Abstract

Urinary tract infections (UTIs) are among the most prevalent bacterial infections worldwide, with uropathogenic Escherichia coli (UPEC) serving as the primary causative agent. Although antibiotic therapy remains the standard of care for UTI treatment, the increasing prevalence of antimicrobial resistance has substantially reduced the effectiveness of commonly prescribed antibiotics. Resistance to trimethoprim-sulfamethoxazole (TMP-SMX), β-lactams, and fluoroquinolones is particularly concerning, as these agents constitute the principal therapeutic options for UTIs. This review examines the molecular mechanisms underlying UPEC resistance to these three classes of antibiotics, including target site modifications, efflux pump overexpression, porin regulation, and enzymatic degradation. Furthermore, it explores how these resistance determinants contribute to the development of multidrug-resistant (MDR) UPEC strains, which demonstrate cross-resistance to multiple antibiotics and present significant challenges for clinical management. Novel therapeutic strategies, such as efflux pump inhibitors, bacteriophage therapy, and genomic-guided precision medicine, are under investigation as potential solutions to address the growing global burden of MDR UPEC, alongside alternative non-antibiotic treatments. This review aims to provide a comprehensive overview of the genetic and regulatory pathways driving antibiotic resistance in UPEC, offering insights that may guide the development of effective treatment strategies and help mitigate the ongoing spread of antimicrobial resistance.

• Keywords: Uropathogenic Escherichia coli, Antibiotic resistance, Multidrug resistance, Urinary tract infections, Efflux pumps