Dual anti-pseudomonal and resistance-modulatory actions of <i>Sida acuta</i> (Malvaceae) via BamB–OprM targeting: insights from integrated metabolomics, computational, and <i>in vitro</i> analyses

Abstract

CONTEXT: presents a pressing global health challenge and demands novel solutions. Medicinal plants offer a largely untapped reservoir of structurally diverse compounds with promising antibacterial and adjuvant potential. OBJECTIVE: Burm.f. (Malvaceae) as a reservoir of dual-target phytochemicals capable of modulating resistance. MATERIALS AND METHODS: An integrated workflow combining LC/Q-TOF-MS metabolomic profiling, molecular docking (MD), dynamics simulations (MDS), and microbiological assays was applied to the ethyl acetate fraction of the aerial parts (SAAP-EA). RESULTS: (MIC 32-256 µg/mL) and synergized with β-lactams, fluoroquinolones, and tetracyclines, achieving up to 64-fold MIC reductions at sub-inhibitory doses. The dual inhibition of membrane assembly and efflux likely underlies the observed resistance-breaking effects, facilitating intracellular antibiotic accumulation. DISCUSSION AND CONCLUSIONS: validation and preclinical optimization of lead dual-target adjuvants.