Progression of primary pneumonic plague: a mouse model of infection, pathology, and bacterial transcriptional activity.
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.
Lathem
Wyndham W
WW
Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Crosby
Seth D
SD
Miller
Virginia L
VL
Goldman
William E
WE
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
D016207:Cytokines; D012333:RNA, Messenger