Epithelial Invasion by Salmonella Typhi using STIV ‐Met Interaction

AbstractTyphoid is a life ‐threatening febrile illness, which affects ~24.2 million people worldwide and is caused by the intracellular bacteria,Salmonella Typhi (S. Typhi). Intestinal epithelial invasion byS. Typhi is essential for the establishment of successful infection and is traditionally believed to depend onSalmonella Pathogenicity Island (SPI1) encoded Type 3 Secretion System (T3SS ‐1). We had previously reported that bacterial outer membrane protein T2942/STIV functions as a standalone invasin and contributes to pathogenesis ofS. Typhi by promoting epithelial invasion independent of T3SS ‐1 (Cell Microbiol, 2015). Here, we show that STIV, using its 20‐amino acid extracellular loop, interacts with receptor tyrosine kinase, Met, of host intestinal epithelial cells. This interaction leads to Met phosphorylation and activation of a downstream signaling cascade, involving Src, PI3‐ K/Akt and Rac1, which culminates into localized actin polymerization and bacterial engulfment by the cell. Inhibition of Met tyrosine kinase activity severely limited intestinal invasion and systemic infection byS. Typhiin vivo, highlighting the importance of this invasion pathway in disease progression. This is the first report elucidating the mechanism of T3SS ‐1‐independent epithelial invasion ofS. Typhi and this crucial host ‐pathogen interaction may be targeted therapeutically to restrict pathogenesis.

Source: Cellular Microbiology - November 13, 2018 Category: Microbiology Authors: Rimi Chowdhury, Sayan Das, Atri Ta, Santasabuj Das Tags: RESEARCH ARTICLE Source Type: research