Model of bacterial toxin-dependent pathogenesis explains infective dose Journal Article


Author(s): Rybicki, Joel; Kisdi, Eva; Anttila, Jani V
Article Title: Model of bacterial toxin-dependent pathogenesis explains infective dose
Affiliation IST Austria
Abstract: The initial amount of pathogens required to start an infection within a susceptible host is called the infective dose and is known to vary to a large extent between different pathogen species. We investigate the hypothesis that the differences in infective doses are explained by the mode of action in the underlying mechanism of pathogenesis: Pathogens with locally acting mechanisms tend to have smaller infective doses than pathogens with distantly acting mechanisms. While empirical evidence tends to support the hypothesis, a formal theoretical explanation has been lacking. We give simple analytical models to gain insight into this phenomenon and also investigate a stochastic, spatially explicit, mechanistic within-host model for toxin-dependent bacterial infections. The model shows that pathogens secreting locally acting toxins have smaller infective doses than pathogens secreting diffusive toxins, as hypothesized. While local pathogenetic mechanisms require smaller infective doses, pathogens with distantly acting toxins tend to spread faster and may cause more damage to the host. The proposed model can serve as a basis for the spatially explicit analysis of various virulence factors also in the context of other problems in infection dynamics.
Keywords: Pathogen; parasite; Infective dose; Pathogenesis; Spatial model
Journal Title: AIP: Conference Proceedings
Volume: 115
Issue 42
ISSN: 00278424
Publisher: National Academy of Sciences  
Date Published: 2018-10-02
Start Page: 10690
End Page: 10695
DOI: 10.1073/pnas.1721061115
Notes: This project received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant 754411 (to J.R.) and from the Academy of Finland through the Center of Excellence in Analysis and Dynamics Research (E.K.). J.R. and J.V.A. were also supported by the Academy of Finland Grants 1273253 and 267541.
Open access: no