An AIL family protein promotes type three secretion system-1-independent invasion and pathogenesis of Salmonella enterica serovar Typhi


Rimi Chowdhury, Rahul S. Mandal, Atri Ta, and Santasabuj Das


Adhesion and invasion of Intestinal Epithelial Cells (IECs) are critical for the pathogenesis of Salmonella Typhi, the aetiological agent of human typhoid fever. While type three secretion system-1 (T3SS-1) is a major invasion apparatus of Salmonella, independent invasion mechanisms were described for non-typhoidal Salmonellae. Here, we show that T2942, an AIL-like protein of S. Typhi Ty2 strain, is required for adhesion and invasion of cultured IECs. That invasion was T3SS-1 independent was proved by ectopic expression of T2942 in the non-invasive E. coli BL21 and double-mutant Ty2 (Ty2Δt2942ΔinvG) strains. Laminin and fibronectin were identified as the host-binding partners of T2942 with higher affinity for laminin. Standalone function of T2942 was confirmed by cell adhesion of the recombinant protein, while the protein or anti-T2942 antiserum blocked adhesion/invasion of S. Typhi, indicating specificity. A 20-amino acid extracellular loop was required for invasion, while several loop regions of T2942 contributed to adhesion. Further, T2942 cooperates with laminin-binding T2544 for adhesion and T3SS-1 for invasion. Finally, T2942 was required and synergistically worked with T3SS-1 for pathogenesis of S. Typhi in mice. Considering wide distribution of T2942 among clinical strains, the protein or the 20-mer peptide may be suitable for vaccine development.


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