title: Fungistatic activity of all-trans retinoic acid against Aspergillus fumigatus and Candida albicans.
abstract: OBJECTIVE
  Fungal infections are a major complication in hematologic and neoplastic patients causing severe morbidity and mortality. Aspergillus fumigatus and Candida albicans are among the most invasive opportunistic pathogens in immunocompromised patients, and classic antifungal drugs are frequently unsuccessful in these patients. Recent reports hypothesize that the antifungal efficacy of all-trans retinoic acid (ATRA) is mainly related to its strong capacity to stimulate monocyte-mediated immunity, but no consideration was given to its potential direct fungistatic activity. Moreover, ATRA offers the opportunity for systemic therapy.
  
  
  RESULTS
  We investigated the efficacy of ATRA at different concentrations for its antifungal activity against opportunistic A. fumigatus and C. albicans obtained from clinical samples according to standard protocols. A fungistatic activity of ATRA on A. fumigatus and C. albicans at 0.5-1 mM concentration was documented up to 7 days.
  
  
  CONCLUSIONS
  This is the first evidence of a direct and strong fungistatic activity of ATRA against A. fumigatus and C. albicans. The potential adjuvant therapeutic application of ATRA might be useful in the treatment and/or prevention of systemic mycoses in immunocompromised patients. The discovery of a direct fungistatic activity, in association with its reported immunomodulatory properties, makes ATRA an excellent candidate for new combined antifungal strategies for systemic mycoses in immunocompromised and cancer patients.
authors.affiliation: Department of Dermatology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Campione
authors.affiliation: Department of Microbiology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Gaziano
authors.affiliation: Department of Microbiology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Marino
authors.affiliation: Department of Anatomic Pathology, University of Rome Tor Vergata, Rome, Italy.
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001232:Aspergillus fumigatus / Q000187:drug effects*; D002176:Candida albicans / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D014212:Tretinoin
keywords: all-trans retinoic acid; fungal infections; fungistatic activity