Characterization of novel recombinant mycobacteriophages derived from homologous recombination between two temperate

Hamidu T Mohammed1,2, Catherine Mageeney1,3, Jamie Korenberg1,4

  • 1Department of Biological Sciences, Lehigh University, Bethlehem, PA 18015, USA.

G3 (Bethesda, Md.)
|September 15, 2023
PubMed

Insights

Mycobacteriophage Butters phages can recombine with Island3 phages, creating novel Butters-Island3-Butters (BIB) phages. These BIB phages overcome existing phage defenses, offering potential for new phage therapies.

Area of Science:

  • Bacteriophage biology
  • Genomics
  • Molecular evolution

Background:

  • Mycobacteriophage genomes exhibit significant genetic diversity and mosaicism.
  • The prophage of mycobacteriophage Butters (cluster N) confers resistance to infection by Island3 phages (subcluster I1).

Purpose of the Study:

  • To investigate the anti-Island3 defense mechanism of mycobacteriophage Butters.
  • To characterize the genetic basis of phage recombination and its implications for overcoming host defenses.

Main Methods:

  • Attempted isolation of Island3 defense escape mutants on a Butters lysogen.
  • Genomic analysis of resulting recombinant phages using techniques like transmission electron microscopy.
  • Identification of homologous recombination regions within the phage genomes.

Main Results:

  • Recombination between Butters and Island3 phages yielded novel Butters-Island3-Butters (BIB) mosaic phages.
  • Recombination occurred in specific homologous regions containing lysin, holin, RecE, and RecT genes.
  • BIB phages possess structural genes from Butters and an immunity cassette from Island3, rendering them homoimmune with Island3.
  • These recombinant phages successfully circumvented the antiphage defenses of the Butters lysogen.

Conclusions:

  • Phage recombination can generate novel genotypes that overcome existing antiphage defense systems.
  • The observed Butters-Island3 recombination provides a model for generating phages with altered host ranges and immunity profiles.
  • This recombination strategy offers a potential method for developing novel mycobacteriophages for therapeutic applications.

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