Functional analysis of the superoxide dismutase family in Aspergillus fumigatus

Abstract

SummaryReactive oxidant species produced by phagocytes have been reported as being involved in the killing of Aspergillus fumigatus. Fungal superoxide dismutases (SODs) that detoxify superoxide anions could be putative virulence factors for this opportunistic pathogen. Four genes encoding putative Sods have been identified in the A. fumigatus genome: a cytoplasmic Cu/ZnSOD (AfSod1p), a mitochondrial MnSOD (AfSod2p), a cytoplasmic MnSOD (AfSod3p) and AfSod4 displaying a MnSOD C-terminal domain. During growth, AfSOD1 and AfSOD2 were highly expressed in conidia whereas AfSOD3 was only strongly expressed in mycelium. AfSOD4 was weakly expressed compared with other SODs. The deletion of AfSOD4 was lethal. Dsod1 and Dsod2 mutants showed a growth inhibition at high temperature and a hypersensitivity to menadione whereas the sod3 mutant had only a slight growth delay at high temperature. Multiple mutations had only an additive effect on the phenotype. The triple sod1/sod2/sod3 mutant was characterized by a delay in conidial germination, a reduced conidial survival during storage overtime, the highest sensitivity to menadione and an increased sensitivity to killing by alveolar macrophage of immunocompetent mice. In spite of these phenotypes, no significant virulence difference was observed between the triple mutant and parental strain in experimental murine aspergillosis models in immunocompromised animals.

Fungal antioxidant pathways promote survival against neutrophils during infection

“…In this study, we identified a role for the superoxide dismutases in mediating hyphal survival during oxidation by neutrophils and during infection. Our findings are consistent with increased cytoplasmic SOD1 and SOD3 but not mitochondrial SOD2 expression by A. fumigatus hyphae in the presence of normal versus CGD neutrophils (72) and the increased susceptibility of A. fumigatus Δsod1/2/3 mutants to killing by alveolar macrophages (37). However, Δsod1/2/3 mutants showed no difference in survival in an immunocompromised lung infection model (37).…”

“…Figure 10 also illustrates that A. fumigatus produces 3 superoxide dismutases that catalyze the conversion of superoxide to H 2 O 2 (37,38). SOD1 and SOD3 are both cytoplasmic, whereas SOD2 is restricted to the mitochondrial membrane (37). In this study, we identified a role for the superoxide dismutases in mediating hyphal survival during oxidation by neutrophils and during infection.…”

“…Further, we found that topical application of PX-12 was sufficient to restrict fungal growth in vivo, thereby indicating that this or similar compounds that target the thioredoxin pathway can block fungal thioredoxins and inhibit the predominant antioxidant defense utilized by these pathogens during infection. Figure 10 also illustrates that A. fumigatus produces 3 superoxide dismutases that catalyze the conversion of superoxide to H 2 O 2 (37,38). SOD1 and SOD3 are both cytoplasmic, whereas SOD2 is restricted to the mitochondrial membrane (37).…”

Biochemical and Molecular Analysis of Superoxide Dismutase in Sordaria fimicola and Aspergillus niger Collected from Different Environments

“…The Cu/Zn (SOD) gene from Cordeceps militaris with a deduced 154 amino acids that shows 72-95% sequence similarities to Cu/Zn (SOD) from other fungi has been described earlier [24]. Four SOD genes in the genome of the A. fumigates have been reported and proteins of these genes provide protection to the organisms against oxidative stress [25]. PTMs are means of important mechanisms for the proper functioning of proteins [26].…”

Phylogenetic and Functional Analysis of Aspergillus fumigatus MGTC, a Fungal Protein Homologous to a Bacterial Virulence Factor

“…The role of AfuMGTC in A. fumigatus pathogenicity was investigated as described previously by Lambou et al (18). No significant difference was seen in the survival rates of cohorts of 10 mice infected intranasally at 10 5 conidia/mouse with the parental strain, the mgtc mutant, and the complemented mgtc mutant strain.…”