Multitarget Antimicrobial Mechanisms of Plant Extracts: A Review of Harnessing Phytochemicals Against Drug-Resistant Pathogens

Abstract

The global rise of antimicrobial resistance threatens the efficacy of current antibiotics and underscores the limitations of the single-target drug paradigm. In response, plant-derived phytochemicals offer a rich, historically validated source of multitarget antimicrobial agents. This review highlights the diverse classes of phytochemicals including alkaloids, flavonoids, terpenoids, and phenolic compounds and their pleiotropic mechanisms of action. These include disrupting microbial membranes, inhibiting key enzymes, interfering with nucleic acid and protein synthesis, and targeting virulence factors like biofilms and quorum sensing. Crucially, many phytochemicals exhibit synergistic interactions both within complex extracts (entourage effect) and when combined with conventional antibiotics, thus enhancing therapeutic potential and mitigating resistance. Despite promising in vitro data, challenges remain in standardization, bioavailability, and regulatory approval. However, integration of ethnobotanical knowledge with modern technologies such as nanotechnology, chemical fingerprinting, and clinical trials offers a viable path forward. Embracing the multitarget nature of phytochemicals is not only innovative but essential in overcoming AMR and revitalizing antimicrobial therapy. This review is based on a structured and systematic search of peer-eviewed literature from major databases including PubMed, Scopus, ScienceDirect, and Google Scholar, covering the period from 2000 to May 2025. Keywords related to phytochemicals and antimicrobial resistance were used, with a focus on original studies, reviews, and credible epidemiological reports from WHO, CDC, and FAO.