Summary of Study ST003053
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
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003053 |
| Study Title | Providing insight into the mechanism of action of Cationic Lipidated Oligomers (CLOs) using metabolomics |
| Study Type | Biomedical research |
| Study 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 | Drug Delivery, Disposition and Dynamics |
| Laboratory | Cornelia Landersdorfer |
| Last Name | Hussein |
| First Name | Maytham |
| Address | Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia |
| maytham.hussein.old@monash.edu | |
| Phone | +61448671141 |
| Submit Date | 2024-01-21 |
| Num Groups | 2 groups x 3 timepoints |
| Total Subjects | NA |
| Num Males | NA |
| Num Females | NA |
| Publications | Providing insight into the mechanism of action of Cationic Lipidated Oligomers (CLOs) using metabolomics |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-01-31 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN005006 | AN005007 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | HILIC | HILIC |
| Chromatography system | Thermo Dionex Ultimate 3000 | Thermo Dionex Ultimate 3000 |
| Column | SeQuant ZIC-HILIC (150 x 4.6mm,3.5um) | SeQuant ZIC-HILIC (150 x 4.6mm,3.5um) |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Q Exactive Orbitrap | Thermo Q Exactive Orbitrap |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | peak height | peak height |
Chromatography:
| Chromatography ID: | CH003782 |
| Chromatography Summary: | pHILIC using basic buffer pH9 |
| Methods Filename: | Metabolomics_pHILIC_Parkville_v1.pdf |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | SeQuant ZIC-HILIC (150 x 4.6mm,3.5um) |
| Column Pressure: | 60 bar at starting conditions. 180 bar at %A |
| Column Temperature: | 25 C |
| Flow Gradient: | 0 min - 80%B, 15 min - 50%B, 18 min - 5%B, 21 min - 5%B, 24 min - 80%B, 32 min - 80%B |
| Flow Rate: | 0.3 ml/min |
| Injection Temperature: | 4 C |
| Internal Standard: | CAPS, CHAPS, PIPES |
| Solvent A: | 100% water; 20 mM ammonium carbonate |
| Solvent B: | 100% acetonitrile |
| Analytical Time: | 32 min |
| Capillary Voltage: | 3.5 kV |
| Oven Temperature: | 25 C |
| Washing Buffer: | syringe wash 50% IPA |
| Weak Wash Solvent Name: | 50% IPA |
| Strong Wash Volume: | 50% IPA |
| Sample Loop Size: | 25 uL |
| Sample Syringe Size: | 25 uL |
| Randomization Order: | yes |
| Chromatography Type: | HILIC |
