Abstract
Whereas the majority of pathogenic Salmonella serovars are capable of infecting many different animal species, typically producing a self-limited gastroenteritis, serovars with narrow host-specificity exhibit increased virulence and their infections frequently result in fatal systemic diseases. In our study, a genetic and functional analysis of the mannose-specific type 1 fimbrial adhesin FimH from a variety of serovars of Salmonella enterica revealed that specific mutant variants of FimH are common in host-adapted (systemically invasive) serovars. We have found that while the low-binding shear-dependent phenotype of the adhesin is preserved in broad host-range (usually systemically non-invasive) Salmonella, the majority of host-adapted 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 mannose-binding activity (as in S. Paratyphi B, S. Choleraesuis and S. Gallinarum). The functional diversification of FimH in host-adapted Salmonella results from recently acquired structural mutations. Many of the mutations are of a convergent nature indicative of strong positive selection. The high-binding phenotype of FimH that leads to increased bacterial adhesiveness to and invasiveness of epithelial cells and macrophages usually precedes acquisition of the non-binding phenotype. Collectively these observations suggest that activation or inactivation of mannose-specific 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.
Highlights
Salmonella enterica is comprised of six subspecies (I, II, IIIa, IIIb, IV and VI) further subdivided into,2,500 serovars based on the presence of distinct surface antigens
By analysis of the mannose-sensitive fimbrial adhesin FimH, we demonstrate that in addition to horizontal gene transfer and genome degradation, single amino acid replacement plays an important role in the differential adaptive evolution of Salmonella
We show that acquisition of specific structural mutations in FimH variants of host-adapted serovars results in either significantly enhanced or, alternatively, completely inactivated mannose-binding, whereas systemically non-invasive serovars retain a primordial relatively low-binding phenotype
Summary
Salmonella enterica is comprised of six subspecies (I, II, IIIa, IIIb, IV and VI) further subdivided into ,2,500 serovars based on the presence of distinct surface antigens (somatic O, flagellar H and capsular Vi). The vast majority of Salmonella strains pathogenic to humans belong to subspecies I Enterica), which is considered to be adapted to warm-blooded animals unlike the remaining subspecies which are found mostly in reptiles [1,2]. Heterogeneity in Salmonella virulence has been traditionally attributed to different distributions of various mobile genetic elements such as chromosomal pathogenicity islands, bacteriophages, transposons, plasmids, etc. The distribution of these factors does not correlate well with differences in clinical features. Gene loss via deletion, insertional inactivation or truncation has been considered important in the evolution of highly pathogenic Salmonella [6,7,8]. We demonstrate that amino acid mutations in core genes of Salmonella are a driving force behind pathoadaptive evolution of Salmonella serovars
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