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How does feedback from phage infections influence the evolution of phase variation in Campylobacter?
Simran K Sandhu1, Christopher D Bayliss2, Andrew Yu Morozov1,3
1Department of Mathematics, University of Leicester, Leicester, United Kingdom.
Plos Computational Biology
|June 14, 2021
Summary
Bacterial phase variation (PV) helps Campylobacter jejuni resist phage therapy. Computational models show that counter-selection pressure is key for maintaining phage effectiveness against evolving bacterial resistance mechanisms.
Area of Science:
- Microbiology
- Evolutionary Biology
- Computational Biology
Background:
- Campylobacter jejuni (C. jejuni) causes significant global health and economic burdens due to foodborne illness.
- Phage therapy offers a promising strategy for controlling C. jejuni in poultry.
- Bacterial resistance to phages can evolve via phase-variable (PV) ON/OFF switching of phage receptors, often mediated by simple sequence repeats (SSR).
Purpose of the Study:
- To computationally model the evolution of PV rates in C. jejuni under different selective pressures.
- To investigate how bacterial-phage dynamics are influenced by SSR-mediated PV.
- To explore conditions favoring the success or failure of phage therapy against C. jejuni.
Main Methods:
- Development of continuous culture bacteria-phage computational models.
- Simulation of PV rate evolution using the adaptive dynamics framework.
- Calibration of models with experimental SSR rates for C. jejuni and replication parameters for the F336 phage.
Main Results:
- Growth-reducing counter-selection on a single PV locus stabilized phage presence.
- Compensatory selection between bacterial states led to disadvantageous high or low mutation rates.
- In the absence of selection, PV rates evolved below basal levels.
- A two-locus PV model resulted in phage extinction, suggesting a need for additional counter-selection.
Conclusions:
- A balance between counter-selection and phage attack is crucial for the evolution of PV phage receptors and the persistence of PV-receptor-specific phages.
- Phage therapy efficacy against C. jejuni may depend on managing bacterial resistance evolution through specific selective pressures.
- Further research into multi-locus PV and combination therapies is warranted for effective C. jejuni control.
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