Pseudomonas spp. and antimicrobial resistance: unlocking new horizons with 1-hydroxyphenazine.

Antimicrobial resistance (AMR) is a mounting global health challenge projected to cause up to 10 million deaths annually by 2050. Despite advances in antibiotic discovery, the rapid emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens undermines modern medicine, threatening procedures such as surgery, chemotherapy, and organ transplantation. Conventional antibiotics face increasing limitations due to target-site mutations, efflux mechanisms, enzymatic degradation, and biofilm-associated tolerance, underscoring the urgent need for novel antimicrobial strategies. Phenazines, particularly 1-hydroxyphenazine (1-HP), represent promising alternatives owing to their redox activity, broad-spectrum antimicrobial properties, and ecological roles in microbial competition. Recent advances highlight the potential of 1-HP as both a virulence factor and a therapeutic scaffold, with applications spanning agriculture, biotechnology, and medicine. Synthetic biology, metabolic engineering, and nanocarrier-based delivery systems have enabled scalable production and reduced toxicity, while structural modifications such as halogenation have expanded therapeutic potential. This review consolidates historical, mechanistic, and translational insights into 1-HP, emphasizing its dual role as a pathogenic metabolite and a lead compound for future antimicrobial and anticancer development.