THE ROLE OF THE TYPHOID COLONIZATION FACTOR (TCF) IN THE VIRULENCE OF NON TYPHOIDAL SEROVARS

Salmonella enterica serovars Typhi and Paratyphi A are human-restricted pathogens and the main causative agents of enteric fever. The Typhi colonization factor (Tcf) is a fimbrial apparatus, believed to play a role in the host-specificity of typhoidal serovars to human. Here we show that the tcf operon (comprising the genes tcfABCD, tinR, and tioA) is present in at least 23 non-typhoidal Salmonella (NTS) serovars and demonstrate its expression in clinically important serovars including Schwarzengrund, 9,12:l,v:-, Choleraesuis, Bredeney, Heidelberg, Montevideo, Virchow and Infantis. Although the tcf operon is well conserved among typhoidal and this group of NTS serovars, the N-terminus of the Tcf adhesin, TcfD is highly diverse, suggesting different binding properties of Tcf alleles. Comparison of tcfA expression in typhoidal and NTS serovars demonstrated differences in its expression patterns with the highest expression levels in S. Typhi and S. Infantis. In S. Infantis, Tcf was shown to be induced in rich medium and under microaerobic growth conditions and is negatively regulated by the core leucine-responsive transcriptional regulator (Lrp). Using the colitis mouse model, we demonstrate that while Tcf is dispensable for S. Schwarzengrund and S. Heidelberg colonization, Tcf is required for optimal colonization of S. Infantis in the cecum and the colon. Taken together, our results establish that although the tcf operon is well conserved and expressed in many different NTS serovars, its expression pattern, the TcfD sequence and its role in pathogenicity vary between NTS serovars, indicating that Tcf contributes differently to the virulence of distinct non typhoidal serovars.