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Pope WH, Ferreira CM, Jacobs-Sera D, et al. Cluster K mycobacteriophages: insights into the evolutionary origins of mycobacteriophage TM4. PLoS One. 2011;6(10):e26750. doi:10.1371/journal.pone.0026750
Five newly isolated mycobacteriophages--Angelica, CrimD, Adephagia, Anaya, and Pixie--have similar genomic architectures to mycobacteriophage TM4, a previously characterized phage that is widely used in mycobacterial genetics. The nucleotide sequence similarities warrant grouping these into Cluster K, with subdivision into three subclusters: K1, K2, and K3. Although the overall genome architectures of these phages are similar, TM4 appears to have lost at least two segments of its genome, a central region containing the integration apparatus, and a segment at the right end. This suggests that TM4 is a recent derivative of a temperate parent, resolving a long-standing conundrum about its biology, in that it was reportedly recovered from a lysogenic strain of Mycobacterium avium, but it is not capable of forming lysogens in any mycobacterial host. Like TM4, all of the Cluster K phages infect both fast- and slow-growing mycobacteria, and all of them--with the exception of TM4--form stable lysogens in both Mycobacterium smegmatis and Mycobacterium tuberculosis; immunity assays show that all five of these phages share the same immune specificity. TM4 infects these lysogens suggesting that it was either derived from a heteroimmune temperate parent or that it has acquired a virulent phenotype. We have also characterized a widely-used conditionally replicating derivative of TM4 and identified mutations conferring the temperature-sensitive phenotype. All of the Cluster K phages contain a series of well conserved 13 bp repeats associated with the translation initiation sites of a subset of the genes; approximately one half of these contain an additional sequence feature composed of imperfectly conserved 17 bp inverted repeats separated by a variable spacer. The K1 phages integrate into the host tmRNA and the Cluster K phages represent potential new tools for the genetics of M. tuberculosis and related species.
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Pope, Welkin; Ferreira, Christina; Jacobs-Sera, Deborah; Benjamin, Robert; Davis, Ariangela; Dejong, Randall; Elgin, Sarah C.R.; Guilfoile, Forrest; Forsyth, Mark; Harris, Alexander; Harvey, Samuel; Hughes, Lee; Hynes, Peter; Jackson, Arrykka; Jalal, Marilyn; MacMurray, Elizabeth; Manley, Coreen; McDonough, Molly; Mosier, Jordan; Osterbann, Larissa; Rabinowitz, Hannah; Rhyan, Corwin; Russell, Daniel; Saha, Margaret; Shaffer, Christopher; Simon, Stephanie; Sims, Erika; Tovar, Isabel; Weisser, Emilie; Wertz, John; Weston-Hafer, Kathleen; Williamson, Kurt; Zhang, Bo; Cresawn, Steven; Jain, Paras; Piuri, Mariana; Jacobs, William; Hendrix, Roger; and Hatfull, Graham, "Cluster K mycobacteriophages: insights into the evolutionary origins of mycobacteriophage TM4" (2011). Biology Faculty Publications & Presentations. 186.