AUTHOR=Lima Soraia L. , Colombo Arnaldo L. , de Almeida Junior João N. 

TITLE=Fungal Cell Wall: Emerging Antifungals and Drug Resistance

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.02573

DOI=10.3389/fmicb.2019.02573

ISSN=1664-302X

ABSTRACT=<p>The cell wall is an essential component in fungal homeostasis. The lack of a covering wall in human cells makes this component an attractive target for antifungal development. The host environment and antifungal stress can lead to cell wall modifications related to drug resistance. Antifungals targeting the cell wall including the new β-D-glucan synthase inhibitor ibrexafungerp and glycosyl-phosphatidyl Inositol (GPI) anchor pathway inhibitor fosmanogepix are promising weapons against antifungal resistance. The fosmanogepix shows strong <italic>in vitro</italic> activity against the multidrug-resistant species <italic>Candida auris</italic>, <italic>Fusarium solani</italic>, and <italic>Lomentospora prolificans.</italic> The alternative carbon sources in the infection site change the cell wall β-D-glucan and chitin composition, leading to echinocandin and amphotericin resistance. <italic>Candida</italic> populations that survive echinocandin exposure develop tolerance and show high chitin content in the cell wall, while fungal species such as <italic>Aspergillus flavus</italic> with a higher β-D-glucan content may show amphotericin resistance. Therefore understanding fungal cell dynamics has become important not only for host-fungal interactions, but also treatment of fungal infections. This review summarizes recent findings regarding antifungal therapy and development of resistance related to the fungal cell wall of the most relevant human pathogenic species.</p>