e down regulates several host responses) in comparison to the ub

e. down regulates several host responses) in comparison to the ubiquitous serovars [39]. The lower cytotoxicity and lack of IL-6 responses support this assumption. In contrast to the role in IL-6 induction, none of the mutants differed significantly from the wild type strains in induction of oxidative responses. This result suggested that flagellin was not important for induction of the oxidative response. Results on the role

of flagella and chemotaxis genes in Salmonella host pathogen interaction have been contradictory (compare [12] and [8] with [11]), and we purposely looked for a sensitive assay to show subtle differences between strains. Co-infection assays have been shown to be more sensitive than assays where strains are tested individually [40]. Using Selleckchem LCZ696 this assay, we found that flagella significantly JNK-IN-8 chemical structure influenced the number of bacteria that could be isolated from the spleen 4–5 days post oral infection of mice with S. Dublin, but not with S. Typhimurium. Chemotaxis genes were found to be dispensable in this assay, as previously reported for S. Typhimurium [11]. Animal welfare regulations dictated us to scarify mice when they were severely affected by infection, and this prevented us from using one single end-point of infection. Potentially, this may have influenced the competitive indexes for S. Typhimurium, since this serovar propagated at different speed at systemic sites depending

on the presence of flagella genes (see below). However, all mice were killed within a 24 hours period, and we do not believe that this significantly influenced our results. Like cheA mutation, mutation of cheR confers a constitutively smooth swimming phenotype. We have not included this gene in our investigation, and we cannot rule out that it may have a different role in host pathogen interaction than cheA. We have performed preliminary testing of an S. Dublin cheR mutant and found that it corresponds to cheA with respect to phenotypes in cell assays and oral challenge of mice (unpublished), however, we do not have S. Typhimurium results to compare it

to. Flagella have been found to be important for the outcome of oral infection with S. Typhimurium in streptomycin treated mice, which is a model for studies of the entero-pahtogenesis of Salmonella[41]. In this model flagella Protein tyrosine phosphatase are essential for initiation of inflammation, creating an environment in which Salmonella prevails over the normal flora, and in this model, chemotaxis genes were also essential for the outcome of infection. Cattle are the natural host for S. Dublin, and in addition to differences caused by the choice of animal model, studies have shown that virulence factors may differ depending on the host [42]. This must be taken into account when concluding on the current results. The changes in virulence observed when flagella were removed were relatively modest.

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