Overview of the Interplay Between Cell Wall Integrity Signaling Pathways and Membrane Lipid Biosynthesis in Fungi: Perspectives for Aspergillus fumigatus

Author(s)

Fabri, Joao Henrique T. M. ^[1] ; Rocha, Marina C. ^[1] ; Malavazi, Iran ^[1]

Affiliation

^[1] Univ Fed Sao Carlos, Dept Genet & Evolucao, Sao Carlos - Brazil

• Document type: Review article
• Source: CURRENT PROTEIN & PEPTIDE SCIENCE; v. 21, n. 3, p. 265-283, 2020.
• Web of Science Citations: 1

Abstract

The cell wall (CW) and plasma membrane are fundamental structures that define cell shape and support different cellular functions. In pathogenic fungi, such as Aspegillus fumigatus, they not only play structural roles but are also important for virulence and immune recognition. Both the CW and the plasma membrane remain as attractive drug targets to treat fungal infections, such as the Invasive Pulmonary Aspergillosis (IPA), a disease associated with high morbimortality in immunocompromised individuals. The low efficiency of echinocandins that target the fungal CW biosynthesis, the occurrence of environmental isolates resistant to azoles such as voriconazole and the known drawbacks associated with amphotericin toxicity foster the urgent need for fungal-specific drugable targets and/or more efficient combinatorial therapeutic strategies. Reverse genetic approaches in fungi unveil that perturbations of the CW also render cells with increased susceptibility to membrane disrupting agents and vice-versa. However, how the fungal cells simultaneously cope with perturbation in CW polysaccharides and cell membrane proteins to allow morphogenesis is scarcely known. Here, we focus on current information on how the main signaling pathways that maintain fungal cell wall integrity, such as the Cell Wall Integrity and the High Osmolarity Glycerol pathways, in different species often cross-talk to regulate the synthesis of molecules that comprise the plasma membrane, especially sphingolipids, ergosterol and phospholipids to promote functioning of both structures concomitantly and thus, cell viability. We propose that the conclusions drawn from other organisms are the foundations to point out experimental lines that can be endeavored in A. fumigatus. (AU)

• FAPESP's process: 15/17541-0 - Study of the relationship between genes involved in the cell wall integrity maintenance and thermotolerance in the human pathogenic fungi Aspergillus fumigatus
• Grantee: Iran Malavazi
• Support Opportunities: Regular Research Grants
• FAPESP's process: 16/07870-9 - The influence of mitogen activated protein kinases (MAPK) on the expression of genetic determinants important for Aspergillus fumigatus virulence
• Grantee: Gustavo Henrique Goldman
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/19694-3 - The role of heat shock proteins HsfA and Hsp90 and the regulator SmiA at cell wall integrity pathway activity in the opportunistic human pathogen Aspergillus fumigatus
• Grantee: Iran Malavazi
• Support Opportunities: Regular Research Grants