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

Autor: Hess BM; Chemical and Biological Signature Sciences, Pacific Northwest National Laboratory, Richland, WA, United States of America., Thomas DG; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, United States of America., Weber TJ; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, United States of America., Hutchison JR; Chemical and Biological Signature Sciences, Pacific Northwest National Laboratory, Richland, WA, United States of America., Straub TM; Chemical and Biological Signature Sciences, Pacific Northwest National Laboratory, Richland, WA, United States of America., Bruckner-Lea CJ; Chemical and Biological Signature Sciences, Pacific Northwest National Laboratory, Richland, WA, United States of America., Powell JD; Chemical and Biological Signature Sciences, Pacific Northwest National Laboratory, Richland, WA, United States of America., Kabilan S; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, United States of America., Corley RA; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2019 Jul 01; Vol. 14 (7), pp. e0219160. Date of Electronic Publication: 2019 Jul 01 (Print Publication: 2019).
DOI: 10.1371/journal.pone.0219160
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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