Enzymatic Mechanisms Involved in Evasion of Fungi to the Oxidative Stress: Focus on Scedosporium apiospermum

Abstract

The airways of patients with cystic fibrosis (CF) are frequently colonized by various filamentous fungi, mainly Aspergillus fumigatus and Scedosporium species. To establish within the respiratory tract and cause an infection, these opportunistic fungi express pathogenic factors allowing adherence to the host tissues, uptake of extracellular iron, or evasion to the host immune response. During the colonization process, inhaled conidia and the subsequent hyphae are exposed to reactive oxygen species (ROS) and reactive nitrogen species (RNS) released by phagocytic cells, which cause in the fungal cells an oxidative stress and a nitrosative stress, respectively. To cope with these constraints, fungal pathogens have developed various mechanisms that protect the fungus against ROS and RNS, including enzymatic antioxidant systems. In this review, we summarize the different works performed on ROS- and RNS-detoxifying enzymes in fungi commonly encountered in the airways of CF patients and highlight their role in pathogenesis of the airway colonization or respiratory infections. The potential of these enzymes as serodiagnostic tools is also emphasized. In addition, taking advantage of the recent availability of the whole genome sequence of S. apiospermum, we identified the various genes encoding ROS- and RNS-detoxifying enzymes, which pave the way for future investigations on the role of these enzymes in pathogenesis of these emerging species since they may constitute new therapeutics targets.

Microglial immune response is impaired against the neurotropic fungusLomentospora prolificans

“…More interestingly, ROS production and phagocytosis dynamics matched each other in J774A.1 cells, suggesting that they are coupled in order to eliminate the fungal threat. In this sense, Scedosporium / Lomentospora species rely on a repertoire of detoxifying enzymes related to oxidative or nitrosative stress, such as catalase or superoxide dismutase (Pellon et al, ; Staerck et al, ), which may be related to fungal survival inside phagolysosomes. Therefore, this suggests that although macrophages and microglia develop oxidative and nitrosative bursts, the fungus may eliminate these toxic molecules efficiently and so overcome immune cell activity.…”

Fungal Respiratory Infections in Cystic Fibrosis (CF): Recent Progress and Future Research Agenda

“…Host response of fungal diseases in CF patients [21] 7. Fungal virulence mechanisms [22][23][24][25][26][27] large study involved 243 CF patients from seven centers in France over a 15-month period. The investigators found that about half of the patients presented with at least one fungal species, while 37% were co-colonized with two species.…”

“…The authors then describe the potential benefits of investigations that seek fungus-specific T cells as diagnostics tools in CF patients [21]. The group led by Fleury details detoxifying enzymes employed by the fungal pathogens in response to reactive-oxygen and -nitrogen species (ROS and RNS) released by the host phagocytic cells [22]. Scedosporium apiospermum genome sequence is the basis of cataloging the 33 genes likely to encode relevant detoxifying enzymes against host ROS and RNS.…”

“…Scedosporium apiospermum genome sequence is the basis of cataloging the 33 genes likely to encode relevant detoxifying enzymes against host ROS and RNS. The domain organizations of superoxide dismutase and catalases genes are summarized [22]. The homologs of these and other related enzymes are also compared for C. albicans, E. dermatitidis and Aspergillus species.…”

“…The homologs of these and other related enzymes are also compared for C. albicans, E. dermatitidis and Aspergillus species. Staerck et al [22] conclude with the description of development of specific immunodiagnostic tool based upon purified catalase of S. boydii [22]. The genetic manipulations of fungal pathogens have yielded valuable insights into their virulence mechanisms.…”