Biochemical Analysis of SOD4, a Potential Therapeutic Target for the Emerging Fungal Pathogen .

is an emerging multidrug-resistant fungal pathogen. With high mortality rates, there is an urgent need for new antifungals to combat . Possible antifungal targets include Cu-only superoxide dismutases (SODs), extracellular SODs that are unique to fungi and effectively combat the superoxide burst of host immunity.

Copper-only superoxide dismutase enzymes and iron starvation stress in fungal pathogens.

Copper (Cu)-only superoxide dismutases (SOD) represent a newly characterized class of extracellular SODs important for virulence of several fungal pathogens. Previous studies of the Cu-only enzyme SOD5 from the opportunistic fungal pathogen have revealed that the active-site structure and Cu binding of SOD5 strongly deviate from those of Cu/Zn-SODs in its animal hosts, making Cu-only SODs a possible target for future antifungal drug design. also expresses a Cu-only SOD4 that is highly similar in sequence to SOD5, but is poorly characterized.

Chemical Warfare at the Microorganismal Level: A Closer Look at the Superoxide Dismutase Enzymes of Pathogens.

Superoxide anion radical is generated as a natural byproduct of aerobic metabolism but is also produced as part of the oxidative burst of the innate immune response design to kill pathogens. In living systems, superoxide is largely managed through superoxide dismutases (SODs), families of metalloenzymes that use Fe, Mn, Ni, or Cu cofactors to catalyze the disproportionation of superoxide to oxygen and hydrogen peroxide. Given the bursts of superoxide faced by microbial pathogens, it comes as no surprise that SOD enzymes play important roles in microbial survival and virulence.

Candida albicans FRE8 encodes a member of the NADPH oxidase family that produces a burst of ROS during fungal morphogenesis.

Until recently, NADPH oxidase (NOX) enzymes were thought to be a property of multicellularity, where the reactive oxygen species (ROS) produced by NOX acts in signaling processes or in attacking invading microbes through oxidative damage. We demonstrate here that the unicellular yeast and opportunistic fungal pathogen Candida albicans is capable of a ROS burst using a member of the NOX enzyme family, which we identify as Fre8. C.