Biological treatments for zoonotic salmonellosis: an evolving therapeutic landscape

Salmonellosis, a predominant food-borne gastroenteric disease, presents a substantial and escalating threat to global public health, largely attributable to infections by non-typhoidal <i>Salmonella</i> serovars such as <i>Salmonella enterica</i> serovar <i>Typhimurium</i> (<i>S. Typhimurium</i>) and <i>Salmonella</i> serovar <i>Enteritidis</i> (<i>S. Enteritidis</i>). The conventional reliance on antimicrobial agents for treating salmonellosis is increasingly compromised by the emergence and spread of multidrug-resistant (MDR) strains, necessitating an urgent shift toward alternative therapeutic strategies. In recent years, biological therapies, including bacteriophages, probiotics, vaccines and their synergistic combinations, have demonstrated considerable promise. Advances in antibacterial research highlight the potential of biotherapies to offer high efficacy with minimal side effects. This review consolidates the most current information on the methodologies, mechanisms of action, functional benefits, and clinical research progress of these biological treatments in combating zoonotic salmonellosis. We delve into recent innovations such as engineered phages and probiotics, postbiotics, novel vaccine platforms including mRNA and nanoparticle-based delivery systems, and the development of multivalent vaccines. Furthermore, the importance of the One Health perspective in controlling salmonellosis and the translational challenges, including regulatory and commercialization hurdles, are discussed. It is anticipated that biotherapies, particularly engineered and combination approaches, hold significant potential for addressing the challenge of MDR bacteria and safeguarding public and animal health.