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

Journal Article · · G3
 [1];  [2];  [3];  [4];  [4]
  1. Lehigh University, Bethlehem, PA (United States); Memsel, Inc., Fort Worth, TX (United States)
  2. Lehigh University, Bethlehem, PA (United States); Sandia National Laboratories (SNL-CA), Livermore, CA (United States)
  3. Lehigh University, Bethlehem, PA (United States); New York Institute of Technology College of Osteopathic Medicine, Glen Head, NY (United States)
  4. Lehigh University, Bethlehem, PA (United States)

Comparative analyses of mycobacteriophage genomes reveals extensive genetic diversity in genome organization and gene content, contributing to widespread mosaicism. We previously reported that the prophage of mycobacteriophage Butters (cluster N) provides defense against infection by Island3 (subcluster I1). To explore the anti-Island3 defense mechanism, we attempted to isolate Island3 defense escape mutants on a Butters lysogen, but only uncovered phages with recombinant genomes comprised of regions of Butters and Island3 arranged from left arm to right arm as Butters-Island3-Butters (BIBs). Recombination occurs within two distinct homologous regions that encompass lysin A, lysin B, and holin genes in one segment, and RecE and RecT genes in the other. Structural genes of mosaic BIB genomes are contributed by Butters while the immunity cassette is derived from Island3. Consequently, BIBs are morphologically identical to Butters (as shown by transmission electron microscopy) but are homoimmune with Island3. Recombinant phages overcome antiphage defense and silencing of the lytic cycle. We leverage this observation to propose a stratagem to generate novel phages for potential therapeutic use.

Research Organization:
Sandia National Laboratories (SNL-CA), Livermore, CA (United States)
Sponsoring Organization:
USDOE National Nuclear Security Administration (NNSA); Pennsylvania Department of Community and Economic Development (PITA)
Grant/Contract Number:
NA0003525
OSTI ID:
2471744
Journal Information:
G3, Journal Name: G3 Journal Issue: 12 Vol. 13; ISSN 2160-1836
Publisher:
Genetics Society of AmericaCopyright Statement
Country of Publication:
United States
Language:
English

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