Exogenous L-Alanine promotes phagocytosis multidrug-resistant bacterial pathogens (V. parahaemolyticus-infected spleen metabolomics)

ABSTRACT:

Multidrug-resistant bacteria present a major threat to public health. Therefore, new drugs or approaches are urgently needed to manage and mitigate this threat. Here, we screen the molecular candidates that allow the survival of mice upon Vibrio parahaemolyticus infection by integrated proteomic and metabolomics analysis, where L-Alanine metabolism and phagocytosis are highly correlated. The role of L-Alanine on boosting mouse survival is further confirmed with in vivo bacterial challenge studies on bacteria including V. parahaemolyticus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae. Functional studies demonstrate that exogenous L-Alanine promotes phagocytosis to these different species of multidrug-resistant pathogens. The underlying mechanism involves two events that are L-Alanine-dependently increased TLR4 expression and L-Alanine-enhanced TLR4 signaling via increasing the biosynthesis and secretion of fatty acids such as palmitate. Palmitate enhances the binding of LPS to TLR4 and thereby promotes TLR4 dimmer formation and endocytosis for the subsequent activation of PI3K/Akt and NF-κB pathways and phagocytosis of bacteria. These results suggest that modulation of metabolic environment is a plausible approach for combating infection with multidrug-resistant bacteria.

V. parahaemolyticus-infected spleen metabolomics is reported in the current study MTBLS7996.

L-Alanine-treated macrophage metabolomics is reported in MTBLS7986.

INSTRUMENT(S): Gas Chromatography MS -

PROVIDER: MTBLS7996 | MetaboLights | 2024-09-26

REPOSITORIES: MetaboLights