Salmonellosis as a One Health–One Biofilm Challenge: Biofilm Formation by Salmonella and Alternative Eradication Strategies in the Post-Antibiotic Era

Non-typhoidal <i>Salmonella</i> (NTS) are globally distributed zoonotic pathogens of major concern within the One Health-One Biofilm framework. Fluoroquinolone-resistant <i>Salmonella</i> strains are included by the World Health Organization (WHO) in the Bacterial Priority Pathogens List as high-risk agents. A key virulence determinant of <i>Salmonella</i> is its ability to form biofilms, which may display multidrug-resistant (MDR) characteristics and contribute to bacterial persistence and treatment failure. Animals, particularly poultry and reptiles, represent important reservoirs of <i>Salmonella</i>, and reptile-associated salmonellosis (RAS) may manifest as extraintestinal infections in humans. In the post-antibiotic era, there is an urgent need to identify effective alternatives to conventional therapies. This review summarizes current knowledge on <i>Salmonella</i> biofilms, with particular attention to their MDR potential, and discusses possible strategies for their prevention and eradication, including specific immunoprophylaxis, bacteriophage therapy, and alternative antimicrobials. The promising antimicrobials include plant-based compounds/extracts, bacteriocins, fatty acids, and synthetic/semi-synthetic substances. The integration of vaccination, phage therapy, and novel anti-biofilm compounds may provide a sustainable alternative to antibiotics in controlling <i>Salmonella</i> infections and aligns with the principles of the One Health approach.