ISOLATION AND CHARACTERIZATION OF A PIGMENTLESS-CONIDIUM MUTANT OF ASPERGILLUS-FUMIGATUS WITH ALTERED CONIDIAL SURFACE AND REDUCED VIRULENCE

Aspergillus fumigatus is an important pathogen of immunocompromised ho sts, causing pneumonia and invasive disseminated disease with high mor tality, The factors contributing to the predominance of A. fumigatus a s an opportunistic pathogen are largely unknown, Since the survival of conidia in the host is a prerequisite for establishing disease, we ha ve been attempting to identify factors which are associated with conid ia and, simultaneously, important for infection. Therefore, an A. fumi gatus mutant strain (white [W]) lacking conidial pigmentation was isol ated, Scanning electron microscopy revealed that conidia of the W muta nt also differed in their surface morphology from those of the wild ty pe (WT). Mutant (W) and WT conidia were compared with respect to their capacities to stimulate an oxidative response in human phagocytes, th eir intracellular survival in human monocytes, and virulence in a muri ne animal model, Luminol-dependent chemiluminescence was Ill-fold high er when human neutrophils or monocytes were challenged with W conidia compared with NT conidia. Furthermore, mutant conidia were more suscep tible to killing by oxidants in vitro and were more efficiently damage d by human monocytes in vitro than WT conidia. In a murine animal mode l, the W mutant strain showed reduced virulence compared with the WT, A reversion analysis of the W mutant demonstrated that all phenotypes associated with the W mutant, i.e., altered conidial surface, amount o f reactive oxygen species release, susceptibility to hydrogen peroxide , and reduced virulence in an murine animal model, coreverted in rever tants which had regained the ability to produce green spores. This fin ding strongly suggests that the A. fumigatus mutant described here car ries a single mutation which caused all of the observed phenotypes, Ou r results suggest that the conidium pigment or a structural feature re lated to it contributes to fungal resistance against host defense mech anisms in A. fumigatus infections.