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 u...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-12, Vol.102 (49), p.17786-17791
Main Authors: Wyndham W. Lathem, Crosby, Seth D., Miller, Virginia L., Goldman, William E.
Format: Article
Language:English
Subjects:
Animals
Arrays
Bacteria
Biological Sciences
Cytokines
Cytokines - biosynthesis
Disease Models, Animal
Disease Progression
Female
Gene Expression Regulation, Bacterial
Genes
Humans
Infections
Kinetics
Lungs
Mice
Mice, Inbred C57BL
Microbiology
Oligonucleotide Array Sequence Analysis
Pathology
Plague
Plague - metabolism
Plague - microbiology
Plague - pathology
Pneumonia
Pneumonic plague
Pulmonary alveoli
RNA
RNA, Messenger - genetics
Rodents
Spleen
Survival Rate
Transcription, Genetic - genetics
Yersinia pestis
Yersinia pestis - genetics
Yersinia pestis - physiology
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0506840102