GC-MS

The rise of multidrug-resistant pathogens and the emergence of new microbes due to climate change highlight the urgent need for alternative antimicrobials. Plants, as they adapt to environmental shifts, produce diverse metabolites with potent antibacterial properties, offering a sustainable source to combat antibiotic resistance and emerging microbial threats. In this context, Citrullus colocynthis fruits, known for their antimicrobial activity and adaptation to the hot Gulf region, were screened to identify accessions with strong antibacterial activity and distinct metabolic profiles. Rinds and pulps of three accessions were tested for their effectiveness against Staphylococcus aureus and Escherichia coli, with findings showing that most activity came from the fruit rind, not the pulp. Minimum inhibitory concentration (MIC50) tests confirmed the superior antibacterial activity of rind extracts against S. aureus, particularly accession S2, which had an MIC50 of 15.74 µg/ml, outperforming other accessions. Metabolic profiling via GC-MS/MS revealed distinct clusters for rind versus pulp, with unique metabolites such as butyric acid, α-linolenic acid, and β-sitosterol, known for their antimicrobial properties. Enrichment analysis indicated that unsaturated fatty acid biosynthesis and other fatty acid metabolism pathways were enriched in the accession S2 rind, supporting its antibacterial potency. Network analysis pinpointed bacterial fatty acid synthase enzymes (FabZ, FabI, and FabH) as potential S. aureus targets of C. colocynthis rind fatty acids. This selection of accessions with unique adaptability and antimicrobial profiles offers a promising strategy for developing plant-based nutraceuticals to combat multidrug-resistant pathogen.