%0 Journal Article %T Cluster K Mycobacteriophages: Insights into the Evolutionary Origins of Mycobacteriophage TM4 %A Welkin H. Pope %A Christina M. Ferreira %A Deborah Jacobs-Sera %A Robert C. Benjamin %A Ariangela J. Davis %A Randall J. DeJong %A Sarah C. R. Elgin %A Forrest R. Guilfoile %A Mark H. Forsyth %A Alexander D. Harris %A Samuel E. Harvey %A Lee E. Hughes %A Peter M. Hynes %A Arrykka S. Jackson %A Marilyn D. Jalal %A Elizabeth A. MacMurray %A Coreen M. Manley %A Molly J. McDonough %A Jordan L. Mosier %A Larissa J. Osterbann %A Hannah S. Rabinowitz %A Corwin N. Rhyan %A Daniel A. Russell %A Margaret S. Saha %A Christopher D. Shaffer %A Stephanie E. Simon %A Erika F. Sims %A Isabel G. Tovar %A Emilie G. Weisser %A John T. Wertz %A Kathleen A. Weston-Hafer %A Kurt E. Williamson %A Bo Zhang %A Steven G. Cresawn %A Paras Jain %A Mariana Piuri %A William R. Jacobs %A Roger W. Hendrix %A Graham F. Hatfull %J PLOS ONE %D 2011 %I Public Library of Science (PLoS) %R 10.1371/journal.pone.0026750 %X Five newly isolated mycobacteriophages ¨CAngelica, CrimD, Adephagia, Anaya, and Pixie ¨C 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 ¨C with the exception of TM4 ¨C 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. %U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0026750