AfMkk2 is required for cell wall integrity signaling, adhesion, and full virulence of the human pathogen Aspergillus fumigatus.
The cell wall integrity (CWI) pathway, best characterized in S. cerevisiae, is strikingly conserved in Aspergillus species. We analyzed the importance of AfMkk2, a CWI signaling kinase, for virulence and antifungal therapy in the human pathogen A. fumigatus. A mutant lacking AfMkk2 is less adherent to glass and plastic surfaces and shows increased sensitivity to alkaline pH stress and antifungals. Rather than AfMpkA, the target kinase of AfMkk2, AfMpkB is activated in the mutant under cell wall stress. Interestingly, the mutant lacking AfMkk2 shows an enhanced sensitivity to posaconazole and voriconazole. And in agreement with its sensitivity to moderate temperatures, it is less virulent in a murine infection model. Our data underline the importance of mkk2 for the fitness, but also for the pathogenicity of A. fumigatus.
Dirr
Franziska
F
Max von Pettenkofer-Institut, Ludwig-Maximilians-Universität, Pettenkoferstraße 9a, 80336 Munich, Germany.
Echtenacher
Bernd
B
Heesemann
Jürgen
J
Hoffmann
Petra
P
Ebel
Frank
F
Wagener
Johannes
J
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D001228:Aspergillosis / Q000382:microbiology / Q000401:mortality; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity*; D002448:Cell Adhesion; D002473:Cell Wall / Q000502:physiology*; D004195:Disease Models, Animal; D005898:Glass; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000172:deficiency / Q000378:metabolism*; D010969:Plastics; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction; D016019:Survival Analysis; D013696:Temperature; D014230:Triazoles / Q000494:pharmacology; D014774:Virulence; D037521:Virulence Factors / Q000172:deficiency / Q000378:metabolism*; D065819:Voriconazole
D000935:Antifungal Agents; D010969:Plastics; D011743:Pyrimidines; D014230:Triazoles; D037521:Virulence Factors; C101425:posaconazole; D020929:Mitogen-Activated Protein Kinase Kinases; D065819:Voriconazole