Influence of L-lactate and low glucose concentrations on the metabolism and the toxin formation of Clostridioides difficile
| Autor: | Hofmann, Julia Danielle, Biedendieck, Rebekka, Michel, Annika-Marisa, Schomburg, Dietmar, Jahn, Dieter, Neumann-Schaal, Meina |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pyruvate
Metabolic Processes Clostridium Difficile Science Toxic Agents Bacterial Toxins Carbohydrates Toxicology Pathology and Laboratory Medicine Biochemistry Glucose Metabolism Bacterial Proteins Medicine and Health Sciences Genetics Toxins Metabolomics Lactic Acid Metabolites Glucose metabolism Glucose Transcriptome analysis Gene expression Bacteria Organic Compounds Clostridioides difficile Monosaccharides Organic Chemistry Gut Bacteria Chemical Compounds Organisms Biology and Life Sciences Computational Biology Genomics Ketones Genome Analysis Chemistry Metabolism Sweetening Agents Physical Sciences Fermentation Metabolome Carbohydrate Metabolism Medicine Transcriptome Analysis Acids Research Article |
| Zdroj: | PLOS ONE, 16(1):e0244988 PLoS ONE, Vol 16, Iss 1, p e0244988 (2021) PLoS ONE |
| DOI: | 10.1371/journal.pone.0244988#sec019 |
| Popis: | The virulence of Clostridioides difficile (formerly Clostridium difficile) is mainly caused by its two toxins A and B. Their formation is significantly regulated by metabolic processes. Here we investigated the influence of various sugars (glucose, fructose, mannose, trehalose), sugar derivatives (mannitol and xylitol) and L-lactate on toxin synthesis. Fructose, mannose, trehalose, mannitol and xylitol in the growth medium resulted in an up to 2.2-fold increase of secreted toxin. Low glucose concentration of 2 g/L increased the toxin concentration 1.4-fold compared to growth without glucose, while high glucose concentrations in the growth medium (5 and 10 g/L) led to up to 6.6-fold decrease in toxin formation. Transcriptomic and metabolic investigation of the low glucose effect pointed towards an inactive CcpA and Rex regulatory system. L-lactate (500 mg/L) significantly reduced extracellular toxin formation. Transcriptome analyses of the later process revealed the induction of the lactose utilization operon encoding lactate racemase (larA), electron confurcating lactate dehydrogenase (CDIF630erm_01321) and the corresponding electron transfer flavoprotein (etfAB). Metabolome analyses revealed L-lactate consumption and the formation of pyruvate. The involved electron confurcation process might be responsible for the also observed reduction of the NAD+/NADH ratio which in turn is apparently linked to reduced toxin release from the cell. |
| Databáze: | OpenAIRE |
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