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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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Related in: MedlinePlus

DNA-based protein phylogram of S. enterica FimH, derived from ZP analysis.The tree was built based on the 50 fimH sequences of S. enterica subsp. I. Each circle represents a unique structural variant, and the size of the circle is proportional to the number of representative sequences. The dashed line separates the long-term (green) from the recently emerged variants (black). Branches marked in blue indicate branches containing synonymous mutations. The length of each branch is proportional to the number of non-synonymous mutations that were acquired. The strain tags of systemically invasive serovars are in red and the non-invasive serovars in black.
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ppat-1002733-g003: DNA-based protein phylogram of S. enterica FimH, derived from ZP analysis.The tree was built based on the 50 fimH sequences of S. enterica subsp. I. Each circle represents a unique structural variant, and the size of the circle is proportional to the number of representative sequences. The dashed line separates the long-term (green) from the recently emerged variants (black). Branches marked in blue indicate branches containing synonymous mutations. The length of each branch is proportional to the number of non-synonymous mutations that were acquired. The strain tags of systemically invasive serovars are in red and the non-invasive serovars in black.

Mentions: When the FimH protein variants were analyzed for emergence from an evolutionary perspective, most FimH variants (20 out of 27) appeared to have emerged relatively recently, without accumulation of silent changes in the coding alleles (Figure 3). The rest of the FimH variants were of a relatively long-term evolutionary origin, with accumulation of silent changes in the corresponding alleles or along the surrounding branches on the tree. Interestingly, while the systemically non-invasive serovars included nine recent and six long-term FimH variants, only one of twelve FimH variants from systemically invasive serovars was of long-term origin (pā€Š=ā€Š0.04). Moreover, alleles of the majority (10 of 12) of FimH variants from systemically invasive serovars evolved from the nearest allele exclusively by structural mutations.


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)

DNA-based protein phylogram of S. enterica FimH, derived from ZP analysis.The tree was built based on the 50 fimH sequences of S. enterica subsp. I. Each circle represents a unique structural variant, and the size of the circle is proportional to the number of representative sequences. The dashed line separates the long-term (green) from the recently emerged variants (black). Branches marked in blue indicate branches containing synonymous mutations. The length of each branch is proportional to the number of non-synonymous mutations that were acquired. The strain tags of systemically invasive serovars are in red and the non-invasive serovars in black.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1002733-g003: DNA-based protein phylogram of S. enterica FimH, derived from ZP analysis.The tree was built based on the 50 fimH sequences of S. enterica subsp. I. Each circle represents a unique structural variant, and the size of the circle is proportional to the number of representative sequences. The dashed line separates the long-term (green) from the recently emerged variants (black). Branches marked in blue indicate branches containing synonymous mutations. The length of each branch is proportional to the number of non-synonymous mutations that were acquired. The strain tags of systemically invasive serovars are in red and the non-invasive serovars in black.
Mentions: When the FimH protein variants were analyzed for emergence from an evolutionary perspective, most FimH variants (20 out of 27) appeared to have emerged relatively recently, without accumulation of silent changes in the coding alleles (Figure 3). The rest of the FimH variants were of a relatively long-term evolutionary origin, with accumulation of silent changes in the corresponding alleles or along the surrounding branches on the tree. Interestingly, while the systemically non-invasive serovars included nine recent and six long-term FimH variants, only one of twelve FimH variants from systemically invasive serovars was of long-term origin (pā€Š=ā€Š0.04). Moreover, alleles of the majority (10 of 12) of FimH variants from systemically invasive serovars evolved from the nearest allele exclusively by structural mutations.

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