Catalases of Aspergillus fumigatus and inflammation in aspergillosis

Abstract

The article describs various features of aspergillosis and a discussed the role of calatases produced by Aspergillus fumigatus during infection. Since a large body of invasive Aspergillus infection occurs as an opportunistic infection in variously impaired defense mechanisms, there is a wide spectrum of histopathological features of lesions demonstrated at the site of infection. Accordingly, histopathology of the lesions can be understood as a phenotypical representation of interaction between differently impaired functions of neutrophils and macrophages and virulence factors of invading Aspergilli. Consideration of previous pathological knowledge regarding infection and inflammation provides much important information to predict the pathophysiology of a patient. Meanwhile, detoxification of hydrogen peroxide by catalases has been proposed as a way to overcome this host response. A. fumigatus produces three active catalases, one from conidia and two from mycelia. CatAp, a spore specific monofunctional catalase, is resistant to heat and metal ions. In spite of their increased sensitivity to H2O2, killing of catA conidia by alveolar macrophages, virulence in animals was similar to wild type conidia. In contrast to mycelial Cat1p, and CatAp catalases, the mycelial Cat2p is a bifunctional catalase-peroxidase enzyme and is also sensitive to heat, metal ions and detergent. Surprisingly, the mycelium of the double cat1 cat2 mutant with no catalase activity has only a slightly increased sensitivity to H2O2 and was as sensitive to the killing of polymorphonuclear neutrophils as the wild type strain. However, it showed a delayed infection in the rat model of aspergillosis compared to the wild type strain. Consequently, it should be emphasized that conidial catalase is not a virulence factor but that mycelial catalases transiently protect the fungus from the host defence reactions.