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Modelling of filamentous phage-induced antibiotic tolerance of P. aeruginosa
Maria van Rossem1, Sandra Wilks2, Malgosia Kaczmarek1
1Physics and Astronomy, University of Southampton, Southampton, Hampshire, United Kingdom.
Abstract:
Filamentous molecules tend to spontaneously assemble into liquid crystalline droplets with a tactoid morphology in environments with high concentration on non-adsorbing molecules. Tactoids of filamentous Pf bacteriophage, such as those produced by Pseudomonas aeruginosa, have been linked to increased antibiotic tolerance. We modelled this system and show that tactoids composed of filamentous Pf virions can lead to antibiotic tolerance by acting as an adsorptive diffusion barrier. The continuum model, reminiscent of descriptions of reactive diffusion in porous media, has been solved numerically and good agreement was found with the analytical results, obtained using a homogenisation approach. We find that the formation of tactoids significantly increases antibiotic diffusion times which may lead to stronger antibiotic resistance.
Insights
Filamentous bacteriophage tactoids, structures formed by Pseudomonas aeruginosa, can increase antibiotic resistance. These tactoids act as barriers, slowing antibiotic diffusion and enhancing bacterial tolerance.
Area of Science:
- Microbiology
- Biophysics
- Mathematical Modeling
Background:
- Filamentous molecules self-assemble into liquid crystalline tactoids at high concentrations.
- Tactoids of filamentous Pf bacteriophage (Pseudomonas aeruginosa) are associated with increased antibiotic tolerance.
Purpose of the Study:
- To model the interaction of filamentous bacteriophage tactoids with antibiotics.
- To investigate the mechanism by which tactoids contribute to antibiotic tolerance.
Main Methods:
- Developed a continuum model for reactive diffusion within tactoids.
- Solved the model numerically and validated with analytical homogenization methods.
Main Results:
- Tactoids act as adsorptive diffusion barriers for antibiotics.
- The formation of tactoids significantly increases antibiotic diffusion times.
- Increased diffusion times correlate with enhanced antibiotic resistance.
Conclusions:
- Filamentous bacteriophage tactoids can promote antibiotic tolerance in bacterial populations.
- The physical barrier created by tactoids is a key factor in this phenomenon.
- Mathematical modeling provides insights into antimicrobial resistance mechanisms.
