title: Progression of primary pneumonic plague: a mouse model of infection, pathology, and bacterial transcriptional activity.
abstract: Although pneumonic plague is the deadliest manifestation of disease caused by the bacterium Yersinia pestis, there is surprisingly little information on the cellular and molecular mechanisms responsible for Y. pestis-triggered pathology in the lung. Therefore, to understand the progression of this unique disease, we characterized an intranasal mouse model of primary pneumonic plague. Mice succumbed to a purulent multifocal severe exudative bronchopneumonia that closely resembles the disease observed in humans. Analyses revealed a strikingly biphasic syndrome, in which the infection begins with an antiinflammatory state in the first 24-36 h that rapidly progresses to a highly proinflammatory state by 48 h and death by 3 days. To assess the adaptation of Y. pestis to a mammalian environment, we used DNA microarray technology to analyze the transcriptional responses of the bacteria during interaction with the mouse lung. Included among the genes up-regulated in vivo are those comprising the yop-ysc type III secretion system and genes contained within the chromosomal pigmentation locus, validating the use of this technology to identify loci essential to the virulence of Y. pestis.
authors.affiliation: Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
authors.forename: Wyndham W
authors.initials: WW
authors.lastname: Lathem
authors.forename: Seth D
authors.initials: SD
authors.lastname: Crosby
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Miller
authors.forename: William E
authors.initials: WE
authors.lastname: Goldman
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D010930:Plague / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D015996:Survival Rate; D014158:Transcription, Genetic / Q000235:genetics*; D015010:Yersinia pestis / Q000235:genetics* / Q000502:physiology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger