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Early emergence of Yersinia pestis as a severe respiratory pathogen.

Zimbler DL, Schroeder JA, Eddy JL, Lathem WW - Nat Commun (2015)

Bottom Line: Y. pestis recently evolved from the gastrointestinal pathogen Y. pseudotuberculosis; however, it is not known at what point Y. pestis gained the ability to induce a fulminant pneumonia.As Y. pestis further evolved, modern strains acquired a single amino-acid modification within Pla that optimizes protease activity.While this modification is unnecessary to cause pneumonic plague, the substitution is instead needed to efficiently induce the invasive infection associated with bubonic plague.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

ABSTRACT
Yersinia pestis causes the fatal respiratory disease pneumonic plague. Y. pestis recently evolved from the gastrointestinal pathogen Y. pseudotuberculosis; however, it is not known at what point Y. pestis gained the ability to induce a fulminant pneumonia. Here we show that the acquisition of a single gene encoding the protease Pla was sufficient for the most ancestral, deeply rooted strains of Y. pestis to cause pneumonic plague, indicating that Y. pestis was primed to infect the lungs at a very early stage in its evolution. As Y. pestis further evolved, modern strains acquired a single amino-acid modification within Pla that optimizes protease activity. While this modification is unnecessary to cause pneumonic plague, the substitution is instead needed to efficiently induce the invasive infection associated with bubonic plague. These findings indicate that Y. pestis was capable of causing pneumonic plague before it evolved to optimally cause invasive infections in mammals.

No MeSH data available.


Related in: MedlinePlus

pPCP1 is required by ancestral Y. pestis to cause primary pneumonic plague.(a) Genomic maximum parsimony tree and divergence based on 16 Y. pestis genomes. The division between modern, pandemic strains and ancestral isolates is indicated. Tree was adapted from Morelli et al.5 (b) Bacterial burden within the lungs and spleens of mice (n=10) infected i.n. with the indicated Y. pestis strains. Each point represents the numbers of bacteria recovered from a single mouse at 48 h post inoculation. The limit of detection is indicated by the dashed line and symbols in the dotted line indicate c.f.u. below the limit of detection. Symbols below the limit of detection represent mice that did not have detectable numbers of bacteria. A solid line indicates the median of c.f.u. recovered. The presence or absence of pPCP1 in each strain is indicated below. (c) Immunoblot analysis of whole-cell lysates of the indicated Y. pestis strains with antibodies to Pla and RpoA (as a loading control). The lower band represents the autoprocessed form of Pla (see Supplementary Fig. 5a). Full blots are shown in Supplementary Fig. 6. Panel is representative of three independent replicates. Data are combined from two independent experiments and error bars represent the s.e.m. (*P≤0.05, **P≤0.01, ***P≤0.001, NS, not significant by Mann–Whitney U-test).
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f1: pPCP1 is required by ancestral Y. pestis to cause primary pneumonic plague.(a) Genomic maximum parsimony tree and divergence based on 16 Y. pestis genomes. The division between modern, pandemic strains and ancestral isolates is indicated. Tree was adapted from Morelli et al.5 (b) Bacterial burden within the lungs and spleens of mice (n=10) infected i.n. with the indicated Y. pestis strains. Each point represents the numbers of bacteria recovered from a single mouse at 48 h post inoculation. The limit of detection is indicated by the dashed line and symbols in the dotted line indicate c.f.u. below the limit of detection. Symbols below the limit of detection represent mice that did not have detectable numbers of bacteria. A solid line indicates the median of c.f.u. recovered. The presence or absence of pPCP1 in each strain is indicated below. (c) Immunoblot analysis of whole-cell lysates of the indicated Y. pestis strains with antibodies to Pla and RpoA (as a loading control). The lower band represents the autoprocessed form of Pla (see Supplementary Fig. 5a). Full blots are shown in Supplementary Fig. 6. Panel is representative of three independent replicates. Data are combined from two independent experiments and error bars represent the s.e.m. (*P≤0.05, **P≤0.01, ***P≤0.001, NS, not significant by Mann–Whitney U-test).

Mentions: The adaptation of bacterial pathogens to new hosts and specific microenvironments within the body typically occurs via the combined gain and loss of genetic elements during the evolution of the species. Y. pestis, the causative agent of plague1, represents an exceptional system for understanding how a pathogen adapts to new host environments to cause disease due to its recent emergence as a human pathogen and its relatively clonal nature234. The divergence of Y. pestis from its progenitor species Y. pseudotuberculosis occurred within the last 10,000 years through multiple distinct genetic gains and losses, resulting in strikingly different modes of transmission and pathogenicity245. The soil- and water-borne enteropathogen Y. pseudotuberculosis causes the mild, self-limiting disease yersiniosis and is transmitted by the faecal–oral route1. In contrast, Y. pestis is transmitted by fleabites or aerosols, and causes the severely invasive and virulent disease plague1. Investigations on the genetic history of 118 annotated genomes of Y. pestis have revealed an evolutionary lineage that has defined both early ancestral (branch 0) and modern pandemic (branches 1 and 2) populations of Y. pestis6 based on sequential single-nucleotide polymorphism changes (Fig. 1a).


Early emergence of Yersinia pestis as a severe respiratory pathogen.

Zimbler DL, Schroeder JA, Eddy JL, Lathem WW - Nat Commun (2015)

pPCP1 is required by ancestral Y. pestis to cause primary pneumonic plague.(a) Genomic maximum parsimony tree and divergence based on 16 Y. pestis genomes. The division between modern, pandemic strains and ancestral isolates is indicated. Tree was adapted from Morelli et al.5 (b) Bacterial burden within the lungs and spleens of mice (n=10) infected i.n. with the indicated Y. pestis strains. Each point represents the numbers of bacteria recovered from a single mouse at 48 h post inoculation. The limit of detection is indicated by the dashed line and symbols in the dotted line indicate c.f.u. below the limit of detection. Symbols below the limit of detection represent mice that did not have detectable numbers of bacteria. A solid line indicates the median of c.f.u. recovered. The presence or absence of pPCP1 in each strain is indicated below. (c) Immunoblot analysis of whole-cell lysates of the indicated Y. pestis strains with antibodies to Pla and RpoA (as a loading control). The lower band represents the autoprocessed form of Pla (see Supplementary Fig. 5a). Full blots are shown in Supplementary Fig. 6. Panel is representative of three independent replicates. Data are combined from two independent experiments and error bars represent the s.e.m. (*P≤0.05, **P≤0.01, ***P≤0.001, NS, not significant by Mann–Whitney U-test).
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f1: pPCP1 is required by ancestral Y. pestis to cause primary pneumonic plague.(a) Genomic maximum parsimony tree and divergence based on 16 Y. pestis genomes. The division between modern, pandemic strains and ancestral isolates is indicated. Tree was adapted from Morelli et al.5 (b) Bacterial burden within the lungs and spleens of mice (n=10) infected i.n. with the indicated Y. pestis strains. Each point represents the numbers of bacteria recovered from a single mouse at 48 h post inoculation. The limit of detection is indicated by the dashed line and symbols in the dotted line indicate c.f.u. below the limit of detection. Symbols below the limit of detection represent mice that did not have detectable numbers of bacteria. A solid line indicates the median of c.f.u. recovered. The presence or absence of pPCP1 in each strain is indicated below. (c) Immunoblot analysis of whole-cell lysates of the indicated Y. pestis strains with antibodies to Pla and RpoA (as a loading control). The lower band represents the autoprocessed form of Pla (see Supplementary Fig. 5a). Full blots are shown in Supplementary Fig. 6. Panel is representative of three independent replicates. Data are combined from two independent experiments and error bars represent the s.e.m. (*P≤0.05, **P≤0.01, ***P≤0.001, NS, not significant by Mann–Whitney U-test).
Mentions: The adaptation of bacterial pathogens to new hosts and specific microenvironments within the body typically occurs via the combined gain and loss of genetic elements during the evolution of the species. Y. pestis, the causative agent of plague1, represents an exceptional system for understanding how a pathogen adapts to new host environments to cause disease due to its recent emergence as a human pathogen and its relatively clonal nature234. The divergence of Y. pestis from its progenitor species Y. pseudotuberculosis occurred within the last 10,000 years through multiple distinct genetic gains and losses, resulting in strikingly different modes of transmission and pathogenicity245. The soil- and water-borne enteropathogen Y. pseudotuberculosis causes the mild, self-limiting disease yersiniosis and is transmitted by the faecal–oral route1. In contrast, Y. pestis is transmitted by fleabites or aerosols, and causes the severely invasive and virulent disease plague1. Investigations on the genetic history of 118 annotated genomes of Y. pestis have revealed an evolutionary lineage that has defined both early ancestral (branch 0) and modern pandemic (branches 1 and 2) populations of Y. pestis6 based on sequential single-nucleotide polymorphism changes (Fig. 1a).

Bottom Line: Y. pestis recently evolved from the gastrointestinal pathogen Y. pseudotuberculosis; however, it is not known at what point Y. pestis gained the ability to induce a fulminant pneumonia.As Y. pestis further evolved, modern strains acquired a single amino-acid modification within Pla that optimizes protease activity.While this modification is unnecessary to cause pneumonic plague, the substitution is instead needed to efficiently induce the invasive infection associated with bubonic plague.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.

ABSTRACT
Yersinia pestis causes the fatal respiratory disease pneumonic plague. Y. pestis recently evolved from the gastrointestinal pathogen Y. pseudotuberculosis; however, it is not known at what point Y. pestis gained the ability to induce a fulminant pneumonia. Here we show that the acquisition of a single gene encoding the protease Pla was sufficient for the most ancestral, deeply rooted strains of Y. pestis to cause pneumonic plague, indicating that Y. pestis was primed to infect the lungs at a very early stage in its evolution. As Y. pestis further evolved, modern strains acquired a single amino-acid modification within Pla that optimizes protease activity. While this modification is unnecessary to cause pneumonic plague, the substitution is instead needed to efficiently induce the invasive infection associated with bubonic plague. These findings indicate that Y. pestis was capable of causing pneumonic plague before it evolved to optimally cause invasive infections in mammals.

No MeSH data available.


Related in: MedlinePlus