Integrated bioassays and metabolomics identify Cleome noeana as a promising antibacterial candidate

Antimicrobial resistance has intensified the search for novel antibacterial agents from underexplored desert flora. This study compared three arid-region Cleome species to identify the most active candidate against Escherichia coli, Salmonella enterica , and Staphylococcus aureus , and to relate its antibacterial performance to metabolite composition and compatibility with bacteriophage treatment. An in vitro workflow combined crude-extract antibacterial screening, agar diffusion assays, time-kill kinetics, and untargeted GC–MS metabolomics coupled with multivariate analysis. Among the tested species, Cleome noeana exhibited the broadest and strongest antibacterial activity, with minimum inhibitory concentrations of 6.25–25 mg/mL and MBC/MIC ratios ≤ 4. Inhibition zone diameters were inversely correlated with MIC values. Time-kill assays demonstrated that C. noeana extracts reduced viable bacterial counts more rapidly than bacteriophages or antibiotics alone, while extract–phage combinations achieved >99% inhibition within 4 h, indicating phage compatibility with accelerated killing rather than true synergism. Untargeted metabolomic profiling tentatively associated antibacterial activity with phenolic acids, terpenoids, and long-chain fatty acids, including caffeic acid, α-terpineol, and myristic acid. Overall, Cleome noeana emerges as a promising antibacterial species from desert ecosystems and a plant extract compatible with bacteriophage-based approaches, supporting further targeted isolation and in vivo evaluation of its bioactive constituents.