 ABCB1 p.Arg467Lys 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 ABCB1 p.Arg467Lys 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