ArticleFuture microbiology2025
Proteomics and β-hydroxybutyrylome reveal the novel mechanisms underlying fluconazole resistance in
Article in Future microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundThe rising incidence of fluconazole-resistant
aimTo delineate the proteomic and β-hydroxybutyrylome changes associated with fluconazole resistance and identify potential novel therapeutic approaches.
methodsWe performed comprehensive proteomic and β-hydroxybutyrylome analyses on fluconazole-resistant and -susceptible
resultsProteomic profiling exhibited significant dysregulation of acylation-modulating enzymes, notably downregulation of histone acetyltransferase RTT109 and upregulation of deacetylase HDA1. WB confirmed pronounced suppression of β-hydroxybutyrylation in the resistant strain. Combination therapy reduced the minimum inhibitory concentration values of fluconazole and BHB by 64-fold and 4-fold, respectively, indicating a synergistic interaction. β-hydroxybutyrylome profiling identified 27 significantly upregulated sites on 27 proteins and 91 downregulated sites on 86 proteins in the resistant strain, consistent with WB data. Bioinformatic analyses implicated alterations in β-hydroxybutyrylation of metabolic pathway proteins as a key mechanism underlying the development of fluconazole resistance.
conclusionFluconazole-resistant
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