Limits...
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.

Show MeSH

Related in: MedlinePlus

Maximum-likelihood DNA phylograms of S. enterica fimH and concatenated MLST loci (aroC, hisD and thrA).The fimH tree (A) was built based on an alignment of fimH sequences amplified from 55 isolates including 45 different strains of subspecies I and 10 strains of subspecies II–VI (for details see Table 1). Five additional alleles of fimH obtained from GenBank (S. Typhimurium AJB3 (Thm3), S. Typhimurium LB5010 (Thm4), S. Gallinarum 287/91 (Gal1) and 589/02 (Gal2), and S. Paratyphi C 49 [RKS4594] (PaC1) were included. The MLST loci tree (B) was built on an alignment of concatenated sequences of three genes (aroC, hisD and thrA) obtained for 57 study strains. The trees shown were rooted using S. enterica subsp. II (2993). The italicized values along the branches denote % bootstrap values based on 1000 runs (the bootstrap proportions along the terminal branches separating isolates within single serovars as well as the ones below 50% are not shown). Systemically invasive serovars are shown in red and non-invasive serovars are shown in black. Strain tags are as used in the text.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3369946&req=5

ppat-1002733-g001: Maximum-likelihood DNA phylograms of S. enterica fimH and concatenated MLST loci (aroC, hisD and thrA).The fimH tree (A) was built based on an alignment of fimH sequences amplified from 55 isolates including 45 different strains of subspecies I and 10 strains of subspecies II–VI (for details see Table 1). Five additional alleles of fimH obtained from GenBank (S. Typhimurium AJB3 (Thm3), S. Typhimurium LB5010 (Thm4), S. Gallinarum 287/91 (Gal1) and 589/02 (Gal2), and S. Paratyphi C 49 [RKS4594] (PaC1) were included. The MLST loci tree (B) was built on an alignment of concatenated sequences of three genes (aroC, hisD and thrA) obtained for 57 study strains. The trees shown were rooted using S. enterica subsp. II (2993). The italicized values along the branches denote % bootstrap values based on 1000 runs (the bootstrap proportions along the terminal branches separating isolates within single serovars as well as the ones below 50% are not shown). Systemically invasive serovars are shown in red and non-invasive serovars are shown in black. Strain tags are as used in the text.

Mentions: fimH was amplified from 55 of 56 S. enterica isolates, of which 45 represented 22 serovars of subspecies I, and 11 isolates represented other subspecies (Table 1). The isolate of S. enterica subsp. IIIa (2980) carried only part of the fimH gene and was excluded from further analysis. The maximum-likelihood phylogenetic tree constructed based on 55 amplified fimH sequences and five additional fimH alleles obtained from GenBank (fimH of S. Typhimurium AJB3 and LB5010, S. Gallinarum 287/91 and 589/02, and S. Paratyphi C 49 [RKS 4594]) is presented in Figure 1A. The fimH sequences of subspecies I (enterica) were grouped in a distinct phylogenetic clade separate from fimH of subspecies II–VI, which were also separated from one another (with bootstrap values for branch separation higher than 60%).


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)

Maximum-likelihood DNA phylograms of S. enterica fimH and concatenated MLST loci (aroC, hisD and thrA).The fimH tree (A) was built based on an alignment of fimH sequences amplified from 55 isolates including 45 different strains of subspecies I and 10 strains of subspecies II–VI (for details see Table 1). Five additional alleles of fimH obtained from GenBank (S. Typhimurium AJB3 (Thm3), S. Typhimurium LB5010 (Thm4), S. Gallinarum 287/91 (Gal1) and 589/02 (Gal2), and S. Paratyphi C 49 [RKS4594] (PaC1) were included. The MLST loci tree (B) was built on an alignment of concatenated sequences of three genes (aroC, hisD and thrA) obtained for 57 study strains. The trees shown were rooted using S. enterica subsp. II (2993). The italicized values along the branches denote % bootstrap values based on 1000 runs (the bootstrap proportions along the terminal branches separating isolates within single serovars as well as the ones below 50% are not shown). Systemically invasive serovars are shown in red and non-invasive serovars are shown in black. Strain tags are as used in the text.
© Copyright Policy
Related In: Results  -  Collection

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

ppat-1002733-g001: Maximum-likelihood DNA phylograms of S. enterica fimH and concatenated MLST loci (aroC, hisD and thrA).The fimH tree (A) was built based on an alignment of fimH sequences amplified from 55 isolates including 45 different strains of subspecies I and 10 strains of subspecies II–VI (for details see Table 1). Five additional alleles of fimH obtained from GenBank (S. Typhimurium AJB3 (Thm3), S. Typhimurium LB5010 (Thm4), S. Gallinarum 287/91 (Gal1) and 589/02 (Gal2), and S. Paratyphi C 49 [RKS4594] (PaC1) were included. The MLST loci tree (B) was built on an alignment of concatenated sequences of three genes (aroC, hisD and thrA) obtained for 57 study strains. The trees shown were rooted using S. enterica subsp. II (2993). The italicized values along the branches denote % bootstrap values based on 1000 runs (the bootstrap proportions along the terminal branches separating isolates within single serovars as well as the ones below 50% are not shown). Systemically invasive serovars are shown in red and non-invasive serovars are shown in black. Strain tags are as used in the text.
Mentions: fimH was amplified from 55 of 56 S. enterica isolates, of which 45 represented 22 serovars of subspecies I, and 11 isolates represented other subspecies (Table 1). The isolate of S. enterica subsp. IIIa (2980) carried only part of the fimH gene and was excluded from further analysis. The maximum-likelihood phylogenetic tree constructed based on 55 amplified fimH sequences and five additional fimH alleles obtained from GenBank (fimH of S. Typhimurium AJB3 and LB5010, S. Gallinarum 287/91 and 589/02, and S. Paratyphi C 49 [RKS 4594]) is presented in Figure 1A. The fimH sequences of subspecies I (enterica) were grouped in a distinct phylogenetic clade separate from fimH of subspecies II–VI, which were also separated from one another (with bootstrap values for branch separation higher than 60%).

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