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.

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Study IDST003053
Study TitleProviding insight into the mechanism of action of Cationic Lipidated Oligomers (CLOs) using metabolomics
Study TypeBiomedical research
Study SummaryThe 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
DepartmentDrug Delivery, Disposition and Dynamics
LaboratoryCornelia Landersdorfer
Last NameHussein
First NameMaytham
AddressMonash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Victoria 3800, Australia
Emailmaytham.hussein.old@monash.edu
Phone+61448671141
Submit Date2024-01-21
Num Groups2 groups x 3 timepoints
Total SubjectsNA
Num MalesNA
Num FemalesNA
PublicationsProviding insight into the mechanism of action of Cationic Lipidated Oligomers (CLOs) using metabolomics
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2024-01-31
Release Version1
Maytham Hussein Maytham Hussein
https://dx.doi.org/10.21228/M8VQ65
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Bacteria; Subject species: Staphylococcus aureus (Factor headings shown in green)

mb_sample_id local_sample_id treatment
SA331534T_1h_1C12-o-(BG-D)-10_1h
SA331535T_1h_4C12-o-(BG-D)-10_1h
SA331536T_1h_3C12-o-(BG-D)-10_1h
SA331537T_1h_2C12-o-(BG-D)-10_1h
SA331538T_3h_3C12-o-(BG-D)-10_3h
SA331539T_3h_2C12-o-(BG-D)-10_3h
SA331540T_3h_1C12-o-(BG-D)-10_3h
SA331541T_3h_4C12-o-(BG-D)-10_3h
SA331542T_6h_2C12-o-(BG-D)-10_6h
SA331543T_6h_3C12-o-(BG-D)-10_6h
SA331544T_6h_1C12-o-(BG-D)-10_6h
SA331545T_6h_4C12-o-(BG-D)-10_6h
SA331546Control_1h_4Control_1h
SA331547Control_1h_2Control_1h
SA331548Control_1h_3Control_1h
SA331549Control_1h_1Control_1h
SA331550Control_3h_4Control_3h
SA331551Control_3h_1Control_3h
SA331552Control_3h_2Control_3h
SA331553Control_3h_3Control_3h
SA331554Control_6h_3Control_6h
SA331555Control_6h_1Control_6h
SA331556Control_6h_2Control_6h
SA331557Control_6h_4Control_6h
SA331558Blank_2Extraction blank
SA331559Blank_3Extraction blank
SA331560Blank_1Extraction blank
SA331561QC_1Pooled QC
SA331562QC_2Pooled QC
SA331563QC_3Pooled QC
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