Related Experiment Video

Updated: Jul 9, 2026

Candida albicans Biofilm Chip (CaBChip) for High-throughput Antifungal Drug Screening
08:05

Candida albicans Biofilm Chip (CaBChip) for High-throughput Antifungal Drug Screening

Published on: July 18, 2012

Effects of the HDAC6/8 Inhibitor MC1568, Alone and in Combination With Fluconazole, in Non-Albicans Candida Species

Andrea Giammarino1, Chiara Lambona2, Alessia Raucci2

  • 1Department of Public Health and Infectious Diseases, Sapienza University of Rome, Rome, Italy.

Microbiologyopen
|July 8, 2026
PubMed

Insights

Novel antifungal therapies are crucial due to rising drug resistance in Candida infections. Combining Fluconazole with HDAC6/8 inhibitor MC1568 shows promise, reducing biofilms and enhancing efficacy against non-albicans Candida species.

Area of Science:

  • Mycology
  • Pharmacology
  • Infectious Diseases

Background:

  • Fungal infections, especially candidemia, are a significant health threat, particularly for immunocompromised patients.
  • Non-albicans Candida (NAC) species increasingly cause infections, with rising resistance to existing antifungal drugs like azoles and echinocandins.
  • There is an urgent need for new antifungal strategies to overcome drug resistance.

Purpose of the Study:

  • To evaluate the antifungal efficacy of clinically approved histone deacetylase inhibitors (HDACi) and a selective HDAC6/8 inhibitor (MC1568).
  • To assess the combination therapy of MC1568 with Fluconazole against NAC species.
  • To determine the in vivo efficacy and in vitro toxicity of the MC1568/Fluconazole combination.

Main Methods:

  • Screening of Vorinostat, Romidepsin, Tucidinostat, and MC1568 alone and with Fluconazole.
  • Assessing biofilm formation and antifungal activity against NAC species.
  • Evaluating efficacy in Galleria mellonella infection models and toxicity in human retinal pigment epithelium (RPE) cells.

Main Results:

  • The combination of Fluconazole and MC1568 demonstrated significant synergistic antifungal effects.
  • This combination effectively reduced biofilm formation and enhanced activity against Candida guillermondii, Candida lusitaniae, and Candida tropicalis.
  • In vivo studies showed a 70% increase in survival rates against Candida tropicalis infections in Galleria mellonella larvae, with low toxicity observed in RPE cells.

Conclusions:

  • The HDAC6/8 inhibitor MC1568, in combination with Fluconazole, shows significant potential as an adjunct therapy against NAC infections.
  • This combination effectively combats biofilm formation and enhances antifungal activity.
  • Further research is warranted to optimize this combination for clinical application against resistant fungal pathogens.
Keywords:
Candida sppGalleria mellonella modeladherencebiofilmdrug combinationhistone deacetylaseslysine deacetylation

More Related Videos

An Ex vivo Assay to Study Candida albicans Hyphal Morphogenesis in the Gastrointestinal Tract07:42

An Ex vivo Assay to Study Candida albicans Hyphal Morphogenesis in the Gastrointestinal Tract

Published on: July 1, 2020

Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis08:48

Bio-energetics Investigation of Candida albicans Using Real-time Extracellular Flux Analysis

Published on: March 19, 2019

Related Concept Videos

Candidiasis01:20

Candidiasis

Candidiasis is a fungal infection caused by opportunistic species of Candida. It can affect various anatomical sites, including the skin, oral cavity, nails, and genitourinary tract. Among its forms, vaginal candidiasis is the most common type of mucosal infection. It typically results from the overgrowth of Candida albicans in the vaginal mucosa. Under normal conditions, C. albicans exists as a commensal organism within the vaginal microbiota, regulated by the dominance of lactobacilli, which...
Antifungal Agents01:15

Antifungal Agents

Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...
Cryptococcal Meningitis01:27

Cryptococcal Meningitis

Cryptococcal meningitis is a life-threatening opportunistic infection predominantly associated with HIV/AIDS, accounting for over 100,000 deaths annually worldwide. However, it also affects individuals with other forms of immunosuppression, including those undergoing immunosuppressive therapy, organ transplant recipients, patients with innate immunodeficiencies, and individuals with hematological disorders. The infection is caused mainly by Cryptococcus neoformans and Cryptococcus gattii,...