ChIP‐seq reveals a role for CrzA in the Aspergillus fumigatus high‐osmolarity glycerol response (HOG) signalling pathway. Issue 3 (30th September 2014)

• Record Type: Journal Article
• Authors: de Castro, Patrícia A.; Chen, Chenxi; de Almeida, Ricardo Sérgio Couto; Freitas, Fernanda Z.; Bertolini, Maria C.; Morais, Enyara Rezende; Brown, Neil Andrew; Ramalho, Leandra Naira Zambelli; Hagiwara, Daisuke; Mitchell, Thomas K.; Goldman, Gustavo H.
• Is Part Of: Molecular microbiology. Volume 94:Issue 3(2014)
• Page Start: 655
• Page End: 674
• Publication Date: 2014-09-30
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.12785
• Languages: English
• ISSNs: 0950-382X

Abstract

<abstract abstract-type="main"> <title>Summary</title> <p> <italic>A</italic> <italic>spergillus fumigatus</italic> is an opportunistic pathogen and allergen of mammals. Calcium signalling is essential for <italic>A</italic><italic>. fumigatus</italic> pathogenicity and is regulated by the CrzA transcription factor. We used ChIP‐seq (Chromatin Immunoprecipitation DNA sequencing) to explore CrzA gene targets in <italic>A</italic><italic>. fumigatus</italic>. In total, 165 potential binding peaks including 102 directly regulated genes were identified, resulting in the prediction of the A[GT][CG]CA[AC][AG] CrzA‐binding motif. The 102 CrzA putatively regulated genes exhibited a diverse array of functions. The <italic>phkB</italic> (Afu3g12530) histidine kinase and the <italic>sskB</italic> (Afu1g10940) MAP kinase kinase kinase of the HOG (high‐osmolarity glycerol response) pathway were regulated by CrzA. Several members of the two‐component system (TCS) and the HOG pathway were more sensitive to calcium. CrzA::GFP was translocated to the nucleus upon osmotic stress. CrzA is important for the phosphorylation of the SakA MAPK in response to osmotic shock. The Δ<italic>sskB</italic> was more sensitive to CaCl<sub>2</sub>, NaCl, and paraquat stress, while being avirulent in a murine model of invasive pulmonary aspergillosis. The presence of CaCl<sub>2</sub> and osmotic stresses resulted in synergistic inhibition of Δ<italic>crzA</italic> and Δ<italic>sskB</italic> growth. These results suggest there is a genetic interaction between the <italic>A. fumigatus</italic> calcineurin‐CrzA and HOG pathway that is essential for full virulence.</p> </abstract>