Progression of primary pneumonic plague: a mouse model of infection, pathology, and bacterial transcriptional
Wyndham W Lathem1, Seth D Crosby, Virginia L Miller
1Department of Molecular Microbiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
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.
Insights
Pneumonic plague, caused by Yersinia pestis, involves an anti-inflammatory phase followed by a severe pro-inflammatory response. This study identifies key bacterial genes essential for Yersinia pestis virulence in the lung.
Area of Science:
- Microbiology
- Pathology
- Immunology
Background:
- Pneumonic plague, a severe Yersinia pestis infection, lacks detailed understanding of lung pathology mechanisms.
- Yersinia pestis virulence factors are crucial for disease progression.
Purpose of the Study:
- To characterize an intranasal mouse model of primary pneumonic plague.
- To investigate Yersinia pestis transcriptional responses during lung infection.
Main Methods:
- Intranasal inoculation of mice to establish pneumonic plague.
- DNA microarray analysis of Yersinia pestis gene expression in vivo.
- Histopathological examination of lung tissues.
Main Results:
- The mouse model exhibited purulent, exudative bronchopneumonia similar to human disease.
- A biphasic inflammatory response was observed: initial anti-inflammation (24-36h) followed by intense pro-inflammation (48h).
- Yersinia pestis up-regulated genes included the yop-ysc type III secretion system and pigmentation locus.
Conclusions:
- The developed mouse model accurately mimics human pneumonic plague.
- Yersinia pestis exhibits a biphasic inflammatory response during lung infection.
- Type III secretion system and pigmentation genes are critical for Yersinia pestis virulence in vivo.
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