Untargeted LC-HRMS-Based Metabolomic and Antibacterial Potential of Sargassum duplicatum Against Multidrug-Resistant Bacteria

<b><i>Background/Objectives:</i></b> The rise in antimicrobial resistance is one of the major challenges to global health systems, which necessitates the development of new antibacterial compounds. The bioactive compounds of brown seaweed <i>Sargassum duplicatum</i> have demonstrated potential antibacterial activity. This study applied metabolomic profiling and molecular networking in combination with antibacterial screening assays to assess the antimicrobial properties of <i>S. duplicatum</i> extracts against multidrug-resistant bacteria. <b><i>Methods:</i></b> Two extraction methods, i.e., maceration and microwave extraction, were used. Therewith, untargeted metabolomic profiling was performed using Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS). Molecular networks (MNs) were established and compound dereplication was conducted using the spectral database of the Global Natural Products Social Molecular Networking platform (GNPS). Additionally, antimicrobial assays were conducted against Gram-positive and Gram-negative bacterial strains, including multidrug-resistant bacteria, i.e., methicillin-resistant <i>Staphyloccocus aureus</i> ATCC 33592 (MRSA) and β-lactamase, producing <i>Escherichia coli</i> ATCC 35218 (TEM-1 positive strain). <b><i>Result:</i></b> Dereplication resulted in the prediction of six compounds with reported antimicrobial properties, i.e., 13-docosenamide, 9-octadecenamide, pheophorbide A, ouabain, sarmentoside B and AC1L1X1Z. Antibacterial screening of the extracts revealed that the ethyl acetate maceration extracts exhibited the strongest inhibitory activity, with inhibition values between 85 and 98% against <i>S. aureus</i> ATCC 33592. <b><i>Conclusions:</i></b> This metabolomics study requires further research to isolate, purify, confirm, and validate the dereplicated compounds that may have potential antibacterial activity.