TY - JOUR
T1 - Characterization of the rat pneumonic plague model
T2 - infection kinetics following aerosolization of Yersinia pestis CO92
AU - Agar, Stacy L.
AU - Sha, Jian
AU - Foltz, Sheri M.
AU - Erova, Tatiana E.
AU - Walberg, Kristin G.
AU - Baze, Wallace B.
AU - Suarez, Giovanni
AU - Peterson, Johnny W.
AU - Chopra, Ashok K.
N1 - Funding Information:
This research was supported by NIH/NIAID grants N01-AI-30065 and AI064389. We thank Dr. Kristin DeBord, Program Office, NIH/NIAID, in helping us to initiate plague studies using the rat model. SLA is a pre-doctoral fellow supported by the NIAID T32 Emerging and Tropical Infectious Diseases (AI07526) and Biodefense (AI060549) training grants. We thank Ms. Mardelle Susman for her careful review of the manuscript.
PY - 2009/2
Y1 - 2009/2
N2 - Yersinia pestis, the causative agent of human bubonic and pneumonic plague, is spread during natural infection by the fleas of rodents. Historically associated with infected rat fleas, studies on the kinetics of infection in rats are surprisingly few, and these reports have focused mainly on bubonic plague. Although the natural route of primary infection results in bubonic plague in humans, it is commonly thought that aerosolized Y. pestis will be utilized during a biowarfare attack. Accordingly, based on our previous characterization of the mouse model of pneumonic plague, we sought to examine the progression of infection in rats exposed in a whole-body Madison chamber to aerosolized Y. pestis CO92. Following an 8.6 LD50 dose of Y. pestis, injury was apparent in the rat tissues based on histopathology, and chemokines and cytokines rose above control levels (1 h post infection [p.i.]) in the sera and organ homogenates over a 72-h infection period. Bacteria disseminated from the lungs to peripheral organs, with the largest increases in the spleen, followed by the liver and blood at 72 h p.i. compared to the 1 h controls. Importantly, rats were as sensitive to pneumonic plague as mice, having a similar LD50 dose by the intranasal and aerosolized routes. Further, we showed direct transmission of plague bacteria from infected to uninfected rats. Taken together, the data allowed us to characterize for the first time a rat pneumonic plague model following aerosolization of Y. pestis.
AB - Yersinia pestis, the causative agent of human bubonic and pneumonic plague, is spread during natural infection by the fleas of rodents. Historically associated with infected rat fleas, studies on the kinetics of infection in rats are surprisingly few, and these reports have focused mainly on bubonic plague. Although the natural route of primary infection results in bubonic plague in humans, it is commonly thought that aerosolized Y. pestis will be utilized during a biowarfare attack. Accordingly, based on our previous characterization of the mouse model of pneumonic plague, we sought to examine the progression of infection in rats exposed in a whole-body Madison chamber to aerosolized Y. pestis CO92. Following an 8.6 LD50 dose of Y. pestis, injury was apparent in the rat tissues based on histopathology, and chemokines and cytokines rose above control levels (1 h post infection [p.i.]) in the sera and organ homogenates over a 72-h infection period. Bacteria disseminated from the lungs to peripheral organs, with the largest increases in the spleen, followed by the liver and blood at 72 h p.i. compared to the 1 h controls. Importantly, rats were as sensitive to pneumonic plague as mice, having a similar LD50 dose by the intranasal and aerosolized routes. Further, we showed direct transmission of plague bacteria from infected to uninfected rats. Taken together, the data allowed us to characterize for the first time a rat pneumonic plague model following aerosolization of Y. pestis.
KW - Pneumonic plague
KW - Rat model of infection
KW - Yersinia pestis
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UR - http://www.scopus.com/inward/citedby.url?scp=61449193110&partnerID=8YFLogxK
U2 - 10.1016/j.micinf.2008.11.009
DO - 10.1016/j.micinf.2008.11.009
M3 - Article
C2 - 19073275
AN - SCOPUS:61449193110
SN - 1286-4579
VL - 11
SP - 205
EP - 214
JO - Microbes and Infection
JF - Microbes and Infection
IS - 2
ER -