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 |
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Collection:
| Collection ID: | CO003161 |
| Collection Summary: | An untargeted metabolomics study was carried out to explore the mechanism(s) of action of C12-o-(BG-D)-10 against MRSA ATCC 43300 using a concentration of 48 µg/mL (i.e. 3×MIC). Samples were taken and analyzed at the 1-, 3-, and 6-h time points in 4 biological replicates. An overnight culture was prepared by inoculating a single colony into 100 mL CAMHB in 250 mL conical flasks (Pyrex) and incubating the suspension in a shaker at 37°C and 180 rpm for ~16 h. After incubation overnight, log-phase cells were prepared in fresh MHB and then incubated for 2 h at 37°C at 180 rpm to log phase with a starting bacterial inoculum of 108 CFU/mL. Then, C12-o-(BG-D)-10 was added to obtain the desired concentration of 48 µg/mL (3 x MIC), in parallel to a CLO-free control for each replicate. The flasks were then incubated at 37°C with shaking at 180 rpm. At each time point (0, 1, 3, and 6 h), 15-mL samples were transferred to 50-mL Falcon tubes for quenching, and the optical density reading at 600 nm (OD600) was then measured and normalized to the pre-treatment level of approximately ~0.5 with fresh CAMHB. Samples were then centrifuged at 3,220 g and 4°C for 10 min, and the supernatants were removed. The pellets were stored at -80°C until metabolite extraction. The experiment was performed in 4 biological replicates to reduce the bias from inherent random variation. |
| Sample Type: | Bacterial cells |
