A mycobacteriophage is a member of a group of bacteriophages known to have mycobacteria as host bacterial species. While originally isolated from the bacterial species Mycobacterium smegmatis and Mycobacterium tuberculosis, the causative agent of tuberculosis, more than 4,200 mycobacteriophage have since been isolated from various environmental and clinical sources. Almost 600 have been completely sequenced. Mycobacteriophages have served as examples of viral lysogeny and of the divergent morphology and genetic arrangement characteristic of many phage types.
A bacteriophage was found to infect Mycobacterium smegmatis in 1947 and was the first documented example of a mycobacteriophage. It was found in cultures of the bacteria originally growing in moist compost. The first bacteriophage that infects M. tuberculosis was discovered in 1954.
The first sequenced mycobacteriophage genome was that of mycobacteriophage L5 in 1993. In the following years hundreds of additional genomes have been sequenced. Mycobacteriophages have highly mosaic genomes. Their genome sequences show evidence of extensive horizontal genetic transfer, both between phages and between phages and their mycobacterial hosts. Comparisons of these sequences have helped to explain how frequently genetic exchanges of this type may occur in nature, as well as how phages may contribute to bacterial pathogenicity.
A selection of 60 mycobacteriophages were isolated and had their genomes sequenced in 2009. These genome sequences were grouped into clusters by several methods in an effort to determine similarities between the phages and to explore their genetic diversity. More than half of the phage species were originally found in or near Pittsburgh, Pennsylvania, though others were found in other United States locations, India, and Japan. No distinct differences were found in the genomes of mycobacteriophage species from different global origins.
Mycobacteriophage genomes have been found to contain a subset of genes undergoing more rapid genetic flux than other elements of the genomes. These "rapid flux" genes are exchanged between mycobacteriophage more often and are 50 percent shorter in sequence than the average mycobacteriophage gene.
Historically, mycobacteriophage have been used to "type" (i.e. "diagnose") mycobacteria, as each phage infects only one or a few bacterial strains. In the 1980s phages were discovered as tools to genetically manipulate their hosts. For instance, phage TM4 was used to construct shuttle phasmids that replicate as large cosmids in Escherichia coli and as phages in mycobacteria. Shuttle phasmids can be manipulated in E. coli us and used to efficiently introduce foreign DNA into mycobacteria.
Phages with mycobacterial hosts may be especially useful for understanding and fighting mycobacterial infections in humans. A system has been developed to use mycobacteriophage carrying a reporter gene to screen strains of M. tuberculosis for antibiotic resistance. In the future, mycobacteriophage could be used to treat infections by phage therapy.
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