evolution of salmonella enterica virulence via point mutations in the fimbrial adhesin whereas the majority of pathogenic salmonella serovars are capable of infecting many different animal species typically producing a selflimited gastroenteritis serovars with narrow hostspecificity exhibit increased virulence and their infections frequently result in fatal systemic diseases in our study a genetic and functional analysis of the mannosespecific type 1 fimbrial adhesin fimh from a variety of serovars of salmonella enterica revealed that specific mutant variants of fimh are common in hostadapted systemically invasive serovars we have found that while the lowbinding sheardependent phenotype of the adhesin is preserved in broad hostrange usually systemically noninvasive salmonella the majority of hostadapted serovars express fimh variants with one of two alternative phenotypes a significantly increased binding to mannose as in s typhi s paratyphi c s dublin and some isolates of s choleraesuis or complete loss of the mannosebinding activity as in s paratyphi b s choleraesuis and s gallinarum the functional diversification of fimh in hostadapted salmonella results from recently acquired structural mutations many of the mutations are of a convergent nature indicative of strong positive selection the highbinding phenotype of fimh that leads to increased bacterial adhesiveness to and invasiveness of epithelial cells and macrophages usually precedes acquisition of the nonbinding phenotype collectively these observations suggest that activation or inactivation of mannosespecific adhesive properties in different systemically invasive serovars of salmonella reflects their dynamic trajectories of adaptation to a life style in specific hosts in conclusion our study demonstrates that point mutations are the target of positive selection and in addition to horizontal gene transfer and genome degradation events can contribute to the differential pathoadaptive evolution of salmonella