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Antimicrob Agents Chemother. Natural History of Yersinia pestis Pneumonia in Aerosol-Challenged BALB/c Mice
[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]
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Natural History of Yersinia pestis Pneumonia in Aerosol-Challenged BALB/c Mice
Henry S. Heine, Ph.D.1, Lara Chuvala, M.S.1, Renaldo Riggins, B.S.1, Gregory Hurteau, B.S.1, Ryan Cirz, Ph.D.2, Robert Cass, B.S.2, Arnold Louie, M.D.1 and G.L. Drusano, M.D.1
Author Affiliations: <SUP>1</SUP>Institute for Therapeutic Innovation, Department of Medicine, University of Florida, School of Medicine, 150 New Scotland Avenue, Albany NY 12208 <SUP>2</SUP>Achaogen, Inc., 7000 Shoreline Court, Suite 371, South San Francisco, CA 94080
ABSTRACT
After a relatively short untreated interval, pneumonic plague has a mortality approaching 100%. We employed a murine model of aerosol challenge with Y. pestis to investigate the early course of pneumonic plague in lung, blood and spleen. We fit a mathematical model to all data simultaneously. The model fit to the data was acceptable. The number of organisms in the lung at baseline was estimated at 135 (median) ? 1184 (mean) CFU/g. Doubling time was estimated at 1.5-1.7 hr. Between hrs 1and 12 post-exposure, counts declined, but then increased by hr 24, a finding hypothesized to be due to innate immunity. The model predicted that innate immunity declined with a half-time of 3-3.8 hr. The threshold for bacteremia was 6.4?10<SUP>4</SUP> to 1.52?10<SUP>6</SUP> CFU/g. By 42-48 hr, stationary phase was obtained. Lung bacterial burdens exceeded 10 Logs/g. Obviating early defenses allows rapid amplification of Y. pestis with bacteremia, making the rapid course with high mortality understandable.
FOOTNOTES
Corresponding Author: Henry S. Heine, Ph.D. Program Director, Select Agent Studies, Institute for Therapeutic Innovation, Department of Medicine, University of Florida, (407) 313 7062 (Telephone). Henry.Heine@medicine.ufl.edu University of Florida
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
-Henry S. Heine, Ph.D.1, Lara Chuvala, M.S.1, Renaldo Riggins, B.S.1, Gregory Hurteau, B.S.1, Ryan Cirz, Ph.D.2, Robert Cass, B.S.2, Arnold Louie, M.D.1 and G.L. Drusano, M.D.1
Author Affiliations: <SUP>1</SUP>Institute for Therapeutic Innovation, Department of Medicine, University of Florida, School of Medicine, 150 New Scotland Avenue, Albany NY 12208 <SUP>2</SUP>Achaogen, Inc., 7000 Shoreline Court, Suite 371, South San Francisco, CA 94080
ABSTRACT
After a relatively short untreated interval, pneumonic plague has a mortality approaching 100%. We employed a murine model of aerosol challenge with Y. pestis to investigate the early course of pneumonic plague in lung, blood and spleen. We fit a mathematical model to all data simultaneously. The model fit to the data was acceptable. The number of organisms in the lung at baseline was estimated at 135 (median) ? 1184 (mean) CFU/g. Doubling time was estimated at 1.5-1.7 hr. Between hrs 1and 12 post-exposure, counts declined, but then increased by hr 24, a finding hypothesized to be due to innate immunity. The model predicted that innate immunity declined with a half-time of 3-3.8 hr. The threshold for bacteremia was 6.4?10<SUP>4</SUP> to 1.52?10<SUP>6</SUP> CFU/g. By 42-48 hr, stationary phase was obtained. Lung bacterial burdens exceeded 10 Logs/g. Obviating early defenses allows rapid amplification of Y. pestis with bacteremia, making the rapid course with high mortality understandable.
FOOTNOTES
Corresponding Author: Henry S. Heine, Ph.D. Program Director, Select Agent Studies, Institute for Therapeutic Innovation, Department of Medicine, University of Florida, (407) 313 7062 (Telephone). Henry.Heine@medicine.ufl.edu University of Florida
Copyright ? 2013, American Society for Microbiology. All Rights Reserved.
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