TY - JOUR
T1 - Cryptococcal therapies and drug targets
T2 - the old, the new and the promising
AU - Coelho, Carolina
AU - Casadevall, Arturo
N1 - Publisher Copyright:
© 2016 John Wiley & Sons Ltd
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
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U2 - 10.1111/cmi.12590
DO - 10.1111/cmi.12590
M3 - Review article
C2 - 26990050
AN - SCOPUS:84962845339
SN - 1462-5814
VL - 18
SP - 792
EP - 799
JO - Cellular microbiology
JF - Cellular microbiology
IS - 6
ER -