Candida albicans Expresses an Unusual Cytoplasmic Manganese-containing Superoxide Dismutase (SOD3 Gene Product) upon the Entry and during the Stationary Phase

Abstract

We report here that in addition to a cytoplasmic copper-zinc-containing superoxide dismutase (SOD) and a mitochondrial manganese-containing SOD, Candida albicans expresses a third SOD gene (SOD3). The deduced amino acid sequence contains all of the motifs found in previously characterized manganese-containing SODs, except the presence of a mitochondrial transit peptide. Recombinant Sod3p expressed and purified from Escherichia coli is a homotetramer with a subunit mass of 25.4 kDa. Mass absorption spectrometry detected the presence of both iron and manganese in purified Sod3p but, as determined by metal replacement experiments, the enzyme displays activity only when bound to manganese. Overexpression of SOD3 was shown to rescue the hypersensitivity to redox cycling agents of a Saccharomyces cerevisiae mutant lacking the cytoplasmic copper-zinc-containing SOD. Northern blot analyses showed that the transcription of SOD3 is induced neither by the transition from the yeast to the mycelial form of C. albicans nor by drug-induced oxidative stress. In continuous cultures, the expression of SOD3 was strongly stimulated upon the entry and during the stationary phase, concomitantly with the repression of SOD1. We conclude that Sod3p is an atypical cytosolic manganese-containing superoxide dismutase that is involved in the protection of C. albicans against reactive oxygen species during the stationary phase.

Superoxide dismutases and glutaredoxins have a distinct role in the response of Candida albicans to oxidative stress generated by the chemical compounds menadione and diamide

“…The ability to combat ROS is vital for microbial pathogenesis to either cope with ROS generated as a consequence of their own metabolism or escape from human phagocytic cells (Cabiscol et al 2000, Lamarre et al 2001, Hwang et al 2002, Martchenko et al 2004, Gonzalez-Parraga et al 2005. Some chemical compounds have been used to induce oxidative stress in microorganisms, such as menadione and diamide.…”

“…SOD5 has been demonstrated to relate to hyphae formation by transcript profiling; i.e., this gene is up-regulated during the process of hyphae formation (Nantel et al 2002) Furthermore, Martchenko et al (2004 demonstrated with Northern analysis that SOD5 expression during hyphae formation is due to the presence of serum. SOD1 is also transcribed in the presence of serum (Lamarre et al 2001), which could explain why a double mutant for two oxidative stress genes (GRX2 and SOD1) is defective in hyphae formation.…”

“…In addition to combating reactive oxygen species (ROS) from their own metabolism, pathogenic organisms also react against the primary oxidative burst generated by macrophages and polymorphonuclear neutrophils (PMNs), which utilise the nicotinamide adenine dinucleotide phosphate oxidase present in the membrane to produce the superoxide anion (O 2 -) (Battistoni et al 1998, Lamarre et al 2001 .…”

Manganese activation of superoxide dismutase 2 in Saccharomyces cerevisiae requires MTM1 , a member of the mitochondrial carrier family

“…However, C. albicans expresses a cytosolic form of Mn-SOD that is reported to be active when expressed in the cytosol of S. cerevisiae. This Mn-SOD, named SOD3, shares 60% sequence identity with S. cerevisiae mitochondrial SOD2 and clearly requires manganese for activity (31). In fact, C. albicans SOD3 cross-reacts well with an antibody directed against S. cerevisiae SOD2 (Fig.…”

Candida albicans adapts to host copper during infection by swapping metal cofactors for superoxide dismutase

“…Curiously, the C. albicans genome contains an unusually large number of genes that encode SODs. Although most eukaryotes express only two or three SODs, C. albicans has six (26,(31)(32)(33). C. albicans Sod4, Sod5, and Sod6 are extracellular members of the Cu/Zn SOD family (33)(34)(35)(36).…”