The importance of connections between the cell wall integrity pathway and the unfolded protein response in filamentous fungi

Malavazi, Iran
Goldman, Gustavo Henrique
Brown, Neil Andrew

Corresponding author. Neil Andrew Brown, Department of Pharmaceutical Sciences - Ribeirão Preto, University of São Paulo (USP), Avenida do Café S/N, Monte Alegre, CEP 14040-903, Ribeirão Preto - SP, Brazil. Tel.: +55 16 36024311; E-mail: [email protected]

Iran Malavazi is an Associate Professor and Young Investigator at the Universidade Federal de São Carlos, São Carlos, Brazil. His main research interest is the study of the molecular determinant of pathogenicity in Aspergillus fumigatus.

Gustavo Henrique Goldman is a Professor of Molecular Biology and Genetics at the University of São Paulo - Ribeirão Preto, Brazil. His research interests include medical and industrial mycology.

Neil Andrew Brown is a Postdoctoral fellow at the University of São Paulo - Ribeirão Preto, Brazil. His research focuses on fungal pathogenicity and the utilization of fungi for biofuel production.

Briefings in Functional Genomics 13(6):p 456-470, November 2014. | DOI: 10.1093/bfgp/elu027

In the external environment, or within a host organism, filamentous fungi experience sudden changes in nutrient availability, osmolality, pH, temperature and the exposure to toxic compounds. The fungal cell wall represents the first line of defense, while also performing essential roles in morphology, development and virulence. A polarized secretion system is paramount for cell wall biosynthesis, filamentous growth, nutrient acquisition and interactions with the environment. The unique ability of filamentous fungi to secrete has resulted in their industrial adoption as fungal cell factories. Protein maturation and secretion commences in the endoplasmic reticulum (ER). The unfolded protein response (UPR) maintains ER functionality during exposure to secretion and cell wall stress. UPR, therefore, influences secretion and cell wall homeostasis, which in turn impacts upon numerous fungal traits important to pathogenesis and biotechnology. Subsequently, this review describes the relevance of the cell wall and UPR systems to filamentous fungal pathogens or industrial microbes and then highlights interconnections between the two systems. Ultimately, the possible biotechnological applications of an enhanced understanding of such regulatory systems in combating fungal disease, or the removal of natural bottlenecks in protein secretion in an industrial setting, are discussed.