{"title":"Effects of the HDAC6/8 Inhibitor MC1568, Alone and in Combination With Fluconazole, in Non-Albicans Candida Species Infections","authors":"Andrea Giammarino, Chiara Lambona, Alessia Raucci, Giovanna Simonetti, Salvatore Macrì, Angela Iuzzolino, Daniela Trisciuoglio, Sergio Valente, Gustavo Giusiano, Letizia Angiolella, Antonello Mai","doi":"10.1002/mbo3.70188","DOIUrl":null,"url":null,"abstract":"<p>Fungal infections pose a severe health risk, particularly in immunocompromised individuals, with <i>Candida</i> species being a leading cause of bloodstream infections. The rise of non-<i>albicans Candida</i> (NAC) infections, accounting for 35%–65% of candidemia cases, underscores the urgent need for novel antifungal strategies. Current treatments, including echinocandins and azoles, are increasingly challenged by drug-resistant strains. This study evaluated the antifungal efficacy of three clinically approved histone deacetylase inhibitors (HDACi)—Vorinostat, Romidepsin, and Tucidinostat—along with the HDAC6/8-selective inhibitor MC1568, alone and in combination with Fluconazole. The Fluconazole/MC1568 combination exhibited significant synergistic effects, reducing biofilm formation and enhancing antifungal activity, particularly against <i>C. guillermondii</i>, <i>C. lusitaniae</i>, and <i>C. tropicalis</i>. In <i>Galleria mellonella</i> larvae, this combination increased survival by 70% in <i>C. tropicalis</i> infections. When tested in human retinal pigment epithelium (RPE) cells, three different MC1568/Fluconazole combinations displayed low toxicity. These findings highlight the potential of the HDAC6/8 inhibitor MC1568 as adjunct therapy to combat NAC infections, warranting further research to optimize antifungal efficacy while minimizing toxicity.</p>","PeriodicalId":18573,"journal":{"name":"MicrobiologyOpen","volume":"15 4","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mbo3.70188","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"MicrobiologyOpen","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/mbo3.70188","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Fungal infections pose a severe health risk, particularly in immunocompromised individuals, with Candida species being a leading cause of bloodstream infections. The rise of non-albicans Candida (NAC) infections, accounting for 35%–65% of candidemia cases, underscores the urgent need for novel antifungal strategies. Current treatments, including echinocandins and azoles, are increasingly challenged by drug-resistant strains. This study evaluated the antifungal efficacy of three clinically approved histone deacetylase inhibitors (HDACi)—Vorinostat, Romidepsin, and Tucidinostat—along with the HDAC6/8-selective inhibitor MC1568, alone and in combination with Fluconazole. The Fluconazole/MC1568 combination exhibited significant synergistic effects, reducing biofilm formation and enhancing antifungal activity, particularly against C. guillermondii, C. lusitaniae, and C. tropicalis. In Galleria mellonella larvae, this combination increased survival by 70% in C. tropicalis infections. When tested in human retinal pigment epithelium (RPE) cells, three different MC1568/Fluconazole combinations displayed low toxicity. These findings highlight the potential of the HDAC6/8 inhibitor MC1568 as adjunct therapy to combat NAC infections, warranting further research to optimize antifungal efficacy while minimizing toxicity.
期刊介绍：
MicrobiologyOpen is a peer reviewed, fully open access, broad-scope, and interdisciplinary journal delivering rapid decisions and fast publication of microbial science, a field which is undergoing a profound and exciting evolution in this post-genomic era.
The journal aims to serve the research community by providing a vehicle for authors wishing to publish quality research in both fundamental and applied microbiology. Our goal is to publish articles that stimulate discussion and debate, as well as add to our knowledge base and further the understanding of microbial interactions and microbial processes.
MicrobiologyOpen gives prompt and equal consideration to articles reporting theoretical, experimental, applied, and descriptive work in all aspects of bacteriology, virology, mycology and protistology, including, but not limited to:
- agriculture
- antimicrobial resistance
- astrobiology
- biochemistry
- biotechnology
- cell and molecular biology
- clinical microbiology
- computational, systems, and synthetic microbiology
- environmental science
- evolutionary biology, ecology, and systematics
- food science and technology
- genetics and genomics
- geobiology and earth science
- host-microbe interactions
- infectious diseases
- natural products discovery
- pharmaceutical and medicinal chemistry
- physiology
- plant pathology
- veterinary microbiology
We will consider submissions across unicellular and cell-cluster organisms: prokaryotes (bacteria, archaea) and eukaryotes (fungi, protists, microalgae, lichens), as well as viruses and prions infecting or interacting with microorganisms, plants and animals, including genetic, biochemical, biophysical, bioinformatic and structural analyses.
The journal features Original Articles (including full Research articles, Method articles, and Short Communications), Commentaries, Reviews, and Editorials. Original papers must report well-conducted research with conclusions supported by the data presented in the article. We also support confirmatory research and aim to work with authors to meet reviewer expectations.
MicrobiologyOpen publishes articles submitted directly to the journal and those referred from other Wiley journals.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
