Histone deacetylases and their inhibition in $Candida$ species
Résumé
Fungi are generally benign members of the human mucosal flora or live as saprophytes
in the environment. However, they can become pathogenic, leading to invasive and
life threatening infections in vulnerable patients. These invasive fungal infections are
regarded as a major public health problem on a similar scale to tuberculosis or malaria.
Current treatment for these infections is based on only four available drug classes.
This limited therapeutic arsenal and the emergence of drug-resistant strains are a
matter of concern due to the growing number of patients to be treated, and new
therapeutic strategies are urgently needed. Adaptation of fungi to drug pressure involves
transcriptional regulation, in which chromatin dynamics and histone modifications play
a major role. Histone deacetylases (HDACs) remove acetyl groups from histones and
actively participate in controlling stress responses. HDAC inhibition has been shown to
limit fungal development, virulence, biofilm formation, and dissemination in the infected
host, while also improving the efficacy of existing antifungal drugs toward Candida spp.
In this article, we review the functional roles of HDACs and the biological effects of HDAC
inhibitors on Candida spp., highlighting the correlations between their pathogenic effects
in vitro and in vivo. We focus on how HDAC inhibitors could be used to treat invasive
candidiasis while also reviewing recent developments in their clinical evaluation.
Domaines
Mycologie| Origine | Fichiers éditeurs autorisés sur une archive ouverte |
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