Influence of L-lactate and low glucose concentrations on the metabolism and the toxin formation of Clostridioides difficile

Departments

Metabolomics & Services

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.

Cite this activity

Hofmann J.D., Biedendieck R., Michel A.-M., Schomburg D., Jahn D. and Neumann-Schaal M.. Influence of L-lactate and low glucose concentrations on the metabolism and the toxin formation of Clostridioides difficile. PLoS One (2021). 10.1371/journal.pone.0244988

Details

Date 01.01.2021
Journal PLoS One
Issue 1
Volume 16
Pages e0244988
Open Access Status Open Access (gold)
Online Ahead Of Print No

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