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Mycobacteriophage

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20: 253:, 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. 146: 221:(Figure 1). However, mutants can be readily isolated from some phages that expand their host range to infect these other strains. However, the molecular basis of host range depends on the behavior and presence of specific genes.  This raises the probability of a correlation between gene phamilies and the preferred host. 248:
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
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The realms of mycobacteriophage infection are not understood in its entirety because it involves various mechanisms including receptor availability, restriction-modification, abortive infection, and more. These mechanisms can be mediated through several processes like Clustered Regulatory Interspaced
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became negative after approximately 100 days of combined phage and antibiotic treatment, and a variety of biomarkers confirmed the therapeutic response. The individual received a bilateral lung transplant after 379 days of treatment, and cultures from the explanted lung tissue confirmed eradication
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profiles does not appear to be detrimental. Because new mycobacteriophages lacking extensive DNA similarity with the extant collection are still being discovered, and as there are at least seven singletons for which no relatives have been isolated, we clearly have yet to saturate the diversity of
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Figure 1. Diversity of mycobacteriophages. Sequenced genomes for 471 mycobacteriophages were compared according to their shared gene contents and overall nucleotide sequence similarity. Colored circles encompass Clusters A–T as indicated, and grey circles represent singleton genomes that have no
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infection that occurred following lung transplant. The patient had clear benefit from treatment, and the phage treatment combined with antibiotics was extended for several years. In 2022 it was reported that two mycobacteriophages were administered intravenously twice daily to a young man with
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patients, although these have yet to be sequenced. About 30 distinct types (called clusters, or singletons if they have no relatives) that share little nucleotide sequence similarity have been identified. Many of the clusters span sufficient diversity that the genomes warrant division into
138:, i.e. phage protein families) according to their shared amino acid sequences. Most of these phamilies (~75%) do not have homologues outside of the mycobacteriophages and are of unknown function. Genetic studies with mycobacteriophage Giles show that 45% of the genes are nonessential for 261:
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
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close relatives. A1, A2, A3... indicate subclusters. Micrographs show the morphotypes of the myoviral Cluster C phages and the siphoviruses (all others) that primarily differ in tail length (scale bars: 100 nm). With the exception of DS6A (a singleton), all phages infect
241:, 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 884:
Jacobs-Sera D, Marinelli LJ, Bowman C, Broussard GW, Guerrero Bustamante C, Boyle MM, et al. (Science Education Alliance Phage Hunters Advancing Genomics And Evolutionary Science Sea-Phages Program) (December 2012).
55:, more than 4,200 mycobacteriophage have since been isolated from various environmental and clinical sources. 2,042 have been completely sequenced. Mycobacteriophages have served as examples of viral 162:
As of May 2023, the PhagesDB website lists 12579 reported mycobacteriophages, 2257 of which having been sequenced. Around one-third of the sequenced phages fall into cluster "A", which contains L5.
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Jacobs WR Jr. 2000. Mycobacterium tuberculosis: a once genetically intractable organism. In Molecular Genetics of the Mycobacteria, ed. GF Hatfull, WR Jacobs Jr, pp. 1–16. Washington, DC: ASM Press
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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
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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
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mc2155, over 1400 of which have been completely sequenced. These are mostly from environmental samples, but mycobacteriophages have also been isolated from stool samples of
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Short Palindromic Repeats (CRISPRs) and the translational apparatus being modified. Phages overcome these constraints by evolving, spontaneous mutation, and diversifying.
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Danelishvili L, Young LS, Bermudez LE (2006). "In vivo efficacy of phage therapy for Mycobacterium avium infection as delivered by a nonvirulent mycobacterium".
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Hatfull GF, Sarkis GJ (February 1993). "DNA sequence, structure and gene expression of mycobacteriophage L5: a phage system for mycobacterial genetics".
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In line with the clustering results by phageDB, mycobacteriophages are split into many places on the ICTV's virus taxonomy tree. Some examples are:
1167:"Generation of a novel nucleic acid-based reporter system to detect phenotypic susceptibility to antibiotics in Mycobacterium tuberculosis" 86:
in 1947 was the first documented example of a mycobacteriophage. It was found in cultures of the bacteria originally growing in moist
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In 2019 it was reported that three mycobacteriophages were administered intravenously twice daily to a 15 year-old girl with
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Mankiewicz E (September 1961). "Mycobacteriophages isolated from persons with tuberculous and non-tuberculous conditions".
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Cater JC, Redmond WB (May 1963). "Mycobacterial phages isolated from stool specimens of patients with pulmonary disease".
1418: 47: 1031:"Comparative genomic analysis of 60 Mycobacteriophage genomes: genome clustering, gene acquisition, and gene size" 1294:"Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus" 304: 1114:
Jacobs WR, Tuckman M, Bloom BR (1987). "Introduction of foreign DNA into mycobacteria using a shuttle phasmid".
751:"Functional requirements for bacteriophage growth: gene essentiality and expression in mycobacteriophage Giles" 250: 238: 217:
infect other strains and only phages in Cluster K and in certain subclusters of Cluster A efficiently infect
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is 67.3%). Thus, phage GC% does not necessarily match that of its host, and the consequent mismatch of
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Dedrick RM, Guerrero-Bustamante CA, Garlena RA, Russell DA, Ford K, Harris K, et al. (May 2019).
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Pope WH, Jacobs-Sera D, Russell DA, Peebles CL, Al-Atrache Z, Alcoser TA, et al. (January 2011).
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for antibiotic resistance. In the future, mycobacteriophage could be used to treat infections by
493:"Expanding the diversity of mycobacteriophages: insights into genome architecture and evolution" 977:
Pedulla ML, Ford ME, Houtz JM, Karthikeyan T, Wadsworth C, Lewis JA, et al. (April 2003).
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Hatfull GF, Jacobs-Sera D, Lawrence JG, Pope WH, Russell DA, Ko CC, et al. (March 2010).
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and of the divergent morphology and genetic arrangement characteristic of many phage types.
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McNerney R, TraorΓ© H (2005). "Mycobacteriophage and their application to disease control".
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Nick JA, Dedrick RM, Gray AL, Vladar EK, Smith BE, Freeman KG, et al. (May 2022).
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Jones WD (1975). "Phage typing report of 125 strains of "Mycobacterium tuberculosis"".
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Gardner GM, Weiser RS (October 1947). "A bacteriophage for Mycobacterium smegmatis".
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Dedrick RM, Marinelli LJ, Newton GL, Pogliano K, Pogliano J, Hatfull GF (May 2013).
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as host bacterial species. While originally isolated from the bacterial species
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Thousands of mycobacteriophage have been isolated using a single host strain,
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genomes and have been classified by their structure and appearance into
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Hatfull GF (13 October 2010). "Mycobacteriophages: genes and genomes".
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and as phages in mycobacteria. Shuttle phasmids can be manipulated in
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mc2155. Cluster K phages and a subset of Cluster A phages also infect
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and used to efficiently introduce foreign DNA into mycobacteria.
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Proceedings of the Society for Experimental Biology and Medicine
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Host range analysis shows that not all mycobacteriophages from
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Mycobacteriophage ZoeJ Structural Model at Atomic Resolution
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genomes. Their genome sequences show evidence of extensive
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Mycobacteriophage ZoeJ Structural Model at Atomic Resolution
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American Journal of Public Health and the Nation's Health
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Annali Sclavo; Rivista di Microbiologia e di Immunologia
1401: 434: 979:"Origins of highly mosaic mycobacteriophage genomes" 1165:Mulvey MC, Sacksteder KA, Einck L, Nacy CA (2012). 118:(GC%), from 50.3% to 70%, with an average of 64% ( 676:: CS1 maint: DOI inactive as of September 2024 ( 700:"Mycobacteriophages: windows into tuberculosis" 134:can be sorted into >3,900 groups (so-called 62:All mycobacteriophages found thus far have had 1024: 1022: 879: 877: 875: 873: 693: 691: 689: 687: 174:Phage L5 and its relatives are classified as 8: 114:There is also considerable range in overall 824:"Taxonomy browser (Mycobacterium phage L5)" 593:Froman S, Will DW, Bogen E (October 1954). 644:The American Review of Respiratory Disease 429: 427: 425: 1366: 1317: 1190: 1054: 994: 910: 774: 725: 715: 618: 526: 516: 339: 90:. The first bacteriophage that infects 669: 321:  pulmonary infection and severe 7: 842:"Taxonomy browser (Timquatrovirus)" 470:10.1146/annurev.micro.112408.134233 948:10.1111/j.1365-2958.1993.tb01131.x 347:Padilla-Sanchez V (24 July 2021), 325:lung disease. Airway cultures for 14: 860:"Taxonomy browser (Corndogvirus)" 198:Phage "Corndog" is classified as 1263:10.1111/j.1365-2672.2005.02596.x 803:The Actinobacteriophage Database 82:A bacteriophage found to infect 1251:Journal of Applied Microbiology 799:"By host genera: Mycobacterium" 189:ZoeJ and TM4 are classified as 658:(inactive 12 September 2024). 116:guanine plus cytosine content 1: 996:10.1016/S0092-8674(03)00233-2 458:Annual Review of Microbiology 130:The collection of >50,000 1035:Journal of Molecular Biology 717:10.1371/journal.ppat.1003953 518:10.1371/journal.pone.0016329 435:"Mycobacteriophage Database" 249:originally found in or near 127:this particular population. 16:Virus infecting mycobacteria 903:10.1016/j.virol.2012.09.026 239:horizontal genetic transfer 1435: 1402:Mycobacteriophage Database 1359:10.1016/j.cell.2022.04.024 656:10.1164/arrd.1963.87.5.726 48:Mycobacterium tuberculosis 31:is a member of a group of 1310:10.1038/s41591-019-0437-z 1216:Microbial Drug Resistance 1047:10.1016/j.jmb.2010.01.011 698:Hatfull GF (March 2014). 564:10.3181/00379727-66-16037 51:, the causative agent of 266:that replicate as large 251:Pittsburgh, Pennsylvania 111:subclusters (Figure 1). 94:was discovered in 1954. 611:10.2105/AJPH.44.10.1326 104:Mycobacterium smegmatis 84:Mycobacterium smegmatis 42:Mycobacterium smegmatis 936:Molecular Microbiology 755:Molecular Microbiology 359:10.5281/zenodo.5132914 183:Mycobacterium virus L5 159: 24: 1353:(11): 1860–1874.e12. 1228:10.1089/mdr.2006.12.1 1183:10.1128/mBio.00312-11 313:treatment-refractory 287:to screen strains of 148: 22: 864:www.ncbi.nlm.nih.gov 846:www.ncbi.nlm.nih.gov 828:www.ncbi.nlm.nih.gov 1128:1987Natur.327..532J 509:2011PLoSO...616329P 392:1961Natur.191.1416M 386:(4796): 1416–1417. 229:Genome architecture 158:. From Hatfull 2014 64:double-stranded DNA 1419:Mycobacteriophages 195:(named after TM4). 160: 25: 1122:(6122): 532–535. 767:10.1111/mmi.12210 605:(10): 1326–1333. 400:10.1038/1911416b0 330:of the bacteria. 302:and disseminated 29:mycobacteriophage 1426: 1389: 1388: 1370: 1338: 1332: 1331: 1321: 1289: 1283: 1282: 1246: 1240: 1239: 1211: 1205: 1204: 1194: 1177:(2): e00312–11. 1162: 1156: 1155: 1136:10.1038/327532a0 1111: 1105: 1102: 1096: 1095: 1075: 1069: 1068: 1058: 1026: 1017: 1016: 998: 974: 968: 967: 931: 925: 924: 914: 881: 868: 867: 856: 850: 849: 838: 832: 831: 820: 814: 813: 811: 809: 795: 789: 788: 778: 746: 740: 739: 729: 719: 695: 682: 681: 675: 667: 639: 633: 632: 622: 590: 584: 583: 547: 541: 540: 530: 520: 488: 482: 481: 453: 447: 446: 444: 442: 431: 420: 419: 375: 369: 368: 367: 365: 344: 273:Escherichia coli 1434: 1433: 1429: 1428: 1427: 1425: 1424: 1423: 1409: 1408: 1398: 1393: 1392: 1340: 1339: 1335: 1298:Nature Medicine 1291: 1290: 1286: 1248: 1247: 1243: 1213: 1212: 1208: 1164: 1163: 1159: 1113: 1112: 1108: 1103: 1099: 1077: 1076: 1072: 1028: 1027: 1020: 976: 975: 971: 933: 932: 928: 883: 882: 871: 858: 857: 853: 840: 839: 835: 822: 821: 817: 807: 805: 797: 796: 792: 748: 747: 743: 710:(3): e1003953. 697: 696: 685: 668: 641: 640: 636: 592: 591: 587: 549: 548: 544: 490: 489: 485: 455: 454: 450: 440: 438: 433: 432: 423: 377: 376: 372: 363: 361: 346: 345: 341: 336: 323:cystic fibrosis 300:cystic fibrosis 289:M. tuberculosis 259: 231: 219:M. tuberculosis 211: 168: 156:M. tuberculosis 100: 92:M. tuberculosis 80: 17: 12: 11: 5: 1432: 1430: 1422: 1421: 1411: 1410: 1405: 1404: 1397: 1396:External links 1394: 1391: 1390: 1333: 1304:(5): 730–733. 1284: 1257:(2): 223–233. 1241: 1206: 1157: 1106: 1097: 1086:(4): 599–604. 1070: 1041:(1): 119–143. 1018: 989:(2): 171–182. 969: 942:(3): 395–405. 926: 897:(2): 187–201. 869: 851: 833: 815: 790: 761:(3): 577–589. 741: 704:PLOS Pathogens 683: 634: 585: 558:(1): 205–206. 542: 483: 464:(1): 331–356. 448: 437:. Phagesdb.org 421: 370: 338: 337: 335: 332: 258: 255: 230: 227: 210: 207: 206: 205: 196: 192:Timquatrovirus 187: 167: 164: 99: 96: 79: 76: 35:known to have 33:bacteriophages 15: 13: 10: 9: 6: 4: 3: 2: 1431: 1420: 1417: 1416: 1414: 1407: 1403: 1400: 1399: 1395: 1386: 1382: 1378: 1374: 1369: 1364: 1360: 1356: 1352: 1348: 1344: 1337: 1334: 1329: 1325: 1320: 1315: 1311: 1307: 1303: 1299: 1295: 1288: 1285: 1280: 1276: 1272: 1268: 1264: 1260: 1256: 1252: 1245: 1242: 1237: 1233: 1229: 1225: 1221: 1217: 1210: 1207: 1202: 1198: 1193: 1188: 1184: 1180: 1176: 1172: 1168: 1161: 1158: 1153: 1149: 1145: 1141: 1137: 1133: 1129: 1125: 1121: 1117: 1110: 1107: 1101: 1098: 1093: 1089: 1085: 1081: 1074: 1071: 1066: 1062: 1057: 1052: 1048: 1044: 1040: 1036: 1032: 1025: 1023: 1019: 1014: 1010: 1006: 1002: 997: 992: 988: 984: 980: 973: 970: 965: 961: 957: 953: 949: 945: 941: 937: 930: 927: 922: 918: 913: 908: 904: 900: 896: 892: 888: 880: 878: 876: 874: 870: 865: 861: 855: 852: 847: 843: 837: 834: 829: 825: 819: 816: 804: 800: 794: 791: 786: 782: 777: 772: 768: 764: 760: 756: 752: 745: 742: 737: 733: 728: 723: 718: 713: 709: 705: 701: 694: 692: 690: 688: 684: 679: 673: 665: 661: 657: 653: 649: 645: 638: 635: 630: 626: 621: 616: 612: 608: 604: 600: 596: 589: 586: 581: 577: 573: 569: 565: 561: 557: 553: 546: 543: 538: 534: 529: 524: 519: 514: 510: 506: 503:(1): e16329. 502: 498: 494: 487: 484: 479: 475: 471: 467: 463: 459: 452: 449: 436: 430: 428: 426: 422: 417: 413: 409: 405: 401: 397: 393: 389: 385: 381: 374: 371: 360: 356: 352: 351: 343: 340: 333: 331: 328: 324: 320: 316: 311: 307: 306: 301: 296: 294: 293:phage therapy 290: 286: 285:reporter gene 281: 279: 275: 274: 269: 265: 256: 254: 252: 246: 244: 243:pathogenicity 240: 236: 228: 226: 222: 220: 216: 208: 203: 202: 197: 194: 193: 188: 185: 184: 179: 178: 173: 172: 171: 165: 163: 157: 153: 147: 143: 141: 137: 133: 128: 125: 121: 117: 112: 109: 105: 97: 95: 93: 89: 85: 77: 75: 73: 69: 65: 60: 58: 54: 50: 49: 44: 43: 38: 34: 30: 21: 1406: 1350: 1346: 1336: 1301: 1297: 1287: 1254: 1250: 1244: 1219: 1215: 1209: 1174: 1170: 1160: 1119: 1115: 1109: 1100: 1083: 1079: 1073: 1038: 1034: 986: 982: 972: 939: 935: 929: 894: 890: 863: 854: 845: 836: 827: 818: 806:. Retrieved 802: 793: 758: 754: 744: 707: 703: 672:cite journal 647: 643: 637: 602: 598: 588: 555: 551: 545: 500: 496: 486: 461: 457: 451: 439:. Retrieved 383: 379: 373: 362:, retrieved 349: 342: 327:M. abscessus 326: 318: 315:M. abscessus 314: 309: 305:M. abscessus 303: 297: 288: 282: 277: 271: 260: 257:Applications 247: 232: 223: 218: 215:M. smegmatis 214: 212: 201:Corndogvirus 199: 190: 181: 175: 169: 161: 155: 152:M. smegmatis 151: 140:lytic growth 135: 131: 129: 120:M. smegmatis 119: 115: 113: 108:tuberculosis 103: 101: 91: 83: 81: 68:siphoviridae 61: 53:tuberculosis 46: 40: 37:mycobacteria 28: 26: 650:: 726–729. 441:4 September 310:massiliense 177:Fromanvirus 124:codon usage 1222:(1): 1–6. 334:References 209:Host range 72:myoviridae 1385:248755782 319:abscessus 136:phamilies 98:Diversity 78:Discovery 1413:Category 1377:35568033 1328:31068712 1279:43134099 1271:16033452 1236:16584300 1201:22415006 1065:20064525 1013:14055875 1005:12705866 964:10188307 921:23084079 891:Virology 785:23560716 736:24651299 664:14019331 629:13197609 580:20772051 572:20270730 537:21298013 497:PLOS ONE 478:20528690 408:14469307 264:phasmids 166:Taxonomy 57:lysogeny 1368:9840467 1319:6557439 1192:3312217 1152:9192407 1144:3473289 1124:Bibcode 1056:2830324 956:8459766 912:3518647 776:3641587 727:3961340 620:1620761 528:3029335 505:Bibcode 416:4263411 388:Bibcode 364:24 July 317:subsp. 308:subsp. 278:E. coli 268:cosmids 88:compost 1383:  1375:  1365:  1326:  1316:  1277:  1269:  1234:  1199:  1189:  1150:  1142:  1116:Nature 1092:820285 1090:  1063:  1053:  1011:  1003:  962:  954:  919:  909:  808:10 May 783:  773:  734:  724:  662:  627:  617:  578:  570:  535:  525:  476:  414:  406:  380:Nature 235:mosaic 180:. See 1381:S2CID 1275:S2CID 1148:S2CID 1009:S2CID 960:S2CID 576:S2CID 412:S2CID 132:genes 1373:PMID 1347:Cell 1324:PMID 1267:PMID 1232:PMID 1197:PMID 1171:mBio 1140:PMID 1088:PMID 1061:PMID 1001:PMID 983:Cell 952:PMID 917:PMID 810:2023 781:PMID 732:PMID 678:link 660:PMID 625:PMID 568:PMID 533:PMID 474:PMID 443:2017 404:PMID 366:2021 45:and 1363:PMC 1355:doi 1351:185 1314:PMC 1306:doi 1259:doi 1224:doi 1187:PMC 1179:doi 1132:doi 1120:327 1051:PMC 1043:doi 1039:397 991:doi 987:113 944:doi 907:PMC 899:doi 895:434 771:PMC 763:doi 722:PMC 712:doi 652:doi 615:PMC 607:doi 560:doi 523:PMC 513:doi 466:doi 396:doi 384:191 355:doi 270:in 70:or 1415:: 1379:. 1371:. 1361:. 1349:. 1345:. 1322:. 1312:. 1302:25 1300:. 1296:. 1273:. 1265:. 1255:99 1253:. 1230:. 1220:12 1218:. 1195:. 1185:. 1173:. 1169:. 1146:. 1138:. 1130:. 1118:. 1084:17 1082:. 1059:. 1049:. 1037:. 1033:. 1021:^ 1007:. 999:. 985:. 981:. 958:. 950:. 938:. 915:. 905:. 893:. 889:. 872:^ 862:. 844:. 826:. 801:. 779:. 769:. 759:88 757:. 753:. 730:. 720:. 708:10 706:. 702:. 686:^ 674:}} 670:{{ 648:87 646:. 623:. 613:. 603:44 601:. 597:. 574:. 566:. 556:66 554:. 531:. 521:. 511:. 499:. 495:. 472:. 462:64 460:. 424:^ 410:. 402:. 394:. 382:. 353:, 295:. 245:. 142:. 74:. 27:A 1387:. 1357:: 1330:. 1308:: 1281:. 1261:: 1238:. 1226:: 1203:. 1181:: 1175:3 1154:. 1134:: 1126:: 1094:. 1067:. 1045:: 1015:. 993:: 966:. 946:: 940:7 923:. 901:: 866:. 848:. 830:. 812:. 787:. 765:: 738:. 714:: 680:) 666:. 654:: 631:. 609:: 582:. 562:: 539:. 515:: 507:: 501:6 480:. 468:: 445:. 418:. 398:: 390:: 357:: 204:. 186:.

Index


bacteriophages
mycobacteria
Mycobacterium smegmatis
Mycobacterium tuberculosis
tuberculosis
lysogeny
double-stranded DNA
siphoviridae
myoviridae
compost
tuberculosis
codon usage
lytic growth

Fromanvirus
Mycobacterium virus L5
Timquatrovirus
Corndogvirus
mosaic
horizontal genetic transfer
pathogenicity
Pittsburgh, Pennsylvania
phasmids
cosmids
Escherichia coli
reporter gene
phage therapy
cystic fibrosis
M. abscessus

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