Attenuation of virulence in Yersinia pestis across three plague pandemics

• 成果类型: Article
• 署名作者: Sidhu, Ravneet Kaur; Mas Fiol, Guillem; Le-Bury, Pierre; Demeure, Christian E.; Bougit, Emelyne; Beau, Remi; Baliere, Charlotte; Kwasiborski, Aurelia; Caro, Valerie; Klunk, Jennifer; Salkeld, Daniel J.; Carmichael, Ann; Varlik, Nuekhet; Poinar, Debi; Earn, David J. D.; Bolker, Benjamin M.; Dushoff, Jonathan; Golding, G. Brian; Rascovan, Nicolas; Dussurget, Olivier; Holmes, Edward C.; Pizarro-Cerda, Javier; Poinar, Hendrik N.
• 署名单位: McMaster University; McMaster University; McMaster University; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Universite Paris Saclay; Institut National de la Sante et de la Recherche Medicale (Inserm); CEA; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; Colorado State University System; Colorado State University Fort Collins; Indiana University System; Indiana University Bloomington; Rutgers University System; Rutgers University New Brunswick; Rutgers University Newark; McMaster University; McMaster University; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris; University of Sydney; Canadian Institute for Advanced Research (CIFAR)
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10325
• DOI: 10.1126/science.adt3880
• 发表日期: 2025-05-29
• 关键词: bubonic plague; rattus-rattus; EVOLUTION; metapopulation; infection; sequence; protease; ancient; susceptibility; persistence

摘要

Yersinia pestis 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 pla occurred in later-dated strains of the first and second pandemics, yet the biological relevance of the pla deletion has been difficult to test. We identified modern Y. pestis strains that independently acquired the same pla depletion as ancient strains and herein show that excision of pla from the multicopy pPCP1 plasmid is accompanied by the integration of a separate full pPCP1 harboring pla into the single-copy pCD1 plasmid, reducing pla 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 pla depletion may have been selectively advantageous in bubonic plague, owing to rodent fragmentation after pandemic-induced mortality.