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G3 (Bethesda). 2021 Oct 19;11(11). doi: 10.1093/g3journal/jkab291.

Phylogenetic relationships and codon usage bias amongst cluster K mycobacteriophages.

G3 (Bethesda, Md.)

Adele Crane, Cyril J Versoza, Tiana Hua, Rohan Kapoor, Lillian Lloyd, Rithik Mehta, Jueliet Menolascino, Abraham Morais, Saige Munig, Zeel Patel, Daniel Sackett, Brandon Schmit, Makena Sy, Susanne P Pfeifer

Affiliations

  1. School of Life Sciences, Arizona State University, Tempe, AZ 85281, USA.
  2. Center for Evolution and Medicine, Arizona State University, Tempe, AZ 85281, USA.
  3. Center for Mechanisms of Evolution, Arizona State University, Tempe, AZ 85281, USA.

PMID: 34849792 PMCID: PMC8527509 DOI: 10.1093/g3journal/jkab291

Abstract

Bacteriophages infecting pathogenic hosts play an important role in medical research, not only as potential treatments for antibiotic-resistant infections but also offering novel insights into pathogen genetics and evolution. A prominent example is cluster K mycobacteriophages infecting Mycobacterium tuberculosis, a causative agent of tuberculosis in humans. However, as handling M. tuberculosis as well as other pathogens in a laboratory remains challenging, alternative nonpathogenic relatives, such as Mycobacterium smegmatis, are frequently used as surrogates to discover therapeutically relevant bacteriophages in a safer environment. Consequently, the individual host ranges of the majority of cluster K mycobacteriophages identified to date remain poorly understood. Here, we characterized the complete genome of Stinson, a temperate subcluster K1 mycobacteriophage with a siphoviral morphology. A series of comparative genomic analyses revealed strong similarities with other cluster K mycobacteriophages, including the conservation of an immunity repressor gene and a toxin/antitoxin gene pair. Patterns of codon usage bias across the cluster offered important insights into putative host ranges in nature, highlighting that although all cluster K mycobacteriophages are able to infect M. tuberculosis, they are less likely to have shared an evolutionary infection history with Mycobacterium leprae (underlying leprosy) compared to the rest of the genus' host species. Moreover, subcluster K1 mycobacteriophages are able to integrate into the genomes of Mycobacterium abscessus and Mycobacterium marinum-two bacteria causing pulmonary and cutaneous infections which are often difficult to treat due to their drug resistance.

© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.

Keywords: de novo assembly; cluster K; codon usage bias; genome annotation; mycobacteriophages; phylogeny

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