The Promising Effect of Ascorbic Acid and Paracetamol as Anti-Biofilm and Anti-Virulence Agents against Resistant Escherichia coli

Escherichia coli is a major cause of serious infections, with antibiotic resistance rendering many treatments ineffective. Hence, novel strategies to combat this pathogen are needed. Anti-virulence therapy is a promising new approach for the subsequent era. Recent research has examined the impact of sub-inhibitory doses of ascorbic acid and paracetamol on Escherichia coli virulence factors. This study evaluated biofilm formation, protease production, motility behavior, serum resistance, expression of virulence-regulating genes (using RT-PCR), and survival rates in a mouse model. Ascorbic acid significantly reduced biofilm formation, protease production, motility, and serum resistance from 100% in untreated isolates to 22–89%, 10–89%, 2–57%, and 31–35% in treated isolates, respectively. Paracetamol also reduced these factors from 100% in untreated isolates to 16–76%, 1–43%, 16–38%, and 31–35%, respectively. Both drugs significantly down-regulated virulence-regulating genes papC, fimH, ompT_m, stcE, fliC, and kpsMTII. Mice treated with these drugs had a 100% survival rate compared with 60% in the positive control group control inoculated with untreated bacteria. This study highlights the potential of ascorbic acid and paracetamol as anti-virulence agents, suggesting their use as adjunct therapies alongside conventional antimicrobials or as alternative treatments for resistant Escherichia coli infections.