Dataset Information

Methylselenol Produced In Vivo from Methylseleninic Acid or Dimethyl Diselenide Induces Toxic Protein Aggregation in Saccharomyces cerevisiae.

ABSTRACT: Methylselenol (MeSeH) has been suggested to be a critical metabolite for anticancer activity of selenium, although the mechanisms underlying its activity remain to be fully established. The aim of this study was to identify metabolic pathways of MeSeH in Saccharomyces cerevisiae to decipher the mechanism of its toxicity. We first investigated in vitro the formation of MeSeH from methylseleninic acid (MSeA) or dimethyldiselenide. Determination of the equilibrium and rate constants of the reactions between glutathione (GSH) and these MeSeH precursors indicates that in the conditions that prevail in vivo, GSH can reduce the major part of MSeA or dimethyldiselenide into MeSeH. MeSeH can also be enzymatically produced by glutathione reductase or thioredoxin/thioredoxin reductase. Studies on the toxicity of MeSeH precursors (MSeA, dimethyldiselenide or a mixture of MSeA and GSH) in S.cerevisiae revealed that cytotoxicity and selenomethionine content were severely reduced in a met17 mutant devoid of O-acetylhomoserine sulfhydrylase. This suggests conversion of MeSeH into selenomethionine by this enzyme. Protein aggregation was observed in wild-type but not in met17 cells. Altogether, our findings support the view that MeSeH is toxic in S. cerevisiae because it is metabolized into selenomethionine which, in turn, induces toxic protein aggregation.

SUBMITTER: Dauplais M

PROVIDER: S-EPMC7956261 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Methylselenol Produced In Vivo from Methylseleninic Acid or Dimethyl Diselenide Induces Toxic Protein Aggregation in <i>Saccharomyces cerevisiae</i>.

Dauplais Marc M Bierla Katarzyna K Maizeray Coralie C Lestini Roxane R Lobinski Ryszard R Plateau Pierre P Szpunar Joanna J Lazard Myriam M

International journal of molecular sciences 20210224 5

Methylselenol (MeSeH) has been suggested to be a critical metabolite for anticancer activity of selenium, although the mechanisms underlying its activity remain to be fully established. The aim of this study was to identify metabolic pathways of MeSeH in <i>Saccharomyces cerevisiae</i> to decipher the mechanism of its toxicity. We first investigated in vitro the formation of MeSeH from methylseleninic acid (MSeA) or dimethyldiselenide. Determination of the equilibrium and rate constants of the r ...[more]

PMID: 33668124

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Project description:The majority of bacteria detected in the nostril microbiota of most healthy adults belong to three genera: Propionibacterium, Corynebacterium, and Staphylococcus. Among these staphylococci is the medically important bacterium Staphylococcus aureus. Almost nothing is known about interspecies interactions among bacteria in the nostrils. We observed that crude extracts of cell-free conditioned medium from Propionibacterium spp. induce S. aureus aggregation in culture. Bioassay-guided fractionation implicated coproporphyrin III (CIII), the most abundant extracellular porphyrin produced by human-associated Propionibacterium spp., as a cause of S. aureus aggregation. This aggregation response depended on the CIII dose and occurred during early stationary-phase growth, and a low pH (~4 to 6) was necessary but was not sufficient for its induction. Additionally, CIII induced plasma-independent S. aureus biofilm development on an abiotic surface in multiple S. aureus strains. In strain UAMS-1, CIII stimulation of biofilm depended on sarA, a key biofilm regulator. This study is one of the first demonstrations of a small-molecule-mediated interaction among medically relevant members of the nostril microbiota and the first description of a role for CIII in bacterial interspecies interactions. Our results indicate that CIII may be an important mediator of S. aureus aggregation and/or biofilm formation in the nostril or other sites inhabited by Propionibacterium spp. and S. aureus. Importance: Very little is known about interspecies interactions among the bacteria that inhabit the adult nostril, including Staphylococcus aureus, a potential pathogen that colonizes about a quarter of adults. We demonstrated that coproporphyrin III (CIII), a diffusible small molecule excreted by nostril- and skin-associated Propionibacterium spp., induces S. aureus aggregation in a manner dependent on dose, growth phase, and pH. CIII also induces S. aureus to form a plasma-independent surface-attached biofilm. This report is the first description of a role for CIII in bacterial interspecies interactions at any human body site and a novel demonstration that nostril microbiota physiology is influenced by small-molecule-mediated interactions.

Dataset Information

Methylselenol Produced In Vivo from Methylseleninic Acid or Dimethyl Diselenide Induces Toxic Protein Aggregation in Saccharomyces cerevisiae.

Publications

Methylselenol Produced In Vivo from Methylseleninic Acid or Dimethyl Diselenide Induces Toxic Protein Aggregation in <i>Saccharomyces cerevisiae</i>.

Similar Datasets

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