SOD Enzymes and Microbial Pathogens: Surviving the Oxidative Storm of Infection

Since oxygen appeared in the biosphere some 3–5 billion years ago, all organisms have had to deal with the hazards of potentially damaging reactive oxygen species (ROS), such as superoxide, hydrogen peroxide, and hydroxyl radical. Like all organisms, pathogenic microbes produce ROS as byproducts of aerobic metabolism, but the burden of ROS is magnified when these microbes confront the oxidative burst of the host. As part of the innate immune response, macrophages and neutrophils attack invading microbes with toxic superoxide [1]. To counteract this attack, some microbial pathogens express superoxide dismutase enzymes (SOD). SODs are metalloenzymes that use a redox-active metal to disproportionate two molecules of superoxide to oxygen and hydrogen peroxide, the latter of which is removed by catalase and peroxidase enzymes. SODs have evolved on three separate occasions, yielding a family of Mn and Fe SODs (that use either metal as co-factor), a Cu/Zn SOD family that uses Cu for catalysis, and a rare family of Ni SODs [2]. Why so many SODs? This is best answered in terms of metal bioavailability. In a typical gram-negative bacteria, such as Escherichia coli, the cytosol can have ample Mn and/or Fe, but Cu is extruded into the periplasmic/extracellular space [3]. As a result, Mn and Fe SODs are generally intracellular/cytosolic while Cu/Zn SODs are extracellular/periplasmic (Fig 1). Consistent with the endosymbiosis theory of mitochondrial evolution, this partitioning of SOD enzymes has been retained in eukaryotic mitochondria: The mitochondrial matrix (equivalent to bacterial cytosol) harbors a Mn SOD, while Cu/Zn SOD is in the mitochondrial intermembrane space and cytosol (equivalent to bacterial periplasmic/ extracellular) (Fig 1).