Algal metabolites as emerging anti-virulence therapeutics against Pseudomonas aeruginosa.

Pseudomonas aeruginosa is a multidrug-resistant, opportunistic pathogen that poses a clinical threat due to its ability to form biofilms and regulate virulence through quorum sensing (QS). In addition to shielding bacteria against antimicrobial agents and host defences, biofilms have also been shown to be a cause of persistent and recurrent infections. The World Health Organisation has listed P. aeruginosa as a critical priority pathogen, highlighting the urgent need for novel anti-virulence strategies. As newly discovered alternatives with conventional antibiotic properties, algal metabolites may represent a promising solution; they possess antibiofilm, anti-QS, and anti-virulence properties without the high selective pressure that would prompt the development of resistance. This review emphasizes the role of metabolites produced by micro- and macroalgae in inhibiting QS networks (where bacteria use autoinducers, small signalling molecules to communicate and coordinate biofilm formation or the production of virulence factors based on population density) and biofilm-related gene expression in P. aeruginosa. It is observed that compounds such as phlorotannins, fatty acids, sulphated polysaccharides, and carotenoids impair autoinducer synthesis, competitively block the QS receptors, and inhibit virulence gene expression, including las, rhl, and pqs. These cause a decline in the production of key virulence factors, including pyocyanin, elastase, and rhamnolipids, and weaken the integrity of biofilms. Additionally, recent developments in epigenetic regulation and CRISPR-based gene editing in algae complement the possibility of enhancing metabolite yields and customizing algae profiles for use as potential therapeutics. In contrast to traditional antibacterial agents that target bacterial cell viability, algal metabolites may be able to target internal bacterial communication and virulence pathways, thereby avoiding the induction of resistant phenotypes. This paper summarizes existing evidence, discusses the molecular mechanisms, and highlights the potential of algae-derived compounds as future anti-virulence drugs.