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Evolution of Salmonella enterica virulence via point mutations in the fimbrial adhesin.

Kisiela DI, Chattopadhyay S, Libby SJ, Karlinsey JE, Fang FC, Tchesnokova V, Kramer JJ, Beskhlebnaya V, Samadpour M, Grzymajlo K, Ugorski M, Lankau EW, Mackie RI, Clegg S, Sokurenko EV - PLoS Pathog. (2012)

Bottom Line: 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.The functional diversification of FimH in host-adapted Salmonella results from recently acquired structural mutations.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.

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.

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Schematic representation of evolutionary changes in the FimH binding phenotype of selected S. enterica serovars.The evolutionary changes in the FimH of S. Enteritidis, S. Pullorum, S. Gallinarum and S. Dublin (A), S. Indiana, S. Paratyphi C and S. Choleraesuis (B), S. Paratyphi B (C) and S. Paratyphi A, S. Sendai and S. Typhi (D). Low (green)-FimH with low-binding phenotype; High (blue)-FimH with high-binding phenotype; None (orange)-inactive variant of FimH. The strain tags of systemically non-invasive serovars are in black and the systemically invasive serovars in red. Structural mutations are given along each arrow. Structural hot-spot mutations are underlined. The activating mutations are in blue and the inactivating mutations are in orange. The FimH variants from strains with phylogenetic relatedness supported by MLST are shown in tan boxes.
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ppat-1002733-g005: Schematic representation of evolutionary changes in the FimH binding phenotype of selected S. enterica serovars.The evolutionary changes in the FimH of S. Enteritidis, S. Pullorum, S. Gallinarum and S. Dublin (A), S. Indiana, S. Paratyphi C and S. Choleraesuis (B), S. Paratyphi B (C) and S. Paratyphi A, S. Sendai and S. Typhi (D). Low (green)-FimH with low-binding phenotype; High (blue)-FimH with high-binding phenotype; None (orange)-inactive variant of FimH. The strain tags of systemically non-invasive serovars are in black and the systemically invasive serovars in red. Structural mutations are given along each arrow. Structural hot-spot mutations are underlined. The activating mutations are in blue and the inactivating mutations are in orange. The FimH variants from strains with phylogenetic relatedness supported by MLST are shown in tan boxes.

Mentions: We compared amino acid sequences of high-binding and inactive FimH variants with their closest FimH ancestors exhibiting low-binding phenotypes (Figure 1). According to the fimH phylogeny, the low-binding phenotype is evolutionarily ancestral to the high-binding FimH and, in most cases, non-binding variants evolved from high-binding variants (Figure 5). For example, high-binding variants of FimH of S. Paratyphi C and S. Choleraesuis (Chl5–Chl6) evolved from the low-binding variant of S. Indiana; and the non-binding FimH of S. Choleraesuis (Chl1–Chl4) evolved from the high-binding FimH of S. Choleraesuis (Chl5–Chl6). In the case of S. Paratyphi B, the whole spectrum of phenotypes evolved within the serovar. The non-binding phenotype of S. Gallinarum biovar Pullorum appeared to evolve from low-binding variants of S. Enteriditis, with the former then giving rise to two non-binding FimH variants of S. Gallinarum biovar Gallinarum. Interestingly, with the exception of S. Typhi FimH, all microevolutionary changes in the gene observed in systemically invasive serovars occurred exclusively via amino acid replacements, i.e., without accumulation of any silent mutations, suggesting the action of strong positive selection. In addition, some of the mutations occurred repeatedly (P35L, T56I) or in the same amino acid position (V41G and V41C) indicating convergent evolution of the FimH variants, also a strong indicator of positive selection. Importantly, the evolutionary changes of the fimH variants correspond to serovar phylogeny based on MLST data (Figure 5, light orange boxes).


Evolution of Salmonella enterica virulence via point mutations in the fimbrial adhesin.

Kisiela DI, Chattopadhyay S, Libby SJ, Karlinsey JE, Fang FC, Tchesnokova V, Kramer JJ, Beskhlebnaya V, Samadpour M, Grzymajlo K, Ugorski M, Lankau EW, Mackie RI, Clegg S, Sokurenko EV - PLoS Pathog. (2012)

Schematic representation of evolutionary changes in the FimH binding phenotype of selected S. enterica serovars.The evolutionary changes in the FimH of S. Enteritidis, S. Pullorum, S. Gallinarum and S. Dublin (A), S. Indiana, S. Paratyphi C and S. Choleraesuis (B), S. Paratyphi B (C) and S. Paratyphi A, S. Sendai and S. Typhi (D). Low (green)-FimH with low-binding phenotype; High (blue)-FimH with high-binding phenotype; None (orange)-inactive variant of FimH. The strain tags of systemically non-invasive serovars are in black and the systemically invasive serovars in red. Structural mutations are given along each arrow. Structural hot-spot mutations are underlined. The activating mutations are in blue and the inactivating mutations are in orange. The FimH variants from strains with phylogenetic relatedness supported by MLST are shown in tan boxes.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369946&req=5

ppat-1002733-g005: Schematic representation of evolutionary changes in the FimH binding phenotype of selected S. enterica serovars.The evolutionary changes in the FimH of S. Enteritidis, S. Pullorum, S. Gallinarum and S. Dublin (A), S. Indiana, S. Paratyphi C and S. Choleraesuis (B), S. Paratyphi B (C) and S. Paratyphi A, S. Sendai and S. Typhi (D). Low (green)-FimH with low-binding phenotype; High (blue)-FimH with high-binding phenotype; None (orange)-inactive variant of FimH. The strain tags of systemically non-invasive serovars are in black and the systemically invasive serovars in red. Structural mutations are given along each arrow. Structural hot-spot mutations are underlined. The activating mutations are in blue and the inactivating mutations are in orange. The FimH variants from strains with phylogenetic relatedness supported by MLST are shown in tan boxes.
Mentions: We compared amino acid sequences of high-binding and inactive FimH variants with their closest FimH ancestors exhibiting low-binding phenotypes (Figure 1). According to the fimH phylogeny, the low-binding phenotype is evolutionarily ancestral to the high-binding FimH and, in most cases, non-binding variants evolved from high-binding variants (Figure 5). For example, high-binding variants of FimH of S. Paratyphi C and S. Choleraesuis (Chl5–Chl6) evolved from the low-binding variant of S. Indiana; and the non-binding FimH of S. Choleraesuis (Chl1–Chl4) evolved from the high-binding FimH of S. Choleraesuis (Chl5–Chl6). In the case of S. Paratyphi B, the whole spectrum of phenotypes evolved within the serovar. The non-binding phenotype of S. Gallinarum biovar Pullorum appeared to evolve from low-binding variants of S. Enteriditis, with the former then giving rise to two non-binding FimH variants of S. Gallinarum biovar Gallinarum. Interestingly, with the exception of S. Typhi FimH, all microevolutionary changes in the gene observed in systemically invasive serovars occurred exclusively via amino acid replacements, i.e., without accumulation of any silent mutations, suggesting the action of strong positive selection. In addition, some of the mutations occurred repeatedly (P35L, T56I) or in the same amino acid position (V41G and V41C) indicating convergent evolution of the FimH variants, also a strong indicator of positive selection. Importantly, the evolutionary changes of the fimH variants correspond to serovar phylogeny based on MLST data (Figure 5, light orange boxes).

Bottom Line: 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.The functional diversification of FimH in host-adapted Salmonella results from recently acquired structural mutations.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, University of Washington, Seattle, Washington, United States of America.

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.

Show MeSH
Related in: MedlinePlus