Effects of Y132H and F145L Substitutions on the Activity, Azole Resistance and Spectral Properties of Candida albicans Sterol 14-Demethylase P450 (CYP51): A Live Example Showing the Selection of Altered P450 through Interaction with Environmental Compounds

2005 ◽  
Vol 137 (5) ◽  
pp. 625-632 ◽  
Author(s):  
Makiko Kudo ◽  
Miwa Ohi ◽  
Yuri Aoyama ◽  
Yuko Nitahara ◽  
Sung-Kee Chung ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Spectral Properties ◽  
Azole Resistance ◽  
Selection Of

scholarly journals Development and Validation of a High-Resolution Melting Assay To Detect Azole Resistance in Aspergillus fumigatus

2017 ◽  
Vol 61 (12) ◽  
Author(s):  
L. Bernal-Martínez ◽  
H. Gil ◽  
O. Rivero-Menéndez ◽  
S. Gago ◽  
M. Cuenca-Estrella ◽  
...  
Keyword(s):  
High Resolution ◽  
Aspergillus Fumigatus ◽  
Tandem Repeats ◽  
High Resolution Melting ◽  
Screening Method ◽  
Melting Curve ◽  
Health Concern ◽  
Azole Resistance ◽  
Content Type ◽  
Selection Of

ABSTRACT The global emergence of azole-resistant Aspergillus fumigatus strains is a growing public health concern. Different patterns of azole resistance are linked to mutations in cyp51A. Therefore, accurate characterization of the mechanisms underlying azole resistance is critical to guide selection of the most appropriate antifungal agent for patients with aspergillosis. This study describes a new sequencing-free molecular screening tool for early detection of the most frequent mutations known to be associated with azole resistance in A. fumigatus. PCRs targeting cyp51A mutations at positions G54, Y121, G448, and M220 and targeting different tandem repeats (TRs) in the promoter region were designed. All PCRs were performed simultaneously, using the same cycling conditions. Amplicons were then distinguished using a high-resolution melting assay. For standardization, 30 well-characterized azole-resistant A. fumigatus strains were used, yielding melting curve clusters for different resistance mechanisms for each target and allowing detection of the most frequent azole resistance mutations, i.e., G54E, G54V, G54R, G54W, Y121F, M220V, M220I, M220T, M220K, and G448S, and the tandem repeats TR34, TR46, and TR53. Validation of the method was performed using a blind panel of 80 A. fumigatus azole-susceptible or azole-resistant strains. All strains included in the blind panel were properly classified as susceptible or resistant with the developed method. The implementation of this screening method can reduce the time needed for the detection of azole-resistant A. fumigatus isolates and therefore facilitate selection of the best antifungal therapy in patients with aspergillosis.

scholarly journals Candida albicans gains azole resistance by altering sphingolipid composition

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Jiaxin Gao ◽  
Haitao Wang ◽  
Zeyao Li ◽  
Ada Hang-Heng Wong ◽  
Yi-Zheng Wang ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Azole Resistance

Selection of potential anti-adhesion drugs by in silico approaches targeted to ALS3 from Candida albicans

2019 ◽  
Vol 41 (12) ◽  
pp. 1391-1401 ◽  
Author(s):  
Erika Seki Kioshima ◽  
Cristiane Suemi Shinobu-Mesquita ◽  
Ana Karina Rodrigues Abadio ◽  
Maria Sueli Soares Felipe ◽  
Terezinha Inez Estivalet Svidzinski ◽  
...  
Keyword(s):  
Candida Albicans ◽  
In Silico ◽  
Selection Of

scholarly journals Genetic Analysis of Azole Resistance in the Darlington Strain of Candida albicans

2000 ◽  
Vol 44 (11) ◽  
pp. 2985-2990 ◽  
Author(s):  
Hiroshi Kakeya ◽  
Yoshitsugu Miyazaki ◽  
Haruko Miyazaki ◽  
Katherine Nyswaner ◽  
Brian Grimberg ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acids ◽  
Candida Albicans ◽  
Amino Acid ◽  
Genetic Analysis ◽  
Expression System ◽  
Single Copy ◽  
Gene Replacement ◽  
Azole Resistance ◽  
High Level

ABSTRACT High-level azole resistance in the Darlington strain ofCandida albicans was investigated by gene replacement inC. albicans and expression in Saccharomyces cerevisiae. We sequenced the ERG11 gene, which encodes the sterol C14α-demethylase, from our copy of the Darlington strain. Both alleles contained the histidine for tyrosine substitution at position 132 (Y132H) reported in Darlington by others, but we also found a threonine-for-isoleucine substitution (I471T) not previously reported in the C. albicans ERG11. The encoded I471T change in amino acids conferred azole resistance when overexpressed alone and increased azole resistance when added to the Y132H amino acid sequence in an S. cerevisiae expression system. Replacement of one copy of ERG11 in an azole-susceptible strain of C. albicans with a single copy of the Darlington ERG11 resulted in expression of the integrated copy and a modest increase in azole resistance. The profound azole resistance of the Darlington strain is the result of multiple mutations.

scholarly journals Principles of a New Protocol for Prediction of Azole Resistance in Candida albicans Infections on the Basis of ERG11 Polymorphisms

2016 ◽  
Vol 73 (2) ◽  
pp. 172-182 ◽  
Author(s):  
Monika Caban ◽  
Dominik Strapagiel ◽  
Jarosław Dziadek ◽  
Małgorzata Korycka-Machała ◽  
Agnieszka Grzelak
Keyword(s):  
Candida Albicans ◽  
Azole Resistance

scholarly journals Contribution of mutations in the cytochrome P450 14α-demethylase (Erg11p, Cyp51p) to azole resistance in Candida albicans

Microbiology ◽  
1999 ◽  
Vol 145 (10) ◽  
pp. 2701-2713 ◽  
Author(s):  
Patrick Marichal ◽  
Luc Koymans ◽  
Staf Willemsens ◽  
Danny Bellens ◽  
Peter Verhasselt ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Candida Albicans ◽  
Azole Resistance

scholarly journals Genetic Architecture of Hsp90-Dependent Drug Resistance

2006 ◽  
Vol 5 (12) ◽  
pp. 2184-2188 ◽  
Author(s):  
Leah E. Cowen ◽  
Anne E. Carpenter ◽  
Oranart Matangkasombut ◽  
Gerald R. Fink ◽  
Susan Lindquist
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Drug Resistance ◽  
Candida Albicans ◽  
Genetic Architecture ◽  
Opportunistic Pathogen ◽  
Azole Resistance

ABSTRACT Hsp90 potentiates the evolution of azole resistance in the model yeast Saccharomyces cerevisiae and the opportunistic pathogen Candida albicans via calcineurin. Here, we explored effectors downstream of calcineurin regulating this Hsp90-dependent trait. Using S. cerevisiae erg3 mutants as a model, we determined that both Crz1 and Hph1 modulate azole resistance.

scholarly journals Genome-Wide Expression Profile Analysis Reveals Coordinately Regulated Genes Associated with Stepwise Acquisition of Azole Resistance in Candida albicans Clinical Isolates

2003 ◽  
Vol 47 (4) ◽  
pp. 1220-1227 ◽  
Author(s):  
P. David Rogers ◽  
Katherine S. Barker
Keyword(s):  
Candida Albicans ◽  
Expression Profile ◽  
Profile Analysis ◽  
Clinical Isolates ◽  
Azole Resistance ◽  
Down Regulation ◽  
Human Fungal Pathogen ◽  
Expression Profile Analysis ◽  
Genome Wide ◽  
First Time

ABSTRACT Candida albicans is an opportunistic human fungal pathogen and a causative agent of oropharyngeal candidiasis (OPC), the most frequent opportunistic infection among patients with AIDS. Fluconazole and other azole antifungal agents have proven effective in the management of OPC; however, with increased use of these agents treatment failures have occurred. Such failures have been associated with the emergence of azole-resistant strains of C. albicans. In the present study we examined changes in the genome-wide gene expression profile of a series of C. albicans clinical isolates representing the stepwise acquisition of azole resistance. In addition to genes previously associated with azole resistance, we identified many genes whose differential expression was for the first time associated with this phenotype. Furthermore, the expression of these genes was correlated with that of the known resistance genes CDR1, CDR2, and CaMDR1. Genes coordinately regulated with the up-regulation of CDR1 and CDR2 included the up-regulation of GPX1 and RTA3 and the down-regulation of EBP1. Genes coordinately regulated with the up-regulation of CaMDR1 included the up-regulation of IFD1, IFD4, IFD5, IFD7, GRP2, DPP1, CRD2, and INO1 and the down-regulation of FET34, OPI3, and IPF1222. Several of these appeared to be coordinately regulated with both the CDR genes and CaMDR1. Many of these genes are involved in the oxidative stress response, suggesting that reduced susceptibility to oxidative damage may contribute to azole resistance. Further evaluation of the role these genes and their respective gene products play in azole antifungal resistance is warranted.

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