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Front. Microbiol. | doi: 10.3389/fmicb.2019.02573

Fungal Cell Wall: Emerging Antifungals and Drug Resistance

 Soraia L. Lima1, Arnaldo L. Colombo1 and  João N. de Almeida Júnior2*
  • 1Federal University of São Paulo, Brazil
  • 2Clinical Hospital, Faculty of Medicine, University of São Paulo, Brazil

The cell wall is an essential component in fungal homeostasis. The lack of a covering wall in human cells make 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 in vitro activity against the multidrug resistant species Candida auris, Fusarium solani and Lomentospora prolificans. The alternative carbon sources in the infection site changes the cell wall β-D-glucan and chitin composition, leading to echinocandin and amphotericin resistance. Candida populations that survive echinocandin exposure develop tolerance and show high chitin content in the cell wall, whilst fungal species such as Aspergillus flavus 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.

Keywords: antifungals, therapy, Resistance, Fungi, Cell Wall

Received: 19 Aug 2019; Accepted: 23 Oct 2019.

Copyright: © 2019 Lima, Colombo and de Almeida Júnior. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. João N. de Almeida Júnior, Clinical Hospital, Faculty of Medicine, University of São Paulo, São Paulo, Brazil, jnaj99@gmail.com