ABCMdb

PMID: 11557454

Perea S, Lopez-Ribot JL, Kirkpatrick WR, McAtee RK, Santillan RA, Martinez M, Calabrese D, Sanglard D, Patterson TF
Prevalence of molecular mechanisms of resistance to azole antifungal agents in Candida albicans strains displaying high-level fluconazole resistance isolated from human immunodeficiency virus-infected patients.
Antimicrob Agents Chemother. 2001 Oct;45(10):2676-84., [PubMed]

Sentences

No. Mutations Sentence Comment

117 ABCB1 p.Val437Ile Two different point mutations that led to amino acid substitutions K128T and V437I were found in these isolates. Login to comment 119 ABCB1 p.Val437Ile Neither amino acid substitution (K128T or V437I) altered the affinity of Erg11p for fluconazole, and therefore, these substitutions are not associated with azole resistance. Login to comment 137 ABCB1 p.Val437Ile On the other hand, two amino acid substitutions, K128T and V437I, were confirmed to not participate in azole resistance, in agreement with previous reports (6, 33). Login to comment 142 ABCB1 p.Val437Ile Nucleotide and amino acid substitutions in ERG11 genes from C. albicans isolates Patient Isolate Fluconazole MIC (␮g/ml) Substitutiona D116E F126L K128T Y132F K143R T229A G307S S405F V437I D446N F449S G450E G464S 7 412 0.5 A383C 2307 Ͼ64 A383C 9 1002 0.25 2823 Ͼ64 3795 Ͼ64 T376C A428G 14 580 4 2440 64 G1309A 2500 64 G1309A 15 945 8 T348A G1349A 1619 64 T348A G919A G1349A 16 3107 4 A395T 3119 Ͼ64 A395T 3120 Ͼ64 A395T 3184 64 A395T 3281 64 A395T 28 5044 4 G1309A G1336A 5052 64 G1309A G1336A 30 5106 8 G1309A 5108 64 G1309A G1390A 42 1691 0.25 A383C 3731 Ͼ64 T376C A428G 3733 64 T376C A428G 43 1649 0.5 3034 Ͼ64 51 2274 16 C1214T 2257 64 C1214T 2339 64 C1214T 59 3917 4 T1346C 4617 64 A685G T1346C 4639 Ͼ64 A685G T1346C 64 4018 4 4380 64 G1309A a The base numbers are with respect to the first ATG codon of ERG11. Login to comment 164 ABCB1 p.Val437Ile ABCB1 p.Val437Ile ABCB1 p.Val437Ile ABCB1 p.Val437Ile ABCB1 p.Val437Ile C. albicans isolatea Mean Ϯ SD zone of inhibition (mm)b ERG11 allele expressed Amino acid substitution(s) 7 412 (S) 43.75 Ϯ 1.12 412 K128T 2307 (R) 43.08 Ϯ 0.90 2307 K128T 14 1632 (S) 42.80 Ϯ 1.93 580 None 1640 (R) 44.18 Ϯ 0.75 1640 V437I 15 945 (S) 32.50 Ϯ 0.70c 945 D116E, G450E 1619 (R) 0c 1619-1 D116E, G450E, G307S 32.80 Ϯ 1.35c 1619-2 D116E, G450E 16 3107 (S) 14.50 Ϯ 1.24c 3107 Y132F 3119 (R) 15.57 Ϯ 3.94c 3119 Y132F 28 5044 (S) 36.81 Ϯ 0.91c 5044 V437I, D446N 5052 (R) 37.56 Ϯ 2.00c 5052 V437I, D446N 30 5106 (S) 43.37 Ϯ 1.50 5106 V437I 5108 (R) 30.58 Ϯ 0.79c 5108 V437I, G464S 42 1691 (S) 42.87 Ϯ 0.83 1691 K128T 3731 (R) 0c 3731-1 F126L, K143R 22.33 Ϯ 0.52c 3731-2 K143R 51 2274 (S) 31.55 Ϯ 1.85c 2274 S405F 2257 (R) 33.16 Ϯ 1.83c 2257 S405F 2339 (R) 33.07 Ϯ 1.64c 2339 S405F 59 3917 (S) 42.62 Ϯ 1.50 3917-1 None 32.62 Ϯ 1.19c 3917-2 F449S 4617 (R) 21.05 Ϯ 0.87c 4617 F449S, T229A 4639 (R) 24.37 Ϯ 1.60c 4639 F449S, T229A a S, susceptible; R, resistant. Login to comment 177 ABCB1 p.Val437Ile ABCB1 p.Val437Ile ABCB1 p.Val437Ile ABCB1 p.Val437Ile ABCB1 p.Val437Ile ABCB1 p.Val437Ile ABCB1 p.Val437Ile ABCB1 p.Val437Ile ABCB1 p.Val437Ile Summary of amino acid substitutions in Erg11p and gene overexpression in fluconazole-resistant C. albicans isolates compared to matched susceptible isolates Patient Isolate Fluconazole MIC (␮g/ml) Amino acid substitutions in Erg11p Gene overexpression 7 412 0.5 K128T 2307 Ͼ64 K128T ERG11, CDR, CDR1, and CDR2 9 1002 0.25 2823 Ͼ64 ERG11, MDR1, and CDR2 ERG11 3795 Ͼ64 14 580 4 2440 64 V437I V437I, ERG11, and MDR1 2500 64 V437I V437I, ERG11, and MDR1 15 945 8 D116E and G450E 1619 64 D116E and G450E ERG11 and CDR2 16 3107 4 Y132F 3119 Ͼ64 Y132F MDR1 3120 Ͼ64 Y132F MDR1 3184 64 Y132F CDR 3281 64 Y132F CDR 28 5044 4 V437I and D446N 5052 64 V437I and D446N MDR1, CDR, CDR1, and CDR2 30 5106 8 V437I 5108 64 V437I and G464S ERG11, MDRI, CDR, and CDR1 42 1691 0.25 K128T 3731 Ͼ64 F126L and K143R MDR1 3733 64 F126L and K143R MDR1 43 1649 0.5 3034 Ͼ64 MDR1, CDR, CDR1, and CDR2 51 2274 16 S405F 2257 64 S405F 2339 64 S405F CDR, CDR1, and CDR2 59 3917 4 F449S 4617 64 F449S and T229A MDR1, CDR, and CDR1 4639 Ͼ64 F449S and T229A 64 4018 4 4380 64 V437I CDR, CDR1, and CDR2 the ERG11 gene for some of the substitutions identified; (ii) multiple isolates obtained from the same patient at different intervals exhibited the same or very similar polymorphisms, indicating a high degree of relatedness; and (iii) differences in nucleotide sequences among strains obtained from different patients indicate heterogeneity in the C. albicans population. Login to comment