Early emergence of Yersinia pestis as a severe respiratory pathogen

Daniel L. Zimbler, Jay A. Schroeder, Justin L. Eddy, Wyndham W. Lathem*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

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.

Original languageEnglish (US)
Article number7487
JournalNature communications
Volume6
DOIs
StatePublished - Jun 30 2015

Funding

This work was supported by funding from Public Health Grants R01 AI093727 and R21 AI103658 to W.W.L. D.L.Z. was supported by funding from T32 AI007476. We thank Jeremy Ritzert, Lauren Bellows, Danielle O’Neal and Dr Adam Caulfield for technical assistance, and Dr Paul Keim for helpful discussions. We are grateful to Dr Susan Straley for providing the pPCP1::kan plasmid, Dr Robert Perry for providing the pCD1Ap plasmid, Y. pestis Angola, Pestoides A and E strains, and Dr Scott Bearden for providing the Y. pestis Pestoides F strain. This work was supported by the Northwestern University Interdepartmental Immunobiology Flow Cytometry Core Facility. Histopathology was performed by the Northwestern University Mouse Histology and Phenotyping Laboratory, supported by NCI CA060553. Imaging was performed at the Northwestern University Cell Imaging Facility, supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center.

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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