title: Cryptococcal therapies and drug targets: the old, the new and the promising.
abstract: Half a century after the introduction of Amphotericin B the management of cryptococcosis remains unsatisfactory. The disease, caused primarily by the two fungal species Cryptococcus neoformans and Cryptococcus gattii, remains responsible for considerable morbidity and mortality despite standard medical care. Current therapeutic options are limited to Amphotericin B, azoles and 5-flucytosine. However, this organism has numerous well-characterized virulence mechanisms that are amenable to pharmacological interference and are thus potential therapeutic targets. Here, we discuss existing approved antifungal drugs, resistance mechanisms to these drugs and non-standard antifungal drugs that have potential in treatment of cryptococcosis, including immunomodulatory strategies that synergize with antifungal drugs, such as cytokine administration or monoclonal antibodies. Finally, we summarize attempts to target well-described virulence factors of Cryptococcus, the capsule or fungal melanin. This review emphasizes the pressing need for new therapeutic alternatives for cryptococcosis.
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Carolina
authors.identifier: 0000-0002-7523-3031
authors.initials: C
authors.lastname: Coelho
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D060085:Coinfection / Q000188:drug therapy; D003453:Cryptococcosis / Q000188:drug therapy* / Q000382:microbiology; D056285:Cryptococcus gattii / Q000187:drug effects / Q000472:pathogenicity; D003455:Cryptococcus neoformans / Q000472:pathogenicity; D025141:Drug Resistance, Fungal / Q000187:drug effects*; D015658:HIV Infections; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D042845:Laccase / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods
chemical_list: D000935:Antifungal Agents; D007155:Immunologic Factors; D008543:Melanins; D042845:Laccase