Biotherapeutic strategies for quorum quenching in Salmonella Typhi: a review

Quorum sensing (QS) in Salmonella enterica serovar Typhi (S. Typhi) is a cell-cell communication process mediated by molecules like Autoinducer-2 (AI-2). The production and detection of these molecules are population density-dependent, regulating behaviours essential to virulence and survival. Since the QS stage lies between the initial planktonic stage and the formation of a stable, persistent biofilm, it allows the pathogen to survive and become more virulent. Eradication of S. Typhi requires investigation using effective therapeutic agents, such as biologically-derived therapeutics. Conventional antibiotics have significant limitations when used against S. Typhi. Their efficacy is often hampered by different resistance problems, and they can cause various clinical complications related to their chemical and physical properties. The prolonged use of these drugs can cause host toxicity and may fail to eradicate the pathogen. The persistence of biofilms and the emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pan-drug-resistant (PDR) strains have rendered many existing drugs ineffective. Thus, targeting bacterial communication by simply disrupting its signalling mechanism, i.e., QS, might be a better approach for therapeutic development against biofilms. This review aims to critically evaluate current QS inhibitors (QSIs) and, more importantly, to explore the potential of developing bioorganic compounds from natural and biological sources as effective quorum quenching (QQ) agents.