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

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

doi:10.1371/journal.pone.0219160

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

Journal Article · Mon Jul 01 00:00:00 EDT 2019 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0219160· OSTI ID:1557676

^[1]; Thomas, Dennis G. ^[1]; Weber, Thomas J. ^[1]; Hutchison, Janine R. ^[1]; Straub, Timothy M. ^[1]; Bruckner-Lea, Cynthia J. ^[1]; Powell, Joshua D. ^[2]; Kabilan, Senthil ^[3]; Corley, Richard A. ^[4]; Omri, Abdelwahab ^[5]

Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States); USDA-ARS National Animal Disease Center, Ames, IA (United States)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States); EMD Serono, Billerica, MA (United States)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Greek Creek Toxicokinetics Consulting, LLC, Boise, ID (United States)
Laurentian (Canada)

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.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1557676

Alternate ID(s):: OSTI ID: 1576229

Report Number(s):: PNNL-SA--140673

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 7 Vol. 14; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

References (15)

Construction of an in vitro primary lung co-culture platform derived from New Zealand white rabbits Powell, Joshua D.; Hess, Becky M.; Hutchison, Janine R. In Vitro Cellular & Developmental Biology - Animal, Vol. 51, Issue 5 https://doi.org/10.1007/s11626-014-9853-z	journal	December 2014
Modelling the variability of lag times and the first generation times of single cells of Metris, A.; Lemarc, Y.; Elfwing, A. International Journal of Food Microbiology, Vol. 100, Issue 1-3 https://doi.org/10.1016/j.ijfoodmicro.2004.10.004	journal	April 2005
Bacillus anthracis physiology and genetics Koehler, Theresa M. Molecular Aspects of Medicine, Vol. 30, Issue 6 https://doi.org/10.1016/j.mam.2009.07.004	journal	December 2009
Molecular pathogenesis of Bacillus anthracis infection Little, Stephen F.; Ivins, Bruce E. Microbes and Infection, Vol. 1, Issue 2 https://doi.org/10.1016/s1286-4579(99)80004-5	journal	February 1999
Biological Warfare and Bioterrorism: A Historical Review Riedel, Stefan Baylor University Medical Center Proceedings, Vol. 17, Issue 4 https://doi.org/10.1080/08998280.2004.11928002	journal	October 2004
Deterministic Models of Inhalational Anthrax in New Zealand White Rabbits Gutting, Bradford Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science, Vol. 12, Issue 1 https://doi.org/10.1089/bsp.2013.0067	journal	February 2014
Development of a Zealand white rabbit deposition model to study inhalation anthrax Asgharian, Bahman; Price, Owen; Kabilan, Senthil Inhalation Toxicology, Vol. 28, Issue 2 https://doi.org/10.3109/08958378.2016.1140850	journal	January 2016
A dynamic approach to predicting bacterial growth in food Baranyi, József; Roberts, Terry A. International Journal of Food Microbiology, Vol. 23, Issue 3-4 https://doi.org/10.1016/0168-1605(94)90157-0	journal	November 1994
Molecular pathogenesis of Bacillus anthracis infection Little, Stephen F.; Ivins, Bruce E. Microbes and Infection, Vol. 1, Issue 2 https://doi.org/10.1016/S1286-4579(99)80004-5	journal	February 1999
Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways Kabilan, S.; Suffield, S. R.; Recknagle, K. P. Journal of Aerosol Science, Vol. 99 https://doi.org/10.1016/j.jaerosci.2016.01.011	journal	September 2016
Inhalation Anthrax: Dose Response and Risk Analysis Coleman, Margaret E.; Thran, Brandolyn; Morse, Stephen S. Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science, Vol. 6, Issue 2 https://doi.org/10.1089/bsp.2007.0066	journal	June 2008
Alveolar epithelium protects macrophages from quorum sensing-induced cytotoxicity in a three-dimensional co-culture model: Quorum sensing effects in an alveolar tissue model Crabbé, Aurélie; Sarker, Shameema F.; Van Houdt, Rob Cellular Microbiology, Vol. 13, Issue 3 https://doi.org/10.1111/j.1462-5822.2010.01548.x	journal	November 2010
Bacillus anthracis spores germinate extracellularly at air-liquid interface in an in vitro lung model under serum-free conditions Powell, J. D.; Hutchison, J. R.; Hess, B. M. Journal of Applied Microbiology, Vol. 119, Issue 3 https://doi.org/10.1111/jam.12872	journal	July 2015
Dose-Response Modeling for Inhalational Anthrax in Rabbits Following Single or Multiple Exposures: Dose-Response Modeling for Inhalational Anthrax Gutting, Bradford W.; Rukhin, Andrey; Marchette, David Risk Analysis, Vol. 36, Issue 11 https://doi.org/10.1111/risa.12564	journal	February 2016
Behavior of Bacillus anthracis Strains Sterne and Ames K0610 in Sterile Raw Ground Beef Tamplin, M. L.; Phillips, R.; Stewart, T. A. Applied and Environmental Microbiology, Vol. 74, Issue 4 https://doi.org/10.1128/AEM.01292-07	journal	December 2007

Cited By (1)

Ventilation Modulation and Nanoparticle Deposition in Respiratory and Olfactory Regions of Rabbit Nose Xi, Jinxiang; Talaat, Mohamed; Si, Xiuhua Animals, Vol. 9, Issue 12 https://doi.org/10.3390/ani9121107	journal	December 2019

Similar Records

Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

Journal Article · Thu Sep 01 00:00:00 EDT 2016 · Journal of Aerosol Science · OSTI ID:1337237

Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

Journal Article · Fri Sep 30 00:00:00 EDT 2016 · Journal of Aerosol Science · OSTI ID:1330297

Related Subjects

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

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

Citation Formats

References (15)

Cited By (1)

Similar Records

Related Subjects