Abstract
Uropathogenic Escherichia coli (UPEC) is the leading cause of urinary tract infections (UTIs) and a major contributor to the global antimicrobial resistance crisis. The increasing prevalence of multidrug-resistant (MDR) strains, including expanded-spectrum β-lactamases (ESBL) and carbapenemase-producing isolates, severely limits treatment options. This review provides an overview on the key molecular mechanisms of UPEC antibiotic resistance, such as enzymatic inactivation, target-site mutations, efflux pump activity, and biofilm formation. Beyond conventional antibiotics, special emphasis is placed on phytochemical strategies as promising alternatives. Flavonoids, alkaloids, terpenoids, and essential oils exhibit antibacterial, anti-adhesive, and antibiofilm properties. These natural bioactive compounds modulate motility, suppress fimbrial expression, inhibit quorum sensing, and enhance antibiotic efficacy, acting both as standalone agents and as adjuvants. Current in vitro and in vivo studies highlight the potential of plant-derived compounds and biologically based therapies to combat UPEC. However, challenges related to standardization, bioavailability, and clinical validation remain unresolved. Integrating molecular mechanistic insights with advanced phytochemical research may offers a sustainable and effective strategy for mitigating UPEC antibiotic resistance.