Antifungal Therapy: New Advances in the Understanding and Treatment of Mycosis

Autor(es)

Scorzoni, Liliana ; de Paula e Silva, Ana C. A. ; Marcos, Caroline M. ; Assato, Patricia A. ; de Melo, Wanessa C. M. A. ; de Oliveira, Haroldo C. ; Costa-Orlandi, Caroline B. ; Mendes-Giannini, Maria J. S. ; Fusco-Almeida, Ana M.

• Tipo de documento: Artigo de Revisão
• Fonte: FRONTIERS IN MICROBIOLOGY; v. 8, JAN 23 2017.
• Citações Web of Science: 66

Resumo

The high rates of morbidity and mortality caused by fungal infections are associated with the current limited antifungal arsenal and the high toxicity of the compounds. Additionally, identifying novel drug targets is challenging because there are many similarities between fungal and human cells. The most common antifungal targets include fungal RNA synthesis and cell wall and membrane components, though new antifungal targets are being investigated. Nonetheless, fungi have developed resistance mechanisms, such as overexpression of efflux pump proteins and biofilm formation, emphasizing the importance of understanding these mechanisms. To address these problems, different approaches to preventing and treating fungal diseases are described in this review, with a focus on the resistance mechanisms of fungi, with the goal of developing efficient strategies to overcoming and preventing resistance as well as new advances in antifungal therapy. Due to the limited antifungal arsenal, researchers have sought to improve treatment via different approaches, and the synergistic effect obtained by the combination of antifungals contributes to reducing toxicity and could be an alternative for treatment. Another important issue is the development of new formulations for antifungal agents, and interest in nanoparticles as new types of carriers of antifungal drugs has increased. In addition, modifications to the chemical structures of traditional antifungals have improved their activity and pharmacokinetic parameters. Moreover, a different approach to preventing and treating fungal diseases is immunotherapy, which involves different mechanisms, such as vaccines, activation of the immune response and inducing the production of host antimicrobial molecules. Finally, the use of a mini-host has been encouraging for in vivo testing because these animal models demonstrate a good correlation with the mammalian model; they also increase the speediness of as well as facilitate the preliminary testing of new antifungal agents. In general, many years are required from discovery of a new antifungal to clinical use. However, the development of new antifungal strategies will reduce the therapeutic time and/or increase the quality of life of patients. (AU)

• Processo FAPESP: 15/03700-9 - Animais alternativos aplicados à interação Paracoccidioides-hospedeiro para o desenvolvimento de estudos de virulência, eficácia e toxicidade de compostos antifúngicos e tratamentos preventivos
• Beneficiário: Maria José Soares Mendes Giannini
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/10917-9 - Modelos animais alternativos: Virulência de diferentes espécies filogenéticas de Paracoccidioides e efeito das proteínas 43kDa e 30kDa e de seus anticorpos
• Beneficiário: Liliana Scorzoni
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 16/17048-4 - Sistema de dois componentes de transdução de sinais (TCST) como novo alvo para o delineamento de peptídeos antifúngicos
• Beneficiário: Caroline Maria Marcos
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/14023-8 - Uso de peptídeos com atividade anti-adesiva em Paracoccidoides spp. na terapêutica e profilaxia da paracoccidioidomicose
• Beneficiário: Haroldo Cesar de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado