ABCMdb

ABCB1 p.Ala354Gly

Predicted by SNAP2:	C: D (53%), D: D (59%), E: D (75%), F: D (66%), G: D (66%), H: N (57%), I: N (53%), K: D (75%), L: D (59%), M: D (71%), N: N (61%), P: D (80%), Q: D (71%), R: D (75%), S: N (82%), T: N (78%), V: N (57%), W: D (80%), Y: N (61%),
Predicted by PROVEAN:	C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: N, T: N, V: D, W: D, Y: D,

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[hide] Selected mechanisms of molecular resistance of Can... Acta Biochim Pol. 2015;62(2):247-51. doi: 10.18388/abp.2014_940. Epub 2015 Apr 21. Golabek K, Strzelczyk JK, Owczarek A, Cuber P, Slemp-Migiel A, Wiczkowski A
Selected mechanisms of molecular resistance of Candida albicans to azole drugs.
Acta Biochim Pol. 2015;62(2):247-51. doi: 10.18388/abp.2014_940. Epub 2015 Apr 21., [PMID:25901298]

Abstract [show]
A phenomenon of increasing resistance of Candida spp. to azoles has been observed for several years now. One of the mechanisms of lack of sensitivity to azoles is associated with CDR1, CDR2, MRD1 genes (their products are active transport pumps conditioning drug efflux from pathogen's cell), and ERG11 gene (encoding lanosterol 14alpha-demethylase). Test material was 120 strains of Candida albicans (60 resistant and 60 susceptible to azole drugs) obtained from clinical samples. The first stage of experiment assessed the expression of CDR1, CDR2, MDR1 and ERG11 genes by Q-PCR. The impact of ERG11 gene's mutations on the expression of this gene was analysed. The final stage of the experiment assessed the level of genome methylation of Candida albicans strains. An increase in the expression of CDR2, MDR1 and ERG11 was observed in azole-resistant strains of Candida albicans in comparison to strains sensitive to this class of drugs. Furthermore, 19 changes in the sequence of ERG11 were detected in tested strains. Four of the discovered mutations: T495A, A530C, G622A and A945C led to the following amino acid substitutions: D116E, K128T, V159I and E266D, respectively. It has also been found that statistically five mutations: T462C, G1309A, C216T, C1257T and A945C affected the expression of ERG11. The applied method of assessing the level of methylation of Candida albicans genome did not confirm its role in the development of resistance to azoles. The results indicate however, that resistance of Candida albicans strains to azole drugs is multifactorial.

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90 Sequence analysis of the ERG11 gene in the studied Candida albicans strains revealed 19 different mutations: T462C, T495A, A504G, A530C, C558T, G622A, C216T, A354G, A1587G, T1617C, G1309A, T1143C, A1167G, A1173G, A1230G, C1257T, T1287C, A945C, T1203C. Login to comment
92 Mutations C558T and A354G were common only in azole-sensitive strains of Candida albicans. Login to comment