The superoxide dismutases of Candida glabrata protect against oxidative damage and are required for lysine biosynthesis, DNA integrity and chronological life survival

Briones-Martin-del-Campo, Marcela; Orta-Zavalza, Emmanuel; Cañas-Villamar, Israel; Gutiérrez-Escobedo, Guadalupe; Juárez-Cepeda, Jacqueline; Robledo-Márquez, Karina; Arroyo-Helguera, Omar; Castaño, Irene; Peñas, Alejandro De Las

doi:10.1099/mic.0.000006

Cited by 24 publications

(18 citation statements)

References 67 publications

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“…Although S. cerevisiae is benign, it is closely related to C. glabrata (32,36). Finally, C. glabrata is also known to have robust antioxidative defenses that allow it to survive in the phagosome (57,58) and that may impact its ability to resist oxidative killing by cationic phenylene ethynylenes.…”

Section: Discussionmentioning

confidence: 99%

Antifungal Properties of Cationic Phenylene Ethynylenes and Their Impact on β-Glucan Exposure

Pappas

Sylejmani

Graus

et al. 2016

Antimicrob Agents Chemother

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Candida species are the cause of many bloodstream infections through contamination of indwelling medical devices. These infections account for a 40% mortality rate, posing a significant risk to immunocompromised patients. Traditional treatments against Candida infections include amphotericin B and various azole treatments. Unfortunately, these treatments are associated with high toxicity, and resistant strains have become more prevalent. As a new frontier, light-activated phenylene ethynylenes have shown promising biocidal activity against Gram-positive and -negative bacterial pathogens, as well as the environmental yeast Saccharomyces cerevisiae. In this study, we monitored the viability of Candida species after treatment with a cationic conjugated polymer [poly(p-phenylene ethynylene); PPE] or oligomer ["end-only" oligo(p-phenylene ethynylene); EO-OPE] by flow cytometry in order to explore the antifungal properties of these compounds. The oligomer was found to disrupt Candida albicans yeast membrane integrity independent of light activation, while PPE is able to do so only in the presence of light, allowing for some control as to the manner in which cytotoxic effects are induced. The contrast in killing efficacy between the two compounds is likely related to their size difference and their intrinsic abilities to penetrate the fungal cell wall. Unlike EO-OPE-DABCO (where DABCO is quaternized diazabicyclo[2,2,2]octane), PPE-DABCO displayed a strong propensity to associate with soluble ␤-glucan, which is expected to inhibit its ability to access and perturb the inner cell membrane of Candida yeast. Furthermore, treatment with PPE-DABCO unmasked Candida albicans ␤-glucan and increased phagocytosis by Dectin-1-expressing HEK-293 cells. In summary, cationic phenylene ethynylenes show promising biocidal activity against pathogenic Candida yeast cells while also exhibiting immunostimulatory effects.

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Section: Discussionmentioning

confidence: 99%

Antifungal Properties of Cationic Phenylene Ethynylenes and Their Impact on β-Glucan Exposure

Pappas

Sylejmani

Graus

et al. 2016

Antimicrob Agents Chemother

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“…For example, Saccharomyces cerevisiae and Candida glabrata lacking SOD1 (a cytosolic Cu/Zn‐SOD) both show obvious growth defects and increased sensitivity to redox‐cycling drugs, such as menadione (Manfredini et al ., ; Briones‐Martin‐del‐Campo et al . ). In Candida albicans , a SOD1 knockout (a cytosolic Cu/Zn‐SOD) exhibits attenuated virulence in an animal model of systemic infection (Hwang et al ., ; Chaves et al ., ) and is more susceptible to killing by macrophages (Hwang et al ., ) and polymorphonuclear neutrophils (PMNs) (Chaves et al ., ).…”

Section: Introductionmentioning

confidence: 97%

An extracellular Zn‐only superoxide dismutase from Puccinia striiformis confers enhanced resistance to host‐derived oxidative stress

Liu

Guan

Zheng

et al. 2016

Environmental Microbiology

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Accumulation of reactive oxygen species (ROS) following plant-pathogen interactions can trigger plant defence responses and directly damage pathogens. Thus, it is essential for pathogens to scavenge host-derived ROS to establish a parasitic relationship. However, the mechanisms protecting pathogens from host-derived oxidative stress remain unclear. In this study, a superoxide dismutase (SOD) gene, PsSOD1, was cloned from a wheat-Puccinia striiformis f. sp. tritici (Pst) interaction cDNA library. Transcripts of PsSOD1 were up-regulated in the early infection stage. Heterologous mutant complementation and biochemical characterization revealed that PsSOD1 encoded a Zn-only SOD. The predicted signal peptide was functional in an invertase-mutated yeast strain. Furthermore, immunoblot analysis of apoplastic proteins in Pst-infected wheat leaves and bimolecular fluorescence complementation suggested that PsSOD1 is a secreted protein that potentially forms a dimer during Pst infection. Overexpression of PsSOD1 enhanced Schizosaccharomyces pombe resistance to exogenous superoxide. Transient expression of PsSOD1 in Nicotiana benthamiana suppressed Bax-induced cell death. Knockdown of PsSOD1 using a host-induced gene silencing (HIGS) system reduced the virulence of Pst, which was associated with ROS accumulation in HIGS plants. These results suggest that PsSOD1 is an important pathogenicity factor that is secreted into the host-pathogen interface to contribute to Pst infection by scavenging host-derived ROS.

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“…MnSOD deficiency in S. pombe causes both osmotic and heat sensitivity, suggesting that in this organism MnSod2p plays a general role in protection against multiple stresses [ 61 ]. We may thus speculate that MpSod2p may have a general role in protection against heat sensitivity as well ( Figure 4 and Figure 5 ; [ 22 , 28 ]), since functional over-expression of Z-SOD2 genes (in multi-copy plasmid) of Z. rouxii improved salt resistance of some S. cerevisiae WT under acidic conditions [ 73 ].…”

Section: Resultsmentioning

confidence: 99%

“…In the case of Candida glabrata the absence of both SODs leads to auxotrophy for lysine, a high rate of spontaneous mutation and reduced chronological lifespan. In a more general context SODs also play an important role in metabolism, acting in biosynthesis, DNA protection and aging [ 28 ]. In the yeast S. cerevisiae , SOD enzymes play a substantial role in preserving the genomic integrity and their absence leads to shorter life span by allowing increased DNA fragmentation [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Altered Phenotypes in Saccharomyces cerevisiae by Heterologous Expression of Basidiomycete Moniliophthora perniciosa SOD2 Gene

Melo

Santos

Melgaço

et al. 2015

IJMS

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Heterologous expression of a putative manganese superoxide dismutase gene (SOD2) of the basidiomycete Moniliophthora perniciosa complemented the phenotypes of a Saccharomyces cerevisiae sod2Δ mutant. Sequence analysis of the cloned M. perniciosa cDNA revealed an open reading frame (ORF) coding for a 176 amino acid polypeptide with the typical metal-binding motifs of a SOD2 gene, named MpSOD2. Phylogenetic comparison with known manganese superoxide dismutases (MnSODs) located the protein of M. perniciosa (MpSod2p) in a clade with the basidiomycete fungi Coprinopsis cinerea and Laccaria bicolor. Haploid wild-type yeast transformants containing a single copy of MpSOD2 showed increased resistance phenotypes against oxidative stress-inducing hydrogen peroxide and paraquat, but had unaltered phenotype against ultraviolet–C (UVC) radiation. The same transformants exhibited high sensitivity against treatment with the pro-mutagen diethylnitrosamine (DEN) that requires oxidation to become an active mutagen/carcinogen. Absence of MpSOD2 in the yeast sod2Δ mutant led to DEN hyper-resistance while introduction of a single copy of this gene restored the yeast wild-type phenotype. The haploid yeast wild-type transformant containing two SOD2 gene copies, one from M. perniciosa and one from its own, exhibited DEN super-sensitivity. This transformant also showed enhanced growth at 37 °C on the non-fermentable carbon source lactate, indicating functional expression of MpSod2p. The pro-mutagen dihydroethidium (DHE)-based fluorescence assay monitored basal level of yeast cell oxidative stress. Compared to the wild type, the yeast sod2Δ mutant had a much higher level of intrinsic oxidative stress, which was reduced to wild type (WT) level by introduction of one copy of the MpSOD2 gene. Taken together our data indicates functional expression of MpSod2 protein in the yeast S. cerevisiae.

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The superoxide dismutases of Candida glabrata protect against oxidative damage and are required for lysine biosynthesis, DNA integrity and chronological life survival

Cited by 24 publications

References 67 publications

Antifungal Properties of Cationic Phenylene Ethynylenes and Their Impact on β-Glucan Exposure

Antifungal Properties of Cationic Phenylene Ethynylenes and Their Impact on β-Glucan Exposure

An extracellular Zn‐only superoxide dismutase from Puccinia striiformis confers enhanced resistance to host‐derived oxidative stress

Altered Phenotypes in Saccharomyces cerevisiae by Heterologous Expression of Basidiomycete Moniliophthora perniciosa SOD2 Gene

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