VIRULENCE OF CATALASE-DEFICIENT ASPERGILLUS-NIDULANS IN P47(PHOX- -) MICE - IMPLICATIONS FOR FUNGAL PATHOGENICITY AND HOST-DEFENSE IN CHRONIC GRANULOMATOUS-DISEASE/
Yc. Chang et al., VIRULENCE OF CATALASE-DEFICIENT ASPERGILLUS-NIDULANS IN P47(PHOX- -) MICE - IMPLICATIONS FOR FUNGAL PATHOGENICITY AND HOST-DEFENSE IN CHRONIC GRANULOMATOUS-DISEASE/, The Journal of clinical investigation, 101(9), 1998, pp. 1843-1850
Chronic granulomatous disease (CGD) is a rare genetic disorder in whic
h phagocytes fail to produce superoxide because of defects in one of s
everal components of the NADPH oxidase complex. As a result, patients
develop recurrent life-threatening bacterial and fungal infections. Th
e organisms to which CGD patients are most susceptible produce catalas
e, regarded as an important factor for microbial pathogenicity in CGD.
To test the role of pathogen-derived catalase in CGD directly, we hav
e generated isogenic strains of Aspergillus nidulans in which one or b
oth of the catalase genes (catA and catB), have been deleted. We hypot
hesized that catalase negative mutants would be less virulent than the
wild-type strain in experimental animal models. CGD mice were produce
d by disruption of the p47(phox) gene which encodes the 47-kD subunit
of the NADPH oxidase. Wild-type A. nidulans inoculated intranasally ca
used fatal infection in CGD mice, but did not cause disease in wild-ty
pe littermates. Surprisingly, wild-type A. nidulans and the catA, catB
, and catA/catB mutants were equally virulent in CGD mice. Histopathol
ogical studies of fatally infected CGD mice showed widely distributed
lesions in the lungs regardless of the presence or absence of the catA
and catB genes. Similar to the CGD model, catalase-deficient A. nidul
ans was highly virulent in cortisone-treated BALB/c mice. Taken togeth
er, these results indicate that catalases do not play a significant ro
le in pathogenicity of A. nidulans in p47(phox-/-) mice, and therefore
raise doubt about the central role of catalases as a fungal virulence
factor in CGD.