@article{Hofmann2021,
Title = {Influence of L-lactate and low glucose concentrations on the metabolism and the toxin formation of Clostridioides difficile},
Author = {Hofmann, Julia Danielle and Biedendieck, Rebekka and Michel, Annika-Marisa and Schomburg, Dietmar and Jahn, Dieter and Neumann-Schaal, Meina},
Editor = {},
Journal = {PloS one},
Year = {2021},
Pages = {e0244988},
Volume = {16},
Doi = {10.1371/journal.pone.0244988},
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.},
}
TY - JOUR
AU - Hofmann, Julia Danielle
AU - Biedendieck, Rebekka
AU - Michel, Annika-Marisa
AU - Schomburg, Dietmar
AU - Jahn, Dieter
AU - Neumann-Schaal, Meina
TI - Influence of L-lactate and low glucose concentrations on the metabolism and the toxin formation of Clostridioides difficile
T2 - PloS one
PY - 2021
SP - e0244988
VL - 16
DO - 10.1371/journal.pone.0244988
AB - 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.
ER -