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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

The ancestral variant of Pla is sufficient to cause pneumonic plague but not optimal systemic infection.(a) Bacterial burden within the lungs and spleens of mice (n=10) infected i.n. with Y. pestis CO92 or Pestoides F carrying pPCP1 with either the T259 or I259 variant of Pla, as described in Fig. 1. (b) Bacterial burden within the inguinal lymph nodes and spleens of s.c. infected mice (n=10) with wild-type Pestoides F, or CO92 or Pestoides F carrying pPCP1 with either the T259 or I259 variant of Pla. The variant of Pla in each strain is indicated. Data are combined from two independent experiments and error bars represent the s.e.m. (*P≤0.05, NS, not significant by Mann–Whitney U-test).
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f5: The ancestral variant of Pla is sufficient to cause pneumonic plague but not optimal systemic infection.(a) Bacterial burden within the lungs and spleens of mice (n=10) infected i.n. with Y. pestis CO92 or Pestoides F carrying pPCP1 with either the T259 or I259 variant of Pla, as described in Fig. 1. (b) Bacterial burden within the inguinal lymph nodes and spleens of s.c. infected mice (n=10) with wild-type Pestoides F, or CO92 or Pestoides F carrying pPCP1 with either the T259 or I259 variant of Pla. The variant of Pla in each strain is indicated. Data are combined from two independent experiments and error bars represent the s.e.m. (*P≤0.05, NS, not significant by Mann–Whitney U-test).

Mentions: We next asked whether the T259 variant of Pla enhances virulence during primary pneumonic plague compared with the Pla I259 in either the modern (CO92) or ancestral (Pestoides F) strains of Y. pestis by assessing the bacterial burden in the lungs after 48 h. We found no significant difference (Mann–Whitney U-test) in c.f.u. in the lungs of Pestoides F or CO92 expressing the I259 variant of Pla compared with the same strains expressing Pla T259 (Fig. 5a), indicating that this single amino-acid substitution was not required for Y. pestis to infect the lungs and rapidly replicate. However, there were significantly fewer bacteria in the spleens of mice infected with Pla I259 compared with the T259 variant in the Pestoides F isolate (Fig. 5a). Together with the data presented in Fig. 4, our results indicate that once Y. pestis acquired Pla, no additional genetic changes were required for the plague bacillus to cause a rapidly progressing pneumonic infection; rather this modification may instead be involved in dissemination from the lungs and/or bacterial survival during systemic infection.


Early emergence of Yersinia pestis as a severe respiratory pathogen.

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

The ancestral variant of Pla is sufficient to cause pneumonic plague but not optimal systemic infection.(a) Bacterial burden within the lungs and spleens of mice (n=10) infected i.n. with Y. pestis CO92 or Pestoides F carrying pPCP1 with either the T259 or I259 variant of Pla, as described in Fig. 1. (b) Bacterial burden within the inguinal lymph nodes and spleens of s.c. infected mice (n=10) with wild-type Pestoides F, or CO92 or Pestoides F carrying pPCP1 with either the T259 or I259 variant of Pla. The variant of Pla in each strain is indicated. Data are combined from two independent experiments and error bars represent the s.e.m. (*P≤0.05, NS, not significant by Mann–Whitney U-test).
© Copyright Policy - open-access
Related In: Results  -  Collection

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f5: The ancestral variant of Pla is sufficient to cause pneumonic plague but not optimal systemic infection.(a) Bacterial burden within the lungs and spleens of mice (n=10) infected i.n. with Y. pestis CO92 or Pestoides F carrying pPCP1 with either the T259 or I259 variant of Pla, as described in Fig. 1. (b) Bacterial burden within the inguinal lymph nodes and spleens of s.c. infected mice (n=10) with wild-type Pestoides F, or CO92 or Pestoides F carrying pPCP1 with either the T259 or I259 variant of Pla. The variant of Pla in each strain is indicated. Data are combined from two independent experiments and error bars represent the s.e.m. (*P≤0.05, NS, not significant by Mann–Whitney U-test).
Mentions: We next asked whether the T259 variant of Pla enhances virulence during primary pneumonic plague compared with the Pla I259 in either the modern (CO92) or ancestral (Pestoides F) strains of Y. pestis by assessing the bacterial burden in the lungs after 48 h. We found no significant difference (Mann–Whitney U-test) in c.f.u. in the lungs of Pestoides F or CO92 expressing the I259 variant of Pla compared with the same strains expressing Pla T259 (Fig. 5a), indicating that this single amino-acid substitution was not required for Y. pestis to infect the lungs and rapidly replicate. However, there were significantly fewer bacteria in the spleens of mice infected with Pla I259 compared with the T259 variant in the Pestoides F isolate (Fig. 5a). Together with the data presented in Fig. 4, our results indicate that once Y. pestis acquired Pla, no additional genetic changes were required for the plague bacillus to cause a rapidly progressing pneumonic infection; rather this modification may instead be involved in dissemination from the lungs and/or bacterial survival during systemic infection.

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