title: An AIL family protein promotes type three secretion system-1-independent invasion and pathogenesis of Salmonella enterica serovar Typhi.
abstract: 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.
authors.affiliation: Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases, P-33 Scheme XM C.I.T. Road, Beliaghata Kolkata, 700010, India.
authors.forename: Rimi
authors.initials: R
authors.lastname: Chowdhury
authors.forename: Rahul S
authors.initials: RS
authors.lastname: Mandal
authors.forename: Atri
authors.initials: A
authors.lastname: Ta
authors.forename: Santasabuj
authors.initials: S
authors.lastname: Das
mesh_terms: D001422:Bacterial Adhesion; D001426:Bacterial Proteins / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004705:Endocytosis; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism; D015870:Gene Expression; D019073:HT29 Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D007797:Laminin / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012485:Salmonella typhi / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D005353:Fibronectins; D007797:Laminin; D050505:Mutant Proteins; D011994:Recombinant Proteins