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Structural basis for heterogeneous phenotype of ERG11 dependent Azole resistance in C.albicans clinical isolates

Overview of attention for article published in SpringerPlus, November 2014
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Title
Structural basis for heterogeneous phenotype of ERG11 dependent Azole resistance in C.albicans clinical isolates
Published in
SpringerPlus, November 2014
DOI 10.1186/2193-1801-3-660
Pubmed ID
Authors

Surajit Debnath, Soma Addya

Abstract

Correlating antifungal Azole drug resistance and mis-sense mutations of ERG11 has been paradoxical in pathogenic yeast Candida albicans. Amino acid substitutions (single or multiple) are frequent on ERG11, a membrane bound enzyme of Ergosterol biosynthesis pathway. Presence or absence of mutations can not sufficiently predict susceptibility. To analyze role of mis-sense mutations on Azole resistance energetically optimized, structurally validated homology model of wild C.albicans ERG11 using eukaryotic template was generated. A Composite Search Approach is proposed to identify vital residues for interaction at 3D active site. Structural analysis of catalytic groove, dynamics of substrate access channels and proximity of Heme prosthetic group characterized ERG11 active site. Several mis-sense mutations of ERG11 reported in C.albicans clinical isolates were selected through a stringent criterion and modeled. ERG11 mutants subsequently subjected to a four tier comparative biophysical analysis. This study indicates (i) critical interactions occur with residues at anterior part of 3D catalytic groove and substitution of these vital residues alters local geometry causing considerable change in catalytic pocket dimension. (ii) Substitutions of vital residues lead to confirmed resistance in clinical isolates that may be resultant to changed geometry of catalytic pocket. (iii)These substitutions also impart significant energetic changes on C.albicans ERG11 and (iv) include detectable dynamic fluctuations on the mutants. (v)Mis-sense mutations on the vital residues of the active site and at the vicinity of Heme prosthetic group are less frequent compared to rest of the enzyme. This large scale mutational study can aid to characterize the mutants in clinical isolates.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 32 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Denmark 1 3%
Unknown 31 97%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 16%
Researcher 5 16%
Student > Master 4 13%
Student > Bachelor 3 9%
Other 2 6%
Other 6 19%
Unknown 7 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 28%
Agricultural and Biological Sciences 9 28%
Immunology and Microbiology 2 6%
Medicine and Dentistry 2 6%
Unspecified 1 3%
Other 1 3%
Unknown 8 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 December 2014.
All research outputs
#20,247,117
of 22,775,504 outputs
Outputs from SpringerPlus
#1,461
of 1,852 outputs
Outputs of similar age
#219,237
of 262,800 outputs
Outputs of similar age from SpringerPlus
#85
of 97 outputs
Altmetric has tracked 22,775,504 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,852 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.7. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 97 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.