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Modeling Polygenic Antibiotic Resistance Evolution in Biofilms.

Barbora Trubenová1, Dan Roizman2, Jens Rolff2

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Biofilm recalcitrance to antimicrobials involves multiple factors, with increased genetic diversity enhancing survival. A new polygenic model predicts resistance evolution timing and consequences under various conditions.

Keywords:
PK/PDantibiotic resistancebiofilm recalcitrancemathematical modelingpopulation geneticsresistance evolution

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Area of Science:

  • Microbiology
  • Evolutionary Biology
  • Pharmacology

Background:

  • Biofilm recalcitrance to antimicrobials is a complex issue.
  • Multiple factors including genetic, physical, and physiological changes contribute to this phenomenon.
  • Increased biofilm genetic diversity is an emerging factor enhancing recalcitrance.

Purpose of the Study:

  • To develop a polygenic model of biofilm recalcitrance.
  • To account for multiple phenotypic mechanisms contributing to biofilm recalcitrance.
  • To predict the emergence, timing, and population genetic consequences of antimicrobial resistance in biofilms.

Main Methods:

  • Development of a polygenic model for biofilm recalcitrance.
  • Simulation of various treatment and experimental setups using the model.
  • Comparison of model predictions with published experimental observations.

Main Results:

  • The model predicts that antimicrobial resistance evolution is impaired at low antimicrobial concentrations but facilitated at higher concentrations in biofilms.
  • Bacteria exchange between planktonic and biofilm compartments further facilitates resistance evolution.
  • The relative contributions of different recalcitrance factors depend on antibiotics, bacterial strain, and environmental conditions.

Conclusions:

  • A polygenic model can effectively predict antimicrobial resistance evolution in biofilms.
  • Antimicrobial concentration and bacteria exchange dynamics significantly influence resistance development.
  • Understanding these factors is crucial for developing effective antimicrobial strategies against biofilms.