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Phage-Mediated Genetic Manipulation of the Lyme Disease Spirochete Borrelia burgdorferi

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Controlling Recombination to Evolve Bacteriophages.

James J Bull^1,2, Holly A Wichman^1,2, Stephen M Krone^2,3

¹Department of Biological Sciences, University of Idaho, Moscow, ID 83844, USA.

|April 12, 2024

Summary

This summary is machine-generated.

Directing phage host range evolution for phage therapy requires enabling recombination. High infection force and multiplicity of infection (MOI) promote coinfection, a key step for recombination, though fine-tuning wild phage recombination is challenging.

Keywords:

computational model mathematical model phage therapy protocol

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Area of Science:

Microbiology
Evolutionary Biology
Computational Biology

Background:

Bacteriophage recombination can enhance host range expansion.
Phage therapy applications may benefit from protocols that promote phage recombination.
Understanding recombination mechanisms is crucial for engineering phages.

Purpose of the Study:

To investigate how experimental protocols influence phage recombination rates.
To identify conditions that maximize coinfection, a prerequisite for recombination.
To model the accumulation of recombinants under different growth conditions.

Main Methods:

Mathematical and computational modeling.
Experimental evolution using bacteriophages T3 and T7.
Analysis of coinfection dynamics based on multiplicity of infection (MOI) and force of infection.
A four-genetic-locus model to assess recombinant levels.

Main Results:

High multiplicity of infection (MOI > 1) and high force of infection are critical for achieving high coinfection levels.
Recombinant phages accumulate over generations, but this can be reduced if one phage lineage dominates.
Supplementing with low-fitness phages can partially restore lost recombination.
Fine-tuning recombination in wild phages is difficult, but qualitative enhancement is possible.

Conclusions:

Coinfection levels are influenced by both MOI and force of infection, not just MOI alone.
Protocols can be designed to qualitatively enhance phage recombination for applications like phage therapy.
While precise control is elusive, basic procedures can promote beneficial phage evolution.