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Early emergence of Yersinia pestis as a severe respiratory pathogen
Daniel L Zimbler1, Jay A Schroeder1, Justin L Eddy1
1Department 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.
Insights
The acquisition of the Pla gene enabled early Yersinia pestis strains to cause pneumonic plague. Later evolution optimized Pla for bubonic plague, not pneumonia.
Area of Science:
- Microbiology
- Evolutionary Biology
- Pathogen Dynamics
Background:
- Yersinia pestis is a bacterium responsible for the deadly pneumonic plague.
- The pathogen evolved from Yersinia pseudotuberculosis, a gastrointestinal bacterium.
- The evolutionary step at which Y. pestis acquired the ability to cause pneumonia remains unclear.
Purpose of the Study:
- To determine the genetic basis for Y. pestis's ability to cause pneumonic plague.
- To investigate the role of the protease Pla in the evolution of Y. pestis virulence.
- To understand the distinct evolutionary pathways leading to pneumonic and bubonic plague.
Main Methods:
- Comparative genomics analysis of Yersinia species.
- Experimental evolution studies.
- In vitro and in vivo virulence assays.
Main Results:
- The acquisition of the single gene encoding the protease Pla was sufficient for ancestral Y. pestis strains to cause pneumonic plague.
- A single amino-acid modification in Pla, acquired later in evolution, optimizes protease activity.
- This modification is crucial for the invasive infections characteristic of bubonic plague, but not for causing pneumonia.
Conclusions:
- Yersinia pestis possessed the capability for causing pneumonic plague early in its evolutionary history.
- The Pla protease played a pivotal role in the initial emergence of pneumonic plague.
- Later adaptations in Pla enhanced virulence for bubonic plague, indicating distinct evolutionary pressures.
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