The cell wall integrity pathway contributes to the early stages of Aspergillus fumigatus asexual development.

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The cell wall integrity pathway contributes to the early stages of Aspergillus fumigatus asexual development.

Appl Environ Microbiol. 2020 Jan 31;:

Authors: Rocha MC, Fabri JHTM, Simões IT, Silva-Rocha R, Hagiwara D, da Cunha AF, Goldman GH, Cánovas D, Malavazi I

Aspergillus fumigatus is a major cause of human disease. The survival of this fungus is dependent on 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 fungal-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 are currently unknown. Here, we investigated the role of CWIP in conidiation. We show that mutants in the CWIP pkcA G579R, ΔmpkA and ΔrlmA displayed reduced conidiation during synchronized asexual differentiation. The transcription factor RlmA directly regulated the expression of regulators of conidiation, including flbB, flbC, brlA, 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 RlmA and MpkA were increased during asexual differentiation. We also observed that MpkA physically associated with the proteins FlbB, FlbC, BrlA 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 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 RlmA 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.

PMID: 32005734 [PubMed – as supplied by publisher]

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