Aspergillus fumigatus conidial pigment and cAMP signal transduction: significance for virulence.
The conidial pigment of Aspergillus fumigatus contains 1,8-dihydroxynaphthalene (DHN)-like pentaketide melanin. It plays a major role in the protection of the fungus against immune effector cells; for example, it is able to scavenge reactive oxygen species generated by alveolar macrophages and neutrophiles. The polyketide synthase PKSP (ALB1) is a key-enzyme of the biosynthesis pathway; its structural gene is part of a gene cluster. Furthermore, the presence of a functional pksP (albl) gene in A. fumigatus conidia is associated with an inhibition of phagolysosome fusion in human monocyte-derived macrophages. Moreover, the analysis of mutants that are defective in elements of the cAMP signaling pathway found that they are almost avirulent in an optimized low dose murine inhalation model. Taken together, our results indicate that the cAMP/PKA signal transduction pathway is required for A. fumigatus pathogenicity. In addition, we showed that the expression of the pksP gene is, at least in part, controlled by the cAMP/ PKA signal transduction pathway. Currently, we hypothesize that pentaketide melanin is important for defence against ROS. However, besides its contribution to the biosynthesis of DHN-like melanin, PKSP also appears to be involved in the formation of another compound which is immunosuppressive.
Brakhage
A A
AA
Leibniz-lnstitute for Natural Products Research and Infection Biology-Hans-Knoell-lnstitute, Department of Molecular and Applied Microbiology, Jena, Germany. Axel.Brakhage@HKI-Jena.de
Liebmann
B
B
D000818:Animals; D001232:Aspergillus fumigatus / Q000254:growth & development / Q000378:metabolism / Q000472:pathogenicity*; D000242:Cyclic AMP / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008543:Melanins / Q000378:metabolism*; D051379:Mice; D009284:Naphthols / Q000378:metabolism*; D010860:Pigments, Biological / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D014774:Virulence
C423455:1,8-dihydroxynaphthalene melanin; D005656:Fungal Proteins; D008543:Melanins; D009284:Naphthols; D010860:Pigments, Biological; D000242:Cyclic AMP