The Cell Wall Integrity Pathway Contributes to the Early Stages of Aspergillus fumigatus Asexual Development

Author(s)

Rocha, Marina Campos ^[1] ; Tadini Marilhano Fabri, Joao Henrique ^[1] ; Simoes, Isabelle Taira ^[1] ; Silva-Rocha, Rafael ^[2] ; Hagiwara, Daisuke ^[3] ; da Cunha, Anderson Ferreira ^[1] ; Goldman, Gustavo Henrique ^[4] ; Canovas, David ^[5] ; Malavazi, Iran ^[1]

Affiliation

^[1] Univ Fed Sao Carlos, Ctr Ciencias Biol & Saude, Dept Genet & Evolucao, Sao Carlos, SP - Brazil

^[2] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol, Ribeirao Preto, SP - Brazil

^[3] Univ Tsukuba, Fac Life & Environm Sci, Ibaraki - Japan

^[4] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Dept Ciencias Farmaceut, Ribeirao Preto, SP - Brazil

^[5] Univ Seville, Dept Genet, Seville - Spain

• Document type: Journal article
• Source: Applied and Environmental Microbiology; v. 86, n. 7 APR 2020.
• Web of Science Citations: 0

Abstract

Aspergillus fumigatus is a major cause of human disease. The survival of this fungus is dependent on the cell wall organization and function of its components. The cell wall integrity pathway (CWIP) is the primary signaling cascade that controls de novo synthesis of the cell wall in fungi. Abundant conidiation is a hallmark in A. fumigatus, and uptake of conidia by a susceptible host is usually the initial event in infection. The formation of conidia is mediated by the development of fungus-specific specialized structures, conidiophores, which are accompanied by cell wall remodeling. The molecular regulation of these changes in cell wall composition required for the rise of conidiophore from the solid surface and to disperse the conidia into the air is currently unknown. Here, we investigated the role of CWIP in conidiation. We show that CWIP pkcA(G)(579R), Delta mpkA, and Delta rlmA mutants displayed reduced conidiation during synchronized asexual differentiation. The transcription factor RImA directly regulated the expression of regulators of conidiation, including flbB, flbC, abaA, and rasB, as well as genes involved in cell wall synthesis and remodeling, and this affected the chitin content in aerial hyphae. Phosphorylation of RImA and MpkA was increased during asexual differentiation. We also observed that MpkA physically associated with the proteins FIbB, FlbC, BrIA, and RasB during this process, suggesting another level of cross talk between the CWIP and asexual development pathways. In summary, our results support the conclusion that one function of the CWIP is the regulation of asexual development in filamentous fungi. IMPORTANCE A remarkable feature of the human pathogen Aspergillus fumigatus is its ability to produce impressive amounts of infectious propagules known as conidia. These particles reach immunocompromised patients and may initiate a life-threatening mycosis. The conidiation process in Aspergillus is governed by a sequence of proteins that coordinate the development of conidiophores. This process requires the remodeling of the cell wall so that the conidiophores can rise and withstand the chains of conidia. The events regulating cell wall remodeling during conidiation are currently unknown. Here, we show that the cell wall integrity pathway (CWIP) components RImA and MpkA directly contribute to the activation of the conidiation cascade by enabling transcription or phosphorylation of critical proteins involved in asexual development. This study points to an essential role for the CWIP during conidiation and provides further insights into the complex regulation of asexual development in filamentous fungi. (AU)

• 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: 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: 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