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Title: An integrated experimental-computational approach for predicting virulence in New Zealand white rabbits and humans following inhalation exposure to Bacillus anthracis spores

Abstract

Inhalation of Bacillus anthracis spores can lead to an anthrax infection that can be fatal. Previously published mathematical models have extrapolated kinetic rates associated with bacterial growth in New Zealand White (NZW) rabbits to humans, but to date, actual measurements of the underlying processes associated with anthrax virulence between species have not been conducted. To address this knowledge gap, we have quantified species-specific rate constants associated with germination, proliferation, and immune cell inactivation of B. anthracis Sterne using an in vitro test platform that includes primary lung epithelial and immune cells. The generated data was then used to develop a physiologically based biokinetic model (PBBK) which quantitatively compares bacterial growth and mean time to death under lethal conditions in rabbits and humans. Simulations based upon our in vitro data and previously published in vivo data from rabbits indicate that disease progression is likely to be faster in humans than in NZW rabbits under comparable total deposited dose conditions. With the computational framework established, PBBK parameters can now be refined using experimental data for lethal B. anthracis strains (e.g. Ames) under identical conditions in future studies. The PBBK model can also be linked to existing aerosol dosimetry models that account formore » species-specific differences in aerosol deposition patterns to further improve the human health risk assessment of inhalation anthrax.« less

Authors:
ORCiD logo [1];  [1];  [1];  [1];  [1];  [1];  [2];  [3];  [4];  [5]
  1. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States); USDA-ARS National Animal Disease Center, Ames, IA (United States)
  3. Pacific Northwest National Lab. (PNNL), Richland, WA (United States); EMD Serono, Billerica, MA (United States)
  4. Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Greek Creek Toxicokinetics Consulting, LLC, Boise, ID (United States)
  5. Laurentian (Canada)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1557676
Alternate Identifier(s):
OSTI ID: 1576229
Report Number(s):
PNNL-SA-140673
Journal ID: ISSN 1932-6203
Grant/Contract Number:  
HSHQPM-14-X-00037; AC05-76RL01830
Resource Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 14; Journal Issue: 7; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; 3-D tissue culture, B. anthracis Sterne, biothreats, computational model

Citation Formats

Hess, Becky M., Thomas, Dennis G., Weber, Thomas J., Hutchison, Janine R., Straub, Timothy M., Bruckner-Lea, Cynthia J., Powell, Joshua D., Kabilan, Senthil, Corley, Richard A., and Omri, Abdelwahab. An integrated experimental-computational approach for predicting virulence in New Zealand white rabbits and humans following inhalation exposure to Bacillus anthracis spores. United States: N. p., 2019. Web. doi:10.1371/journal.pone.0219160.
Hess, Becky M., Thomas, Dennis G., Weber, Thomas J., Hutchison, Janine R., Straub, Timothy M., Bruckner-Lea, Cynthia J., Powell, Joshua D., Kabilan, Senthil, Corley, Richard A., & Omri, Abdelwahab. An integrated experimental-computational approach for predicting virulence in New Zealand white rabbits and humans following inhalation exposure to Bacillus anthracis spores. United States. doi:10.1371/journal.pone.0219160.
Hess, Becky M., Thomas, Dennis G., Weber, Thomas J., Hutchison, Janine R., Straub, Timothy M., Bruckner-Lea, Cynthia J., Powell, Joshua D., Kabilan, Senthil, Corley, Richard A., and Omri, Abdelwahab. Mon . "An integrated experimental-computational approach for predicting virulence in New Zealand white rabbits and humans following inhalation exposure to Bacillus anthracis spores". United States. doi:10.1371/journal.pone.0219160. https://www.osti.gov/servlets/purl/1557676.
@article{osti_1557676,
title = {An integrated experimental-computational approach for predicting virulence in New Zealand white rabbits and humans following inhalation exposure to Bacillus anthracis spores},
author = {Hess, Becky M. and Thomas, Dennis G. and Weber, Thomas J. and Hutchison, Janine R. and Straub, Timothy M. and Bruckner-Lea, Cynthia J. and Powell, Joshua D. and Kabilan, Senthil and Corley, Richard A. and Omri, Abdelwahab},
abstractNote = {Inhalation of Bacillus anthracis spores can lead to an anthrax infection that can be fatal. Previously published mathematical models have extrapolated kinetic rates associated with bacterial growth in New Zealand White (NZW) rabbits to humans, but to date, actual measurements of the underlying processes associated with anthrax virulence between species have not been conducted. To address this knowledge gap, we have quantified species-specific rate constants associated with germination, proliferation, and immune cell inactivation of B. anthracis Sterne using an in vitro test platform that includes primary lung epithelial and immune cells. The generated data was then used to develop a physiologically based biokinetic model (PBBK) which quantitatively compares bacterial growth and mean time to death under lethal conditions in rabbits and humans. Simulations based upon our in vitro data and previously published in vivo data from rabbits indicate that disease progression is likely to be faster in humans than in NZW rabbits under comparable total deposited dose conditions. With the computational framework established, PBBK parameters can now be refined using experimental data for lethal B. anthracis strains (e.g. Ames) under identical conditions in future studies. The PBBK model can also be linked to existing aerosol dosimetry models that account for species-specific differences in aerosol deposition patterns to further improve the human health risk assessment of inhalation anthrax.},
doi = {10.1371/journal.pone.0219160},
journal = {PLoS ONE},
number = 7,
volume = 14,
place = {United States},
year = {2019},
month = {7}
}

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