Strategies for quorum sensing inhibition as a tool for controlling Pseudomonas aeruginosa infections
Bárbara Rodríguez-Urretavizcaya, Lluı̈sa Vilaplana, M.‐Pilar Marco
Abstract
• Promising alternative antimicrobial therapeutic strategies focus on blocking bacterial processes unrelated to viability. • Inhibiting bacterial communication by targeting the quorum sensing (QS) system blocks virulence pathways activation and biofilm formation. • Strategies to disrupt the P. aeruginosa QS system include disrupting QS signalling molecule (autoinducers, AIs) biosynthetic pathways. • Few QS inhibitors have reached the clinical stage because their drug-likeness must be improved. Antibiotic resistance is one of the most important concerns in global health today. A growing number of infections are becoming harder to treat with conventional drugs and fewer new antibiotics are being developed. In this context, strategies based on blocking or attenuating virulence pathways that do not focus on eradication of bacteria are potential therapeutic approaches that should reduce the selective pressure exerted on the pathogen. This virulence depletion can be achieved by inhibiting the conserved quorum sensing (QS) system, a mechanism that enables bacteria to communicate with one another in a density-dependent manner. QS regulates gene expression, leading to the activation of important processes such as virulence and biofilm formation. This review highlights the approaches reported so far for disrupting different steps of the QS system of the multiresistant pathogen Pseudomonas aeruginosa. The authors describe different types of molecules (including enzymes, natural and synthetic small molecules, and antibodies) already identified as P. aeruginosa quorum quenchers (QQs) or QS inhibitors (QSIs), grouped according to the QS circuit that they block (Las, Rhl, Pqs and some examples from the controversial pathway Iqs). The discovery of new QQs and QSIs is expected to help reduce antibiotic doses, or at least to provide options that act as adjuvants to enhance the effect of antibiotic treatment. Moreover, this article outlines the advantages and possible drawbacks of each strategy and provides perspectives on the potential developments in this field in the future.