Unravelling Salmonella Pathogenesis: Effector-Mediated Post-Translational Modifications, Alternative Therapies, and Advances in Rapid Detection.

Salmonella infections remain a priority concern in both developed and developing regions due to antimicrobial resistance and the lack of proper diagnosis. While substantial progress has been made in deciphering the pathogenesis of this ancient pathogen, emerging insights into host-pathogen interactions, particularly those mediated by post-translational modifications (PTMs) orchestrated by bacterial effectors, offer promising avenues for identifying novel drug targets and advancing host-directed therapies. The rise in antimicrobial resistance among priority Salmonella serovars, particularly in the food industry, underscores the urgent need for effective alternatives to antibiotic therapy alongside rapid and accurate diagnostic tools for identifying drug-resistant strains. In this context, phage therapy, along with probiotics, prebiotics, small molecule inhibitors, optimized antimicrobial peptides, and host-directed therapies, has gained attention as a potential therapeutic approach. Simultaneously, diagnosis tools incorporating modern techniques such as high-throughput gene analysis, multiplex ELISAs, microfluidic devices with nanotechnology, computer modeling, and MALDI-TOF pave the way for improved accuracy, high sensitivity, and affordable solutions to a rising concern of misdiagnosis and dependency on culture-based techniques. This review aims to highlight recent discoveries in post-translational modifications by Salmonella effectors affecting host protein localization and function. We also discuss current progress in alternative therapeutic strategies and next-generation diagnostics aimed at combating drug-resistant Salmonella infections.