Summary of project PR001799
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001799. The data can be accessed directly via it's Project DOI: 10.21228/M85M79 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
Project ID: | PR001799 |
Project DOI: | doi: 10.21228/M85M79 |
Project Title: | Exogenous L-Alanine promotes phagocytosis via dual regulations of TLR4 to eliminate multidrug-resistant bacterial pathogens |
Project Type: | MS quantitative analysis |
Project Summary: | 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 multidrug-resistant 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 multidrug-resistant bacteria including V. parahaemolyticus, Escherichia coli, Pseudomonas aeruginosa, 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. |
Institute: | sun yat-sen university |
Last Name: | jiang |
First Name: | ming |
Address: | No. 135, Xingang Xi Road, Guangzhou, 510275, P. R. China, guangzhou, guangdong, 510006, China |
Email: | jiangm28@mail.sysu.edu.cn |
Phone: | 13434283781 |
Summary of all studies in project PR001799
Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
---|---|---|---|---|---|---|---|---|
ST002877 | Metabolic Profiling of Raw264.7 Mouse Macrophage Cells Cultured with Alanine | Mus musculus | Sun Yat-sen University | MS* | 2023-09-26 | 1 | 12 | Uploaded data (83.9M)* |
ST002918 | Metabolic Profiling in mouse Infected with Vibrio parahaemolyticus | Mus musculus | Sun Yat-sen University | MS* | 2023-10-05 | 1 | 92 | Uploaded data (1.7G)* |