Evaluation of the Antibacterial Potency of Phytochemicals and Their Effects on Host Xenobiotic Response Using Caenorhabditis elegans

Antimicrobial resistance poses a huge challenge to the healthcare system, prompting the need to develop new remedies to fight bacterial infection. Natural products derived from herbs and spices are gaining interest as potential antibacterial agents as they are generally regarded as safe for consumption. This study investigates the correlation between antibacterial efficacy and host response of six phytochemicals: berberine, curcumin, capsaicin, 6-gingerol, piperine, and allicin. The inhibitory and sensitization effects of the tested phytochemicals against Bacillus subtilis, methicillin-resistant Staphylococcus aureus, Escherichia coli, Salmonella Typhimurium, and Pseudomonas aeruginosa were evaluated. Curcumin and berberine exhibited potent inhibitory activity against Gram-positive bacteria. They enhanced the susceptibility of MRSA to ampicillin and tetracycline by 4-fold. Curcumin and berberine also increased the susceptibility of B. subtilis to tetracycline by 4-fold and 2-fold, respectively. Despite weaker bacterial inhibition, capsaicin treatment reduced the MIC for tetracycline by 4-fold in B. subtilis. Allicin, piperine, and 6-gingerol showed weak antibacterial and no sensitization effect. Analysis of the in vivo xenobiotic responses in Caenorhabditis elegans revealed that berberine and piperine strongly induced the detoxification mechanism genes (cyp-35C1, gst-5, ugt-21, ugt-25, irg-4), indicating elevated stress in the host. Curcumin and capsaicin moderately upregulated detoxification enzyme genes and repressed the stress response genes (irg-4, hsp-16.2), indicating a lower adverse host response. Allicin and 6-gingerol exhibited mild xenobiotic response. The bacterial sensitization effects of curcumin and capsaicin, coupled with their mild xenobiotic response, suggest their potential application as antibacterial agents.