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

Author(s)

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.

• Document type: Review article
• Source: FRONTIERS IN MICROBIOLOGY; v. 8, JAN 23 2017.
• Web of Science Citations: 66

Abstract

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)

• FAPESP's process: 16/17048-4 - Two-component signal transduction (TCST) system as a new target for the treatment of paracoccidioidomycosis
• Grantee: Caroline Maria Marcos
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 15/14023-8 - Use of peptides with anti-adhesive activity in Paracoccidoides spp. in the treatment and prophylaxis of the paracoccidioidomycosis
• Grantee: Haroldo Cesar de Oliveira
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 13/10917-9 - Alternative animal models: Virulence of different phylogenetic species of Paracoccidioides and effect of the 30kDa 43kDa protein and their antibodies
• Grantee: Liliana Scorzoni
• Support type: Scholarships in Brazil - Post-Doctorate
• FAPESP's process: 15/03700-9 - Alternative animal as a model to study Paracoccidioides- host interaction: virulence, efficacy and toxicology of antifungal compounds and new preventive treatments
• Grantee: Maria José Soares Mendes Giannini
• Support type: Regular Research Grants