Keyword search (4,163 papers available)

"UV" Keyword-tagged Publications:

Title Authors PubMed ID
1 Recruitment dynamics of juvenile salmonids: Comparisons among populations and with classic case studies Matte JO; Fraser DJ; Grant JWA; 38599588
BIOLOGY
2 Discovery of an adjuvant that resensitizes polymyxin B-resistant bacteria Mahdavi M; Findlay BL; 38096681
BIOLOGY
3 Understanding Fluconazole Tolerance in Candida albicans: Implications for Effective Treatment of Candidiasis and Combating Invasive Fungal Infections Feng Y; Lu H; Whiteway M; Jiang Y; 37918789
BIOLOGY
4 Cross-collection latent Beta-Liouville allocation model training with privacy protection and applications Luo Z; Amayri M; Fan W; Bouguila N; 36685642
ENCS
5 Stable Cavitation-Mediated Delivery of miR-126 to Endothelial Cells He S; Singh D; Yusefi H; Helfield B; 36559150
BIOLOGY
6 A Small Molecule Inhibitor of Erg251 Makes Fluconazole Fungicidal by Inhibiting the Synthesis of the 14α-Methylsterols Lu H; Li W; Whiteway M; Wang H; Zhu S; Ji Z; Feng Y; Yan L; Fang T; Li L; Ni T; Zhang X; Lv Q; Ding Z; Qiu L; Zhang D; Jiang Y; 36475771
BIOLOGY
7 Pattern and Visual Prognostic Factors of Behcet's Uveitis in Northwest Iran Alizadeh Ghavidel L; Bagheri M; Mousavi F; Rezaei L; Hazeri S; Hashemi HS; 35765637
BIOLOGY
8 Removal of SARS-CoV-2 using UV+Filter in built environment: simulation/evaluation by utilizing validated numerical method Feng Z; Cao SJ; Haghighat F; 34367884
ENCS
9 Drug discovery and chemical probing in Drosophila. Millet-Boureima C, Selber-Hnatiw S, Gamberi C 32551911
BIOLOGY
10 Early Life History of Coreoperca herzi in Han River, Korea. Park JM, Jeon HB, Suk HY, Cho SJ, Han KH 32411919
BIOLOGY
11 Population variation in density-dependent growth, mortality and their trade-off in a stream fish. Matte JM, Fraser DJ, Grant JWA 31642512
BIOLOGY

 

Title:A Small Molecule Inhibitor of Erg251 Makes Fluconazole Fungicidal by Inhibiting the Synthesis of the 14α-Methylsterols
Authors:Lu HLi WWhiteway MWang HZhu SJi ZFeng YYan LFang TLi LNi TZhang XLv QDing ZQiu LZhang DJiang Y
Link:https://pubmed.ncbi.nlm.nih.gov/36475771/
DOI:10.1128/mbio.02639-22
Publication:mBio
Keywords:Candida albicansErg251fluconazole adjuvantfluconazole tolerancesmall molecule inhibitor
PMID:36475771 Category: Date Added:2022-12-08
Dept Affiliation: BIOLOGY
1 Department of Pharmacy, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
2 Department of Biology, Concordia University, Montreal, Quebec, Canada.
3 Department of Physiology and Pharmacology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China.
4 School of Pharmacy, Naval Medical University, Shanghai, China.

Description:

Fluconazole (FLC) is widely used to prevent and treat invasive fungal infections. However, FLC is a fungistatic agent, allowing clinical FLC-susceptible isolates to tolerate FLC. Making FLC fungicidal in combination with adjuvants is a promising strategy to avoid FLC resistance and eliminate the persistence and recurrence of fungal infections. Here, we identify a new small molecule compound, CZ66, that can make FLC fungicidal. The mechanism of action of CZ66 is targeting the C-4 sterol methyl oxidase, encoded by the ERG251 gene, resulting in decreased content of sterols with the 14a-methyl group and ultimately eliminating FLC tolerance of Candida albicans. CZ66 most likely interacts with Erg251 through residues Glu195, Gly206, and Arg241. Establishing Erg251 as a synergistic lethal target protein of FLC should direct research to identify specific small molecule inhibitors of 14a-methylsterol synthesis and open the way to abolishing fungal FLC tolerance. IMPORTANCE Fluconazole (FLC) tolerance increases the frequency of acquired FLC resistance, and a high FLC tolerance level is associated with persistent candidemia. Multiple functional proteins, such as calcineurin, heat shock protein 90 (Hsp90), and ADP ribosylation factor, are essential for the survival of C. albicans exposed to FLC, but how these factors increase the fungicidal activity of FLC remains to be determined. In this study, we found that 14a-methylsterols replace ergosterol to allow C. albicans to survive FLC, but Erg251 inactivated by CZ66 results in loss of 14a-methylsterol synthesis and cell death of C. albicans treated with FLC. Establishing Erg251 as a synergistic lethal target protein of FLC should direct research to identify specific small molecule inhibitors of 14a-methylsterol synthesis and open the way to abolishing fungal FLC tolerance.





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