Phytochemical interventions in bacterial resistance: plant metabolites as next-generation antibacterial agents

Abstract

The increasing prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacterial pathogens poses a critical challenge to global health. In response, plant-derived natural products have emerged as promising candidates for the development of novel antibacterial agents. This review comprehensively evaluates 235 plant-based compounds, including alkaloids, terpenoids, phenolics, lignans, saponins, and glycosides, known for their antibacterial activity. The literature was systematically searched through several academic databases, including PubMed, Scopus, and Web of Science, using relevant keywords such as “plant-derived antibacterial agents,” “phytochemicals,” “MDR bacteria,” “XDR bacteria,” and specific compound classes like “alkaloids,” “terpenoids,” and “phenolics.” The 262 articles were selected based on their relevance to antibacterial activity, resistance mechanisms, and pharmacological data. A combination of inclusion and exclusion criteria was applied, with a focus on peer-reviewed studies published between 2015 and 2025. The primary objective of this study is to explore the antibacterial potential of these phytochemicals against Gram-positive and Gram-negative bacteria, with a particular emphasis on resistant clinical strains. Each compound group is examined for its mechanism of action, minimum inhibitory concentration (MIC), and any reported synergistic effects with conventional antibiotics. Many of the reviewed compounds demonstrated potent antibacterial activity, often with MIC values below 10 μg/mL, and exhibited mechanisms such as membrane disruption, enzyme inhibition, and efflux pump interference. These findings underscore the relevance of plant secondary metabolites in addressing antibiotic resistance and provide a framework for their further development as therapeutic agents. The study encourages the continued exploration of plant biodiversity for sustainable antibacterial drug discovery.