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The Hsp90 Co-chaperones Sti1, Aha1, and P23 Regulate Adaptive Responses to Antifungal Azoles

Overview of attention for article published in Frontiers in Microbiology, October 2016
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Title
The Hsp90 Co-chaperones Sti1, Aha1, and P23 Regulate Adaptive Responses to Antifungal Azoles
Published in
Frontiers in Microbiology, October 2016
DOI 10.3389/fmicb.2016.01571
Pubmed ID
Authors

Xiaokui Gu, Wei Xue, Yajing Yin, Hongwei Liu, Shaojie Li, Xianyun Sun

Abstract

Heat Shock Protein 90 (Hsp90) is essential for tumor progression in humans and drug resistance in fungi. However, the roles of its many co-chaperones in antifungal resistance are unknown. In this study, by susceptibility test of Neurospora crassa mutants lacking each of 18 Hsp90/Calcineurin system member genes (including 8 Hsp90 co-chaperone genes) to antifungal drugs and other stresses, we demonstrate that the Hsp90 co-chaperones Sti1 (Hop1 in yeast), Aha1, and P23 (Sba1 in yeast) were required for the basal resistance to antifungal azoles and heat stress. Deletion of any of them resulted in hypersensitivity to azoles and heat. Liquid chromatography-mass spectrometry (LC-MS) analysis showed that the toxic sterols eburicol and 14α-methyl-3,6-diol were significantly accumulated in the sti1 and p23 deletion mutants after ketoconazole treatment, which has been shown before to led to cell membrane stress. At the transcriptional level, Aha1, Sti1, and P23 positively regulate responses to ketoconazole stress by erg11 and erg6, key genes in the ergosterol biosynthetic pathway. Aha1, Sti1, and P23 are highly conserved in fungi, and sti1 and p23 deletion also increased the susceptibility to azoles in Fusarium verticillioides. These results indicate that Hsp90-cochaperones Aha1, Sti1, and P23 are critical for the basal azole resistance and could be potential targets for developing new antifungal agents.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 36 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 36 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 10 28%
Student > Bachelor 6 17%
Student > Master 6 17%
Lecturer 2 6%
Student > Doctoral Student 1 3%
Other 4 11%
Unknown 7 19%
Readers by discipline Count As %
Agricultural and Biological Sciences 12 33%
Biochemistry, Genetics and Molecular Biology 10 28%
Immunology and Microbiology 2 6%
Medicine and Dentistry 1 3%
Chemistry 1 3%
Other 0 0%
Unknown 10 28%
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 05 October 2016.
All research outputs
#20,344,065
of 22,890,496 outputs
Outputs from Frontiers in Microbiology
#22,535
of 24,938 outputs
Outputs of similar age
#276,541
of 319,501 outputs
Outputs of similar age from Frontiers in Microbiology
#346
of 439 outputs
Altmetric has tracked 22,890,496 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 24,938 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.3. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 319,501 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 439 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.