ArticlePloS one2021
Influence of L-lactate and low glucose concentrations on the metabolism and the toxin formation of Clostridioides difficile.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 15 citations in OpenAlex.
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- Development of a high-throughput screening platform forAntimicrobial agents and chemotherapy · 2026Article
- Modulation of colonic immunometabolic responses during Clostridioides difficile infection ameliorates disease severity and inflammation.Scientific reports · 2023Article
- Network analysis of toxin production in Clostridioides difficile identifies key metabolic dependencies.PLoS computational biology · 2023Article
- Characterizing metabolic drivers ofFrontiers in pharmacology · 2023Article
- Unveiling the inhibition mechanism ofFrontiers in microbiology · 2023Article
- Thiol Metabolism and Volatile Metabolome ofFrontiers in microbiology · 2022Article
- Predictive regulatory and metabolic network models for systems analysis of Clostridioides difficile.Cell host & microbe · 2021Article
- The metabolic footprint of Clostridia and Erysipelotrichia reveals their role in depleting sugar alcohols in the cecum.Microbiome · 2021Article
- What's a Biofilm?-How the Choice of the Biofilm Model Impacts the Protein Inventory ofFrontiers in microbiology · 2021Article
- Transcriptome Analysis Reveals Catabolite Control Protein A Regulatory Mechanisms Underlying Glucose-Excess or -Limited Conditions in a Ruminal Bacterium,Frontiers in microbiology · 2021Article
- Gut associated metabolites and their roles inGut microbesArticle
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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