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Quantifying the Cytotoxicity of Staphylococcus aureus Against Human Polymorphonuclear Leukocytes
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A dose response model for Staphylococcus aureus.

Srikiran Chandrasekaran1, Sunny C Jiang2

  • 1Civil and Environmental Engineering, University of California, Irvine, Irvine, 92697, USA. srikiranc@gmail.com.

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|June 16, 2021
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Summary
This summary is machine-generated.

We developed a new two-compartment model for Staphylococcus aureus (SA) infections. This model shows bacterial cooperation is key to predicting infection risk, advancing dose-response modeling.

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Area of Science:

  • Microbiology
  • Infectious Disease Modeling
  • Quantitative Microbial Risk Assessment

Background:

  • Dose-response models (DRMs) predict infection probability from pathogen exposure.
  • Current Staphylococcus aureus (SA) DRMs are limited, assuming no bacterial interaction.
  • SA causes significant skin and soft-tissue infections.

Purpose of the Study:

  • To propose a novel, mechanistic two-compartment (2C) dose-response model for SA.
  • To explicitly model the stochastic transition of bacteria between un-adjusted and adjusted host states.
  • To demonstrate the necessity of bacterial cooperation in SA pathogenesis.

Main Methods:

  • Developed a two-compartment (2C) model incorporating bacterial decay and logistic/cooperative growth.
  • Modeled the stochastic transition between bacterial states within the host.
  • Fitted the 2C model to SA pathogenesis data.

Main Results:

  • Bacterial cooperation is sufficient and necessary to characterize SA dose-response within the 2C model.
  • The 2C model departs from classical single-hit theory by not assuming pathogen independence.
  • The model successfully predicts response probabilities based on pathogen exposure.

Conclusions:

  • The proposed 2C DRM provides a more mechanistic understanding of SA infections.
  • This model enables transparent dose-response assessment for antibiotic-resistant SA.
  • It facilitates modeling of complex exposure scenarios with fewer assumptions.