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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

Journal Article · · PLoS ONE
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)
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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 genereated 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.

Research Organization:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
HSHQPM-14-X-00037; AC05-76RL01830
OSTI ID:
1557676
Alternate ID(s):
OSTI ID: 1576229
Report Number(s):
PNNL-SA-140673
Journal Information:
PLoS ONE, Vol. 14, Issue 7; ISSN 1932-6203
Publisher:
Public Library of ScienceCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 3 works
Citation information provided by
Web of Science

References (14)

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Alveolar epithelium protects macrophages from quorum sensing-induced cytotoxicity in a three-dimensional co-culture model: Quorum sensing effects in an alveolar tissue model journal November 2010
Bacillus anthracis physiology and genetics journal December 2009
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Molecular pathogenesis of Bacillus anthracis infection journal February 1999

Cited By (1)

Ventilation Modulation and Nanoparticle Deposition in Respiratory and Olfactory Regions of Rabbit Nose journal December 2019

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60 APPLIED LIFE SCIENCES
3-D tissue culture
B. anthracis Sterne
biothreats
computational model