Antibacterial and Multi-Target Immunomodulatory Mechanisms of Marine Nocardia rhizosphereae Metabolites: Experimental and Network Pharmacology

The constant increase in multidrug resistance has necessitated bioprospecting of marine actinomycetes for potent antibacterial and immunomodulatory activities. The aim of this study was to investigate the antibacterial and potential host-immunomodulatory mechanisms of secondary metabolites from marine Nocardia rhizosphereae. The extract of N. rhizosphereae was characterised using Gas Chromatography–Mass Spectrometry (GC-MS), and its minimum inhibitory concentration (MIC) was determined by a microdilution assay. Network pharmacology analysis, Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using ShinyGO to elucidate potential host-immunomodulatory mechanisms against bacterial infections. Molecular docking was done using Attracting Cavities on SwissDock. GC–MS spectra revealed 33 compounds, of which 11, including 2-pentanone, 4-amino-4-methyl (50.11%) and 2-hexanol, 2-methyl (25.4%), were reported in extracts with antibacterial activities. The extract exhibited MIC values ranging from 19.55 to 312.5 µg/mL. Key hub targets included ESR1, HSP90AA1 and PPARG. GO enrichment revealed 457 molecular functions, while KEGG analysis illustrated 156 pathways. The best docking poses ranged between –4.99 and −8.69 kcal/mol. In conclusion, the metabolites showed potential antibacterial activity through disruption of bacterial cell-envelope integrity and potential modulation of multiple host-associated molecular targets and signalling pathways.