Summary of project PR001902
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 PR001902. The data can be accessed directly via it's Project DOI: 10.21228/M8VQ65 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001902 |
| Project DOI: | doi: 10.21228/M8VQ65 |
| Project Title: | Providing insight into the mechanism of action of Cationic Lipidated Oligomers (CLOs) using metabolomics |
| Project Type: | Biomedical research |
| Project Summary: | The increasing resistance of clinically relevant microbes against current commercially available antimicrobials underpins the urgent need for alternative and novel treatment strategies. Cationic lipidated oligomers (CLOs) are innovative alternatives to antimicrobial peptides, and have reported antimicrobial potential. An understanding of their antimicrobial mechanism of action is required to rationally design future treatment strategies for CLOs, either in monotherapy or synergistic combinations. In the present study, metabolomics was used to investigate the potential metabolic pathways involved in the mechanisms of antibacterial activity of one CLO, C12-o-(BG-D)-10, which we have previously shown to be effective against methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. The metabolomes of MRSA ATCC 43300 at 1, 3 and 6 h following treatment with C12-o-(BG-D)-10 (48 µg/mL i.e., 3x MIC) were compared to those of the untreated controls. Our findings reveal that the studied CLO, C12-o-(BG-D)-10, disorganized the bacterial membrane as the first step towards its antimicrobial effect, as evidenced by marked perturbations in the bacterial membrane lipids and peptidoglycan biosynthesis observed at early time points i.e., 1, and 3 h. Central carbon metabolism, and biosynthesis of DNA, RNA, and arginine were also vigorously perturbed, mainly at early time points. Moreover, bacterial cells were under osmotic and oxidative stress across all time points, evident by perturbations of trehalose biosynthesis and pentose phosphate shunt. Overall, this metabolomics study has, for the first time, revealed that the antimicrobial action of C12-o-(BG-D)-10 may potentially stem from the dysregulation of multiple metabolic pathways. |
| Institute: | Monash University |
| Department: | Monash Institute of Pharmaceutical Sciences |
| Laboratory: | Cornelia Landersdorfer |
| Last Name: | Hussein |
| First Name: | Meytham |
| Address: | Monash University, Clayton, Victoria 3800, Australia |
| Email: | maytham.hussein.old@monash.edu |
| Phone: | +61448671141 |
| Publications: | Providing insight into the mechanism of action of Cationic Lipidated Oligomers (CLOs) using metabolomics |
| Contributors: | Maytham Hussein, Muhammad Bilal Hassan Mahboob, James L. Grace, Jessica R. Tait, Véronique Montembault, Laurent Fontaine, John F. Quinn, Tony Velkov, Michael R. Whittaker, Cornelia B. Landersdorfer |
Summary of all studies in project PR001902
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST003053 | Providing insight into the mechanism of action of Cationic Lipidated Oligomers (CLOs) using metabolomics | Staphylococcus aureus | Monash University | MS | 2024-01-31 | 1 | 30 | Uploaded data (2.4G)* |
