TolC contributes to antimicrobial resistance, exopolysaccharide production, and virulence.

is a Gram-negative bacterium that causes a variety of human diseases, ranging from pneumonia to urinary tract infections and invasive diseases. The emergence of strains that are resistant to multiple antibiotics has made treatment more complex and led to becoming a global health threat. Addressing this threat necessitates the development of new therapeutic strategies to combat this pathogen, including strategies to overcome antimicrobial resistance and therapeutics for novel targets such as antivirulence. Here, we investigated the function of TolC, an outer membrane protein essential for the function of tripartite transporters, in . Mutation of rendered hypersensitive to multiple antibiotics. Moreover, the mutation impaired capsule production and affected the expression of key capsule biosynthetic genes, indicating a regulatory role for TolC in capsule biosynthesis. Additionally, TolC was essential for growth under iron-limiting conditions, suggesting its involvement in iron acquisition. The mutant exhibited increased adherence to human enterocytes and enhanced serum sensitivity. In the infection model, the mutant displayed reduced virulence compared to the wild type. Our findings highlight the pleiotropic role of TolC in pathobiology, influencing antimicrobial resistance, capsule production, iron homeostasis, adherence to host cells, and virulence. Understanding the multifaceted role of TolC in may guide the development of new therapeutic strategies against this pathogen. .