Revealing quorum-sensing networks in Pseudomonas aeruginosa infections through internal and external signals to prevent new resistance trends

In the context of growing antibiotic resistance in bacteria, the quorum-sensing (QS) system of Pseudomonas aeruginosa (P. aeruginosa) has become a target for new therapeutic strategies. QS is a crucial communication process and an essential pathogenic mechanism. This comprehensive review explores the critical role of QS in the pathogenesis of P. aeruginosa infections, including lung, burn, bloodstream, gastrointestinal, corneal, and urinary tract infections. In addition, this review delves into the complexity of the bacterial QS communication network and highlights the intricate mechanisms underlying these pathological processes. Notably, in addition to the four main QS systems, bacterial QS can interact with various external and internal signaling networks, such as host environments and nutrients in the external microbiome, as well as internal virulence regulation systems within bacteria. These elements can significantly influence the behavior and virulence of microbial communities. Therefore, this review reveals that inhibitors targeting singular QS pathways may inadvertently promote virulence in other pathways, leading to new trends in drug resistance. In response to evolving resistance challenges, this study proposes more cautious treatment strategies, including multitarget interventions and combination therapies, aimed at combating the escalating issue of resistance.