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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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Amino acid variation in S. enterica subspecies I FimH.Residues identical to the amino acid sequence of S. Typhimurium SL1344 (Thm1) FimH are indicated by dots. Systemically invasive serovars are shown in red and non-invasive serovars are shown in black. Position -10 represents the position in the signal peptide of unprocessed FimH upstream of the cleavage site.
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ppat-1002733-g002: Amino acid variation in S. enterica subspecies I FimH.Residues identical to the amino acid sequence of S. Typhimurium SL1344 (Thm1) FimH are indicated by dots. Systemically invasive serovars are shown in red and non-invasive serovars are shown in black. Position -10 represents the position in the signal peptide of unprocessed FimH upstream of the cleavage site.

Mentions: The average nucleotide diversity of fimH from S. enterica subspecies I was 1.7±0.2%, with 28 distinct alleles. The majority of the nucleotide polymorphisms were point mutations with a seven-fold higher rate of synonymous over nonsynonymous mutations. The only other polymorphism type was a three-nucleotide insertion (aat) between nucleotide position 864 and 865 in three fimH alleles of Paratyphi B (PaB1, PaB2 and PaB3). There were a total of 27 protein variants encoded by fimH with an overall protein level identity of 96.6% (Figure 2). There were 45 amino acid replacements in the 335 amino acid polypeptide and an asparagine insertion between positions 266 and 267 in Paratyphi B FimH variants. The majority of serovars contained unique FimH variants, but some serovars, e.g., Montevideo and Muenchen; Paratyphi A and Sendai; or Poona, Limete and Pomona, shared the same protein variants of FimH (Figure 2). For some serovars, e.g. Paratyphi B, Choleraesuis and Gallinarum, within-serovar variability of FimH was observed. FimH variations affected the putative leader peptide (22 aa long) as well as a predicted mannose-binding lectin domain (N-terminal 173 aa in the mature protein) and shaft-anchoring pilin domain (C-terminal 136 aa). There was no significant domain clustering or predominance of either conservative or nonconservative protein changes among FimH variants overall or between FimH from systemically invasive and non-invasive serovars (Figure 2).


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)

Amino acid variation in S. enterica subspecies I FimH.Residues identical to the amino acid sequence of S. Typhimurium SL1344 (Thm1) FimH are indicated by dots. Systemically invasive serovars are shown in red and non-invasive serovars are shown in black. Position -10 represents the position in the signal peptide of unprocessed FimH upstream of the cleavage site.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1002733-g002: Amino acid variation in S. enterica subspecies I FimH.Residues identical to the amino acid sequence of S. Typhimurium SL1344 (Thm1) FimH are indicated by dots. Systemically invasive serovars are shown in red and non-invasive serovars are shown in black. Position -10 represents the position in the signal peptide of unprocessed FimH upstream of the cleavage site.
Mentions: The average nucleotide diversity of fimH from S. enterica subspecies I was 1.7±0.2%, with 28 distinct alleles. The majority of the nucleotide polymorphisms were point mutations with a seven-fold higher rate of synonymous over nonsynonymous mutations. The only other polymorphism type was a three-nucleotide insertion (aat) between nucleotide position 864 and 865 in three fimH alleles of Paratyphi B (PaB1, PaB2 and PaB3). There were a total of 27 protein variants encoded by fimH with an overall protein level identity of 96.6% (Figure 2). There were 45 amino acid replacements in the 335 amino acid polypeptide and an asparagine insertion between positions 266 and 267 in Paratyphi B FimH variants. The majority of serovars contained unique FimH variants, but some serovars, e.g., Montevideo and Muenchen; Paratyphi A and Sendai; or Poona, Limete and Pomona, shared the same protein variants of FimH (Figure 2). For some serovars, e.g. Paratyphi B, Choleraesuis and Gallinarum, within-serovar variability of FimH was observed. FimH variations affected the putative leader peptide (22 aa long) as well as a predicted mannose-binding lectin domain (N-terminal 173 aa in the mature protein) and shaft-anchoring pilin domain (C-terminal 136 aa). There was no significant domain clustering or predominance of either conservative or nonconservative protein changes among FimH variants overall or between FimH from systemically invasive and non-invasive serovars (Figure 2).

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