Cell wall integrity M AP kinase signalling pathway in the human-pathogenic fungus Aspergillus fumigatus

Radhika Jain 1,2*, Vito Valiante 1, Thorsten Heinekamp 1, Axel.A.Brakhage 1,2.

Author address: 

1Leibniz Institute for Natural Product Research and Infection Biology - HKI, Jena, Germany. 2University of Jena, Germany.

Abstract: 

Mitogen-activated protein kinase (M APK) cascades are evolutionary conserved signalling modules transducing stimuli from the cell surface to the nucleus. MAPK pathways control key virulence functions and are involved in the regulation of various cellular responses in eukaryotes. In A. fumigatus, three putative MAP kinases are involved in the cell wall integrity (CW I) signalling pathway: bck1 (MAPK kinase kinase), mkk2 (MAPK kinase) and mpkA (MAPK).To investigate whether bck1, mkk2 and mpkA are involved in CW I signalling of A. fumigatus, mutant strains of respective genes were constructed and phenotypically analysed. In addition, transcriptional regulation of mpkA, and the function of the corresponding protein was studied. An A. fumigatus strain was generated carrying the lacZ-reporter gene fused to the mpkA-promoter. Post transcriptional modification of MpkA was monitored by western blot analysis.Functional analysis of Bck1, Mkk2 and MpkA in A. fumigatus revealed their involvement in hyphal growth and filamentation. The sensitivity of these mutants against cell wall inhibitors demonstrates that the genes are acting in the CW I signalling pathway and mediate cell wall damage responses. Furthermore, new insights into the regulation of MAPK signalling in A. fumigatus were gained. It was observed that mpkA is regulated transcriptionally in response to cell wall disrupting agents. By contrast, regulation of MpkA following treatment with oxidative stress agents occurs at the post transcriptional level. Interestingly, delta mpkA mutants are still virulent in a mouse infection model. *Student poster
2009

abstract No: 

39

Full conference title: 

6th International Aspergillus Meeting
    • Asperfest 6 (2009)