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A comprehensive study on the role of the <Emphasis Type="Italic">Yersinia pestis</Emphasis> virulence markers in an animal model of pneumonic plague
Authors:W E Kaman  D van der Kleij  M P Broekhuijsen  N J Silman  F J Bikker
Institution:(1) TNO Defence, Security and Safety, 2280 AA Rijswijk, the Netherlands;(2) Department of Medical Microbiology and Infectious Diseases, Erasmus MC, 3015 Rotterdam, the Netherlands;(3) Research Department, Centre for Emergency Preparedness and Response, Health Protection Agency, Porton Down, SP4 0JG Salisbury, UK;(4) Department of Oral Biochemistry, Academic Centre for Dentistry Amsterdam, University of Amsterdam, Amsterdam, the Netherlands;(5) VU University Amsterdam, 1081LA Amsterdam, the Netherlands;(6) Department of Medical Microbiology and Infectious Diseases, Erasmus MC, ‘s-Gravendijkwal 230, 3015 Rotterdam, the Netherlands
Abstract:We determined the role of Yersinia pestis virulence markers in an animal model of pneumonic plague. Eleven strains of Y. pestis were characterized using PCR assays to detect the presence of known virulence genes both encoded by the three plasmids as well as chromosomal markers. The virulence of all Y. pestis strains was compared in a mouse model for pneumonic plague. The presence of all known virulence genes correlated completely with virulence in the Balb/c mouse model. Strains which lacked HmsF initially exhibited visible signs of disease whereas all other strains (except wild-type strains) did not exhibit any disease signs. Forty-eight hours post-infection, mice which had received HmsF strains regained body mass and were able to control infection; those infected with strains possessing a full complement of virulence genes suffered from fatal disease. The bacterial loads observed in the lung and other tissues reflected the observed clinical signs as did the cytokine changes measured in these animals. We can conclude that all known virulence genes are required for the establishment of pneumonic plague in mammalian animal models, the role of HmsF being of particular importance in disease progression.
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