Pseudomonas aeruginosa : Pathogenesis‐Immunity Arm Race, Vaccine and Therapeutics Development Panoramas

ABSTRACT Pseudomonas aeruginosa is a multidrug‐resistant opportunistic pathogen that causes severe infections in immunocompromised individuals, particularly those with cystic fibrosis, chronic obstructive pulmonary disease (COPD), cancer, immunodeficiency, burn injuries, and severe infections requiring ventilation, such as Long‐COVID. Despite its wide use as a model bacterium, its clinical prevalence and importance, and the development of multiple vaccines and therapeutics in research and trials over the past five decades, no vaccines or therapeutics have been approved, and none are in active clinical development. Moreover, our knowledge of the contributions, race, and interplay of their adaptable arsenal of virulence factors or pathogenic mechanisms with host immunity remains a relatively black box. We have only begun to see new research investigating alternative vaccines and therapeutic approaches in recent years. Here, we briefly review the current scope of mechanisms of host immunity evasion, virulence regulation via quorum sensing (QS), and biofilm formation in Pseudomonas aeruginosa infection. Recent advancements in vaccine development, including conjugate vaccines, live‐attenuated strains, and mRNA‐based platforms, are discussed alongside emerging therapies such as antibody‐based therapies, antimicrobial peptides, nanoparticle‐based antimicrobials, phage‐derived endolysins, natural bioactive compounds, and bacteriophage‐based interventions. Challenges in clinical translation and future directions for combating this resilient pathogen are highlighted.