Natural product-based inhibitors of quorum sensing: A novel approach to combat antibiotic resistance

Abstract

The global rise of antibiotic resistance (AR) presents a critical threat to public health, prompting the search for innovative antimicrobial strategies. Quorum sensing (QS), a bacterial communication system that governs virulence, biofilm formation, and resistance, has emerged as a compelling non-lethal therapeutic target. This review explores the potential of natural product-based quorum sensing inhibitors (QSIs) derived from plants, microbes, and marine organisms. These compounds disrupt QS pathways through various mechanisms, including inhibition of signal synthesis, receptor antagonism, enzymatic degradation of signaling molecules, and suppression of QS-regulated gene expression. Particular emphasis is placed on the molecular targets and synergistic potential of natural QSIs when combined with conventional antibiotics to enhance efficacy and curb resistance development. This narrative review explores the diverse sources of natural QSIs, including plant-derived phytochemicals, microbial secondary metabolites, and marine bioactive compounds. In this study, a thorough literature search was conducted using databases such as PubMed, Scopus, Web of Science, and Google Scholar. Studies selected were those published between 2013 and 2025 in peer-reviewed journals. The manuscript also examines translational challenges such as poor bioavailability, bacterial adaptability, and regulatory barriers, alongside innovative strategies including nanoparticle-based delivery and combination therapies. Finally, clinical and industrial applications of QSIs are discussed, reinforcing their promise as sustainable tools for combating resistant infections and biofilm-associated diseases. This review underscores QS inhibition as a transformative approach in the ongoing battle against antibiotic resistance. Graphical abstract (Created in https://BioRender.com ). • Natural QS inhibitors reduce virulence without inducing resistance pressure. • Plant, marine, and microbial compounds disrupt quorum sensing pathways. • QS inhibitors enhance antibiotic efficacy and biofilm penetration. • Synergistic therapies show promise against multidrug-resistant bacteria. • Nanodelivery and combination therapy improve QSI clinical potential.