Attenuation of virulence in <i>Yersinia pestis</i> across three plague pandemics
<i>Yersinia pestis</i> has spilled over from wild rodent reservoirs to commensal rodents and humans, causing three historically recorded pandemics. Depletion in the copy number of the plasmid-encoded virulence gene <i>pla</i> occurred in later-dated strains of the first and second pandemics, yet the biological relevance of the <i>pla</i> deletion has been difficult to test. We identified modern <i>Y. pestis</i> strains that independently acquired the same <i>pla</i> depletion as ancient strains and herein show that excision of <i>pla</i> from the multicopy pPCP1 plasmid is accompanied by the integration of a separate full pPCP1 harboring <i>pla</i> into the single-copy pCD1 plasmid, reducing <i>pla</i> dosage. Moreover, we demonstrate that this depletion decreases the mortality of mice in models of bubonic plague but not in the pneumonic and septicemic forms of the disease. We hypothesize that <i>pla</i> depletion may have been selectively advantageous in bubonic plague, owing to rodent fragmentation after pandemic-induced mortality.
Authors
- Pierre Lê-Bury (ORCID: https://orcid.org/0000-0002-6010-2952)
- Daniel J. Salkeld (ORCID: https://orcid.org/0000-0002-1272-0721)
- Aurélia Kwasiborski (ORCID: https://orcid.org/0000-0003-0826-613X)
- Nicolás Rascovan (ORCID: https://orcid.org/0000-0002-2129-5878)
- Ravneet Kaur Sidhu (ORCID: https://orcid.org/0000-0001-6377-5987)
- Benjamin M. Bolker (ORCID: https://orcid.org/0000-0002-2127-0443)
- Jennifer Klunk (ORCID: https://orcid.org/0000-0002-6521-8516)
- Guillem Mas Fiol (ORCID: https://orcid.org/0000-0002-4024-3002)
- Javier Pizarro‐Cerdá (ORCID: https://orcid.org/0000-0002-4343-0508)
- Hendrik N. Poinar (ORCID: https://orcid.org/0000-0002-0314-4160)
- Nükhet Varlık (ORCID: https://orcid.org/0000-0001-6870-5945)
- G. Brian Golding (ORCID: https://orcid.org/0000-0002-7575-0282)
- Charlotte Balière (ORCID: https://orcid.org/0000-0002-2865-5493)
- Debi Poinar
- Christian E. Demeure (ORCID: https://orcid.org/0000-0001-7195-1645)
- Olivier Dussurget (ORCID: https://orcid.org/0000-0001-9924-0837)
- Ann G. Carmichael (ORCID: https://orcid.org/0000-0001-7516-7460)
- Valérie Caro (ORCID: https://orcid.org/0000-0001-8477-5708)
- Jonathan Dushoff (ORCID: https://orcid.org/0000-0003-0506-4794)
- David J. D. Earn (ORCID: https://orcid.org/0000-0002-7562-1341)
- Edward C. Holmes (ORCID: https://orcid.org/0000-0001-9596-3552)
- Rémi Beau (ORCID: https://orcid.org/0000-0002-8663-6688)
- Emelyne Bougit
Institutions
- Rutgers, The State University of New Jersey (US)
- Canadian Institute for Advanced Research (CA)
- The University of Sydney (AU)
- Inserm (FR)
- Institut Pasteur (FR)
- Université Paris Cité (FR)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- McMaster University Medical Centre (CA)
- Indiana University Bloomington (US)
- CEA Paris-Saclay (FR)
- Infectious Disease Models and Innovative Therapies (FR)
- Colorado State University (US)
- McMaster University (CA)
Publication Details
- Journal
- Science
- Published
- 2025-05-29
- DOI
- https://doi.org/10.1126/science.adt3880
- Citations
- 12
- Primary Topic
- Yersinia bacterium, plague, ectoparasites research
- Type
- article
- Field-Weighted Citation Impact
- 21.81