Antifungals discovery: an insight into new strategies to combat antifungal resistance

作者：Alexandre Meneghello Fuentefría, Bruna Pippi, Daiane Flores Dalla Lana, Kelly Donato, Saulo Fernandes de Andrade · 发表于：Letters in Applied Microbiology · 年份：2017 · DOI：10.1111/lam.12820 · 被引用次数：210 · 研究领域：Antifungal resistance and susceptibility、Fungal Infections and Studies、Plant Pathogens and Fungal Diseases

Undeniably, new antifungal treatments are necessary against pathogenic fungi. Fungal infections have significantly increased in recent decades, being highlighted as important causes of morbidity and mortality, particularly in immunocompromised patients. Five main antifungal classes are used: (i) azoles, (ii) echinocandins, (iii) polyenes, (iv) allylamines and (v) pyrimidine analogues. Moreover, the treatment of mycoses has several limitations, such as undesirable side effects, narrow activity spectrum, a small number of targets and fungal resistance, which are still of major concern in clinical practice. The discovery of new antifungals is mostly achieved by the screening of natural or synthetic/semisynthetic chemical compounds. The most recent discoveries in drug resistance mechanism and their avoidance were explored in a review, focusing on different antifungal targets, as well as new agents or strategies, such as combination therapy, that could improve antifungal therapy. SIGNIFICANCE AND IMPACT OF THE STUDY: The failure to respond to antifungal therapy is complex and is associated with microbiological resistance and increased expression of virulence in fungal pathogens. Thus, this review offers an overview of current challenges in the treatment of fungal infections associated with increased antifungal drug resistance and the formation of biofilms in these opportunistic pathogens. Furthermore, the most recent and potential strategies to combat fungal pathogens are explored...