Postbiotics from lactic acid bacteria as promising alternatives against urinary tract pathogens

Urinary tract infections (UTIs) are one of the most common bacterial infections in hospital settings and are increasingly difficult to treat due to the rise of antibiotic-resistant uropathogens (UP). Therefore, exploring alternatives to antibiotic therapy is crucial to control the spread of these pathogens. Lactic acid bacteria (LAB) have demonstrated broad antimicrobial activity against various microorganisms, and postbiotics, bioactive compounds derived from these probiotic bacteria, are emerging as a promising tool for controlling such infections. In this study, several LAB strains exhibited antagonistic activity against different clinical UP isolates. To assess whether this activity was due to secreted metabolites, cell-free supernatants (CFSs) were obtained from 24 h LAB cultures. CFSs exhibited variable antimicrobial activity against most UP isolates. Notably, these inhibitory effects were completely lost after pH neutralization and partially reduced by heat or protease treatment, suggesting the involvement of organic acids and/or proteinaceous molecules. CFSs were able to inhibit biofilm formation and partially disrupt mature biofilms of Staphylococcus aureus and Pseudomonas aeruginosa, demonstrating their potential to manage persistent infections. Finally, safety assessment in Caenorhabditis elegans demonstrated that concentrations up to 25% were non-toxic, with no adverse effects on survival, locomotion, or reproduction. Using this infection model, CFS from Lactiplantibacillus paraplantarum CRL 1905 enhanced survival against both pathogens when administered before, during, or after infection, with dose-dependent protective effects. Our findings highlight the potential of LAB-derived postbiotics as safe and effective strategies for preventing and controlling UTIs, particularly in the context of rising antibiotic resistance.