Summary of project PR002304
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 PR002304. The data can be accessed directly via it's Project DOI: 10.21228/M8T82V This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002304 |
| Project DOI: | doi: 10.21228/M8T82V |
| Project Title: | (p)ppGpp and DksA play crucial role in reducing the efficacy of ꞵ-lactam antibiotics by modulating bacterial membrane permeability |
| Project Type: | Metabolomics |
| Project Summary: | The key signaling molecules in the bacterial stress sensing pathway, the alarmone (p)ppGpp and transcription factor DksA, help in survival during nutritional deprivation and exposure to xenobiotics by modulating cellular metabolic pathways. In Vibrio cholerae, (p)ppGpp metabolism is solely linked with the functions of three proteins: RelA, SpoT, and RelV. At threshold or elevated concentrations of (p)ppGpp, the level of cellular metabolites and proteins in the presence and absence of DksA in V. cholerae and other bacteria has not yet been comprehensively studied. We engineered the genome of V. cholerae to develop DksA null mutants in the presence and absence of (p)ppGpp biosynthetic enzymes. We observed a higher sensitivity of the (p)ppGpp0ΔdksA V. cholerae mutant to different ꞵ-lactam antibiotics compared to the wild-type (WT) strain. Our whole-cell metabolomic and proteome analysis revealed that the cell membrane and peptidoglycan biosynthesis pathways are significantly altered in the (p)ppGpp0, ΔdksA, and (p)ppGpp0ΔdksA V. cholerae strains. Further, the mutant strains displayed enhanced inner and outer membrane permeability in comparison to the WT strains. These results directly correlate with the tolerance and survival of V. cholerae to ꞵ-lactam antibiotics. These findings may help in the development of adjuvants for ꞵ-lactam antibiotics by inhibiting the functions of stringent response modulators. |
| Institute: | Translational Health Science And Technology Institute (THSTI) |
| Department: | Biology |
| Laboratory: | Biomarker lab |
| Last Name: | Kumar |
| First Name: | Yashwant |
| Address: | NCR Biotech Science Cluster, Faridabad, Haryana, 121001, India |
| Email: | y.kumar@thsti.res.in |
| Phone: | 01292876496 |
| Funding Source: | THSTI |
Summary of all studies in project PR002304
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003711 | (p)ppGpp and DksA play crucial role in reducing the efficacy of ꞵ-lactam antibiotics by modulating bacterial membrane permeability | Vibrio cholerae | Translational Health Science And Technology Institute (THSTI) | MS* | 2025-03-04 | 1 | 72 | Uploaded data (1.4G)* |
