Salmonella enterica serovar Typhi is a human-restricted pathogen and the causative agent of enteric (typhoid) fever disease. The typhoid colonization factor (Tcf) is a fimbrial apparatus, which is secreted via the chaperone-usher pathway and has been proposed to play a role in S. Typhi host-specificity to humans. In typhoidal serovars (S. Typhi and S. Paratyphi A), the tcf operon is encoded within the Salmonella pathogenicity island (SPI)-6 and includes four genes: tcfABCD followed by two additional ORFs, tinR and tioA with unknown functions. Here we show that although Tcf is considered a typhoid-specific virulence factor, the tcf operon is actually present in clinical isolates of non-typhoidal Salmonella (NTS) from serovars Schwarzengrund, 9,12:l,v:-, Choleraesuis, Heidelberg, Montevideo, Virchow, Bredeney and Infantis. This entire region, have been horizontally acquired and integrated between the core Salmonella genes sinR and pagN. Regulation analysis showed differences in the expression patterns of tcf between typhoidal and NTS serovars, including upregulation of the tcf in NTS at the mid-logarithmic phase. To characterize the role of the tcf operon in the virulence of NTS serovars in-vivo, an in-frame deletion of the tcf operon in S. Schwarzengrund, S. Infantis and S. Heidelberg was constructed. We demonstrated that cecum and colon colonization of S. Infantis strain lacking the Tcf is significantly impaired in the mouse model. Collectively, our results establish that the tcf operon is present in different NTS serovars and is playing a key role in the colonization of S. Infantis in the colitis mouse model.
