Quorum Quenchers as an Emerging New Strategy against Pseudomonas aeruginosa Infections

Abstract

Antimicrobial resistance (AMR) poses a critical global health threat, leading to approximately 1.27 million deaths annually from infectious diseases resistant to existing antibiotics. Factors such as antibiotic misuse and environmental contamination have accelerated AMR, with the COVID-19 pandemic exacerbating the issue due to increased antibiotic usage. However, the development of new antibiotics has stagnated, with only a few approved in recent years, and many facing resistance. Among the priority pathogens identified by the WHO, Pseudomonas aeruginosa stands out as a significant concern due to its multidrug resistance and virulence. P. aeruginosa infections are challenging to treat due to intrinsic and acquired resistance mechanisms, as well as its ability to form biofilms. Additionally, P. aeruginosa produces a plethora of virulence factors, including proteases, siderophores, and toxins, further complicating treatment. Quorum sensing (QS) systems play a crucial role in regulating bacterial physiology and virulence factor expression. P. aeruginosa employs three QS systems, making it an attractive target for quorum quenching (QQ) strategies. Enzymes such as AHL lactonases, acylases, and oxidoreductases have shown promise in inhibiting QS, thus reducing virulence without impacting bacterial growth. Furthermore, natural QS inhibitors produced by various organisms offer potential therapeutic alternatives. Despite promising results in vitro, translating QQ strategies to clinical settings remains challenging. Nevertheless, QQ represents a novel approach in combating multidrug-resistant infections and warrants further investigation as a complementary therapeutic strategy alongside traditional antibiotics. This review summarizes enzymes with Qurorum Quenching activity evaluated against the pathogen P. aeruginosa and their potential applications in combination therapies.