ABCMdb

ABCB1 p.Val437Ile

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Publications

PMID: 11557454 [PubMed] Perea S et al: "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."

No. Sentence Comment

117 Two different point mutations that led to amino acid substitutions K128T and V437I were found in these isolates. Login to comment
119 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 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 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 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 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

PMID: 12019079 [PubMed] White TC et al: "Resistance mechanisms in clinical isolates of Candida albicans."

No. Sentence Comment

211 Five mutations, located in the three hot spots, were observed in the three complete sequences; these mutations included D116E, K128T, K143R, E266D, and V437I (Table 2). Login to comment
214 Both of these mutations were also found in isolate 11 and were present in the first hot spot. Isolate 4 was heterozygous for D116E/D in the first hot spot, homozygous for E266D in the second hot spot, and heterozygous for V437I/V in the third hot spot. Login to comment
216 The V437I mutation was homozygous in isolates 5 and 22 (Table 2). Login to comment
218 Of these six mutations, the D116E, K128T, K143R, E266D, and V437I mutations have been described in isolates from other studies (18). Login to comment
239 Protein sequence alterations associated with resistancea Mutation Result for isolates whose complete gene was sequenced Result for isolates for which the hot spot III region was sequenced 4 7 11 3 5 8 9 22 D116E Heterozyg. Heterozyg. Homozyg. K128T WT Heterozyg. Homozyg. K143R WT WT Homozyg. E266D Homozyg. WT WT V437I Heterozyg. WT WT WT Homozyg. WT WT Homozyg. G448R WT WT WT WT WT Homozyg. WT WT a Point mutations that resulted in amino acid changes identified by sequencing of ERG11 from the indicated isolates. Login to comment

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

No. Sentence Comment

221 Four homozygousnucleotide changes leading to aminoacidsubs- titutions E266D, V404I, V437I and V509M were found in the two Table 1. Login to comment

PMID: 15155210 [PubMed] Chau AS et al: "Application of real-time quantitative PCR to molecular analysis of Candida albicans strains exhibiting reduced susceptibility to azoles."

No. Sentence Comment

116 MIC and RT-PCR data for SPRI azole-susceptible C. albicans isolates Isolate MICa (␮g/mL) ⌬CT Substitution(s) in Erg11p POS ITZ FLZ VOR ACT1 PMA1 ERG11 MDR1 CDR1 CDR2 C34 0.016 0.06 0.25 Ͻ0.004 8.1 7.1 10.3 11.1 11.3 13.5 None C40 0.016 0.06 0.25 Ͻ0.004 7.2 6.2 10.6 11.9 9.6 14.1 D116E, K128Tb C43 Ͻ0.03 0.06 0.25 0.03 7.4 6.3 10.3 15.1 10.2 14.4 NDc C60 0.016 0.06 Ͻ0.12 Ͻ0.004 7.6 6.3 8.6 10.9 11.8 15.9 None C72 0.03 0.06 0.06 Ͻ0.008 7.9 6.7 8.7 12.0 10.4 12.5 D116E C84 0.008 0.06 Ͻ0.12 Ͻ0.004 7.3 6.4 9.3 14.4 10.2 13.8 D116E C128 0.008 0.03 Ͻ0.12 Ͻ0.004 7.5 6.1 11.1 14.4 10.5 14.6 D116E, K128T,b D496 C132 0.016 0.06 0.25 Ͻ0.004 7.5 5.8 11.3 13.2 10.0 14.5 D116E, K128Tb C294 0.008 0.016 0.25 Ͻ0.008 8.9 8.3 10.9 12.8 12.3 16.0 None C392 Ͻ0.004 0.03 0.5 Ͻ0.008 7.9 6.7 11.1 14.0 11.2 14.6 None C393 Ͻ0.004 0.016 0.25 Ͻ0.008 7.8 6.7 11.3 13.0 10.7 14.7 ND C394 Ͻ0.004 0.016 0.25 Ͻ0.008 7.9 6.3 10.9 16.6 10.6 13.9 ND C395 Ͻ0.004 0.016 0.25 Ͻ0.008 7.9 6.8 11.5 12.4 10.7 15.6 V437I C548 Ͻ0.004 Ͻ0.008 Ͻ0.125 Ͻ0.008 7.6 6.3 10.0 14.2 12.3 14.4 V437I Avg ⌬CT 7.8 6.6 10.4 13.6 10.8 14.5 SD 0.4 0.6 0.9 2 0.8 0.9 3-SD range 6.6-9.0 4.8-8.4 7.7-13.1 7.6-19.6 8.4-13.2 11.8-17.2 a POS, posaconazole; ITZ, itraconazole; FLZ, fluconazole; VOR, voriconazole. Login to comment

PMID: 9797228 [PubMed] Lopez-Ribot JL et al: "Distinct patterns of gene expression associated with development of fluconazole resistance in serial candida albicans isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis."

No. Sentence Comment

111 For these two isolates, the only nucleotide change that had an effect in the amino acid sequence was the single amino acid substitution V437I. Login to comment

PMID: 16621465 [PubMed] Cernicka J et al: "Resistance mechanisms in fluconazole-resistant Candida albicans isolates from vaginal candidiasis."

No. Sentence Comment

81 With the exception of K128T, E266D and V437I [15,32], no data are available regarding the confirmed participation in azole resistance of other amino acid substitutions resulting from our ERG11 sequenced amplicons. Login to comment
92 FLU and 4-NQO, but not ITR and TER, are acknowledged substrates of this efflux pump [18,27,33] belonging to the class Table 2 Amino acid substitutions in Erg11p from Candida albicans isolatesa Candida albicans isolate Amino acid substitutions Allelic state of mutation 63 D116E Heterozygous K128T Heterozygous 193 P49R/T Heterozygous E266D Homozygous T486P Heterozygous V488I Homozygous 208 D116E Heterozygous K119L Heterozygous E266D Heterozygous 222 E266D Homozygous V488I Homozygous 235 Y33C Heterozygous Y39C Heterozygous W54Stop Heterozygous V437I Homozygous L491V Heterozygous T494A Heterozygous a Substitutions conserved in fluconazole-resistant strains are written in bold. Login to comment

PMID: 25748216 [PubMed] Liu JY et al: "Mechanisms of azole resistance in Candida albicans clinical isolates from Shanghai, China."

No. Sentence Comment

103 of strainsa Site of isolation FLC ITRA VRC Amino acid substitution(s) in Tac1b Missense mutation in TAC1 gene Amino acid substitution(s) in Erg11b Missense mutation in ERG11 gene Gene overexpression Y141 Vagina 16(SDD) >16(R) 0.5(S) S199N, A736V, L935S G596A, C2207T, T2804C A114S, Y205E, Y257H, V437I G340T, T613G or C615A, T769C, G1309A CDR2 Y201 Vagina 16(SDD) 16(R) 1(S) F104V, A736V, L935S T310G, C2207T, T2804C A114S, Y205E, Y257H, V437I G340T, T613G or C615A, T769C, G1309A CDR1 Y205 Vagina 16(SDD) 0.5(SDD) 2(I) D776N, L935S G2326A, T2804C Y132H, Y205E,V437I, G448E T394C, T613G or C615A, G1309A, G1343A CDR1,CDR2 Y206 Vagina 16(SDD) 16(R) 2(I) S199N, D776N, L935S G596A, G2326A, T2804C Y132H, Y205E, V437I, G472R T394C, T613G or C615A, G1309A, G1414A CDR2 Y208 Vagina 32(SDD) 16(R) 1(S) e e Y132H, Y205E, N435V, G448E,D502E T394C, T613G or C615A, A1303G, G1343A, C1506A e Y210 Vagina 16(SDD) 0.25(SDD) 4(R) S199N, N772K, N896S G596A, T2316A, A2687G Y132H, Y205E, Y257H, E260V, V437I, G448E T394C, T613G or C615A, T769C, A779T, G1309A, G1343A CDR1,CDR2 Y203 Vagina 0.5(S) 0.0313(S) <0.0313(S) S199N, L935S G596A, T2804C Y205E, V437I T613G or C615A, G1309A e J026 Sputum 0.5(S) 0.0313(S) 0.0313(S) e e Y205E, V437I T613G or C615A, G1309A e J509 Vagina 32(SDD) 0.25(SDD) 0.25(S) S199N, D776N, L935S G596A, G2326A, T2804C D116E, K128T, Y205E, V437I T348A, A383C, T613G or C615A, G1309A CDR2 J774 Sputum 0.5(S) 0.0313(S) <0.0313(S) e e Y205E, V437I T613G or C615A, G1309A e J5039 Sputum 2(S) 0.0313(S) <0.0313(S) F104V, L935S T310G, T2804C D116E T348A e J5043 Sputum 2(S) 0.0313(S) <0.0313(S) e e Y205E, V437I T613G or C615A, G1309A e H24308 Skin 32(SDD) 0.5(SDD) 0.25(S) S199N, D776N G596A, G2326A, D116E, K128T, K143R, Y205E, V437I T348A, A383C, A428G, T613G or C615A, G1309A CDR2 H75045 Vagina 16(SDD) 0.25(SDD) 2(I) S199N, L935S, F964Y G596A, T2804C, A2890G or A2891T Y132H, Y205E, V437I, G448E T394C, T613G or C 615A, G1309A, G1343A CDR1,CDR2,ERG11 H13139 Skin >64(R) >16(R) 8(R) e e D116E, Y132F, K143Q, Y205E, Y257H T348A, A395T, A427C, T613G or C615A, T769C e H21897 Skin >64(R) >16(R) 16(R) S199N, N772K, N896S G596A, T2316A, A2687G D116E, Y132F, K143Q, Y205E, V437I T348A, A395T, A427C, T613G or C615A, G1309A CDR1,CDR2 H64110 Skin >64(R) 16(R) 4(R) e e D116E, Y132F, K143Q, Y205E, Y257H T348A, A395T, A427C, T613G or C615A, T769C e H30071 Sputum 4(S) <0.0313(S) 0.0313(S) e e D116E T348A e Rc701 Sputum 0.25(S) 0.0313(S) <0.0313(S) e e Y205E, V437I T613G or C615A, G1309A e RC837 Sputum 0.25(S) 0.0313(S) <0.0313(S) S199N, L935S G596A, T2804C D116E T348A e Rc924 Sputum 0.125(S) <0.0313(S) <0.0313(S) F104V, L935S T310G, T2804C Y205E,E226D,V437I T613G or C615A, A789C, G1309A e Rc289 Throat 0.25(S) 0.0313(S) 0.0313(S) e e Y205E, V437I T613G or C615A, G1309A e Rc273 Sputum 0.25(S) <0.0313(S) 0.0313(S) e e D116E, V437I T348A, G1309A e Rc923 Sputum 0.25(S) 0.0313(S) 0.0313(S) S199N, L935S G596A, T2804C Y205E, A255V, V437I T613G or C615A, C764T, G1309A e Rc592 Sputum 0.25(S) 0.0313(S) <0.0313(S) e e D116E, Y205E T348A, T613G or C615A e Rc271 Stool 0.25(S) <0.0313(S) <0.0313(S) F104V, L935S T310G, T2804C D116E, V437I T348A, G1309A e Rc286 Sputum 0.25(S) 0.0313(S) 0.0313(S) e Y205E, V437I T613G or C615A, G1309A e Rc944 Sputum 1(S) 0.0313(S) 0.0313(S) e D116E T348A e Rc963 Throat 0.25(S) 0.0313(S) 0.0313(S) e Y205E, V437I T613G or C615A, G1309A e Rc827 Sputum 0.125(S) <0.0313(S) <0.0313(S) e Y205E, V437I T613G or C615A, G1309A e a Y, Shanghai First Maternity and Infant Hospital at Tonji University School of Medicine. Login to comment