ABCB1 p.Val125Ala
| Predicted by SNAP2: | A: N (87%), C: N (78%), D: D (71%), E: N (53%), F: D (59%), G: D (53%), H: N (53%), I: N (93%), K: D (59%), L: N (57%), M: N (72%), N: D (53%), P: D (66%), Q: N (61%), R: D (59%), S: N (66%), T: N (66%), W: D (71%), Y: D (63%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: N, K: D, L: N, M: N, N: D, P: D, Q: D, R: D, S: D, T: D, W: D, Y: D, |
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[hide] Molecular mechanisms of fluconazole resistance in ... Antimicrob Agents Chemother. 2002 Jun;46(6):1695-703. Perea S, Lopez-Ribot JL, Wickes BL, Kirkpatrick WR, Dib OP, Bachmann SP, Keller SM, Martinez M, Patterson TF
Molecular mechanisms of fluconazole resistance in Candida dubliniensis isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis.
Antimicrob Agents Chemother. 2002 Jun;46(6):1695-703., [PMID:12019078]
Abstract [show]
Candida dubliniensis is a newly identified species of Candida that is phenotypically similar to but genetically distinct from C. albicans. This organism has been recovered with increasing frequency from the oral cavities of human immunodeficiency virus (HIV)-infected and AIDS patients and has been implicated as a causative agent of oral candidiasis and systemic disease. In the present study we characterized the molecular mechanisms of resistance to fluconazole (FLC) in C. dubliniensis clinical isolates from two different HIV-infected patients with oropharyngeal candidiasis. Isolates were identified to the species level by phenotypic and genotypic tests. DNA-typing techniques were used to assess strain identity. Antifungal susceptibility testing was performed by NCCLS techniques. Northern blotting analysis was used to monitor the expression of genes encoding lanosterol demethylase (ERG11) and efflux transporters (CDR and MDR1) in matched sets of C. dubliniensis-susceptible and -resistant isolates by using probes generated from their homologous C. albicans sequences. In addition, ERG11 genes were amplified by PCR, and their nucleotide sequences were determined in order to detect point mutations with a possible effect in the affinity for azoles. Decreasing susceptibilities to FLC were detected in C. dubliniensis isolates recovered from both patients during the course of treatment. FLC-resistant C. dubliniensis isolates from one patient demonstrated combined upregulation of the MDR1, CDR1, and ERG11 genes. Among the isolates from the second patient, all isolates showing decreased susceptibility to FLC demonstrated upregulation of MDR1, whereas the levels of mRNA for the ERG11 genes remained constant and the expression of CDR genes was negligible. Fourteen point mutations were found in the ERG11 genes of the isolates with decreased susceptibility to FLC. These data demonstrate that the development of azole resistance in C. dublinensis clinical isolates from HIV-infected patients treated with FLC is mediated by multiple molecular mechanisms of resistance, similar to the observations found in the case of C. albicans.
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No. Sentence Comment
199 Nucleotide and amino acid substitutions in ERG11 genes from C. dubliniensis clinical isolates Patient no. Isolate FLC MIC (g/ml) Substitutiona S113F V125A F126L F148L T199A R210G D288G G289D L300P G307A R398G V437A G464S P515S 1 3300 1 T374C C378A T1310C 3946 64 C378A A595G A628G 4380 64 G1390A 4713 64 G1390A 4806 64 T442C G920C C1543T 4807 32 A863G T899C T1310C 5143 32 T374C C378A A1192G T1310C 2 3466 0.25 4572 64 C338T G866A a The base numbers are with respect to the first ATG codon of ERG11.
X
ABCB1 p.Val125Ala 12019078:199:157
status: NEW