Aspergillus fumigatus MADS-Box Transcription Factor rlmA Is Required for Regulation of the Cell Wall Integrity and Virulence. Issue 9 (1st September 2016)

• Record Type: Journal Article
• Authors: Rocha, Marina Campos; Fabri, João Henrique Tadini Marilhano; Franco de Godoy, Krissia; Alves de Castro, Patrícia; Hori, Juliana Issa; Ferreira da Cunha, Anderson; Arentshorst, Mark; Ram, Arthur F J; van den Hondel, Cees A M J J; Goldman, Gustavo Henrique; Malavazi, Iran
• Is Part Of: G3. Volume 6:Issue 9(2016)
• Page Start: 2983
• Page End: 3002
• Publication Date: 2016-09-01
• Subjects: Aspergillus fumigatus -- rlmA -- cell wall integrity -- virulence -- mpkA; Genetics -- Research -- Periodicals; Genomics -- Periodicals; Genetics; Genomics; Genes; Genetics -- Research; Genomics; Electronic journals; Periodical; Periodicals; Fulltext; Internet Resources; Periodicals; 572.8
• DOI: 10.1534/g3.116.031112
• Languages: English
• ISSNs: 2160-1836

Abstract

Abstract: The Cell Wall Integrity (CWI) pathway is the primary signaling cascade that controls the de novo synthesis of the fungal cell wall, and in Saccharomyces cerevisiae this event is highly dependent on the RLM1 transcription factor. Here, we investigated the function of RlmA in the fungal pathogen Aspergillus fumigatus . We show that the Δ rlmA strain exhibits an altered cell wall organization in addition to defects related to vegetative growth and tolerance to cell wall-perturbing agents. A genetic analysis indicated that rlmA is positioned downstream of the pkcA and mpkA genes in the CWI pathway. As a consequence, rlmA loss-of-function leads to the altered expression of genes encoding cell wall-related proteins. RlmA positively regulates the phosphorylation of MpkA and is induced at both protein and transcriptional levels during cell wall stress. The rlmA was also involved in tolerance to oxidative damage and transcriptional regulation of genes related to oxidative stress adaptation. Moreover, the Δ rlmA strain had attenuated virulence in a neutropenic murine model of invasive pulmonary aspergillosis. Our results suggest that RlmA functions as a transcription factor in the A. fumigatus CWI pathway, acting downstream of PkcA-MpkA signaling and contributing to the virulence of this fungus.