Anthranilate Reduces Pseudomonas aeruginosa Infection Severity through an Antibiotic-Independent Anti-Virulence Mechanism

Background/Objectives: Antibiotic resistance is a growing global health challenge, especially with tricky bacteria like Pseudomonas aeruginosa. Anthranilate, previously identified as a signaling molecule in P. aeruginosa, modulates various pathogenicity-related phenotypes by reducing virulence factor production, inhibiting biofilm formation, and increasing antibiotic susceptibility. Based on these good properties as an anti-virulence agent, this study evaluated the actual therapeutic potential of anthranilate using mouse skin infection and lung infection models. Specifically, the efficacy of anthranilate in a standalone treatment was investigated without reliance on conventional antibiotics. Methods: The therapeutic efficacy of anthranilate was evaluated in murine skin and lung infection models of P. aeruginosa. Anthranilate was administered as a standalone treatment, and its effects on bacterial burden, inflammatory responses, and tissue lesion progression were assessed and compared with those of gentamicin treatment. Results: Anthranilate effectively reduced bacterial suppuration, mitigated inflammatory responses, and suppressed lesion progression in infected skin and lung tissues. Notably, anthranilate alone produced therapeutic effects comparable to those of gentamicin. Conclusions: These findings highlight its potential of standalone treatment as an alternative to traditional antibiotics and offer a novel anti-virulence strategy that minimizes selective pressure for resistance development.