Comparative Genomics of Enterococcus Faecium Bacteriophages


  • Ashwag Shami Princess Nourah bint Abdulrahman University‬, Riyadh, Saudi Arabia ‬‬‬‬‬
  • Malcolm Horsburgh The university of Liverpool, Liverpool, UK


E. faecium, Prophages, Enterococcus, Comparative Genomics.


Temperate bacteriophages are known to be important drivers of genome plasticity in E.  faecium species. The diversity of prophages and their relationship between was investigated after locating 56 prophage elements containing integrase and lysin genes encoded in the 139 publicly available E.  faecium genomes by the end of 2014. Comparative analysis of the seprophages identified eight sequence types, which differed in size and gene content. The prophage genomes comprised between 17 to 72 ORFs and their size ranged from 13.9  to  55.1  kb with 35%  to  37.9% average  G+C  content. Based on alignment analyses of the major functional proteins encoded in the prophage genomes (integrase, terminaselarge subunit, tail protein and holin) each was assigned a sequence type. All of the prophage integrases were identified to be tyrosine  (XerC) recombinases  and  many  of  their  respective attP/attR sequences  were  identified. The mosaic nature of E.  faecium prophage genome sequence types supports previous hypotheses that extensive genetic recombination drives chimeric phage types.


[1] Clark, P. and Clark, A. A Bacteriophage Active Against a Virulent Hemolytic Streptococcus. Experimental Biology and Medicine, 24(7), pp.635-639(1927).
[2] Evans, A. The Prevalence Of Streptococcus Bacteriophage. Science, 80(2063), pp.40-41 (1934).
[3] Duerkop BA, Palmer KL, Horsburgh MJ. Enterococcal Bacteriophages and Genome Defense. Feb 11. In: Gilmore MS, Clewell DB, Ike Y, et al., editors. Enterococci: From Commensals to Leading Causes of Drug Resistant Infection [Internet]. Boston: Massachusetts Eye and Ear Infirmary; 2014-. Available from: (2014)
[4] van Schaik, W., J. Top, D. R. Riley, J. Boekhorst, J. E. Vrijenhoek, C. M. Schapendonk, A. P. Hendrickx, I. J. Nijman, M. J. Bonten, H. Tettelin and R. J. Willems. "Pyrosequencing-based comparative genome analysis of the nosocomial pathogen Enterococcus faecium and identification of a large transferable pathogenicity island." BMC Genomics 11: 239 (2010).
[5] Brede, D., Snipen, L., Ussery, D., Nederbragt, A. and Nes, I. Complete Genome Sequence of the Commensal Enterococcus faecalis 62, Isolated from a Healthy Norwegian Infant. Journal of Bacteriology, 193(9), pp.2377-2378 (2011).
[6] Mazaheri Nezhad Fard, R., M. D. Barton and M. W. Heuzenroeder. "Novel Bacteriophages in Enterococcus spp." Curr Microbiol 60(6): 400-406 (2010).
[7] Yasmin, A., J. G. Kenny, J. Shankar, A. C. Darby, N. Hall, C. Edwards and M. J. Horsburgh. "Comparative genomics and transduction potential of Enterococcus faecalis temperate bacteriophages." J Bacteriol 192(4): 1122-1130 (2010).
[8] Galloway-Pena, J., J. H. Roh, M. Latorre, X. Qin and B. E. Murray. "Genomic and SNP analyses demonstrate a distant separation of the hospital and community-associated clades of Enterococcus faecium." PLoS One 7(1): e30187 (2012).
[9] Wang, Y., W. Wang, Y. Lv, W. Zheng, Z. Mi, G. Pei, X. An, X. Xu, C. Han, J. Liu, C. Zhou and Y. Tong. "Characterization and complete genome sequence analysis of novel bacteriophage IME-EFm1 infecting Enterococcus faecium." J Gen Virol 95(Pt 11): 2565-2575 (2014).
[10] Adriaenssens, E. M., R. Edwards, J. H. E. Nash, P. Mahadevan, D. Seto, H.-W. Ackermann, R. Lavigne and A. M. Kropinski. "Integration of genomic and proteomic analyses in the classification of the Siphoviridae family." Virology (2014).
[11] Rohwer, F. and Edwards, R.. The Phage Proteomic Tree: a Genome-Based Taxonomy for Phage. Journal of Bacteriology, 184(16), pp.4529-4535 (2002).
[12] Lima-Mendez, G., J. Van Helden, A. Toussaint and R. Leplae. "Reticulate representation of evolutionary and functional relationships between phage genomes." Mol Biol Evol 25(4): 762-777 (2008).
[13] Matos, R. C., N. Lapaque, L. Rigottier-Gois, L. Debarbieux, T. Meylheuc, B. Gonzalez-Zorn, F. Repoila, F. Lopes Mde and P. Serror. "Enterococcus faecalis prophage dynamics and contributions to pathogenic traits." PLoS Genet 9(6): e1003539 (2013).
[14] Juhala, R. J., M. E. Ford, R. L. Duda, A. Youlton, G. F. Hatfull and R. W. Hendrix. "Genomic sequences of bacteriophages HK97 and HK022: pervasive genetic mosaicism in the lambdoid bacteriophages." J Mol Biol 299(1): 27-51 (2000).
[15] Villion, M. Bacteriophages of Lactobacillus. Frontiers in Bioscience, Volume(14), p.1661 (2009).
[16] Tang, F., A. Bossers, F. Harders, C. Lu and H. Smith. "Comparative genomic analysis of twelve Streptococcus suis (pro)phages." Genomics 101(6): 336-344(2013).
[17] Johnson, A., B. J. Meyer and M. Ptashne. "Mechanism of action of the cro protein of bacteriophage lambda." Proc Natl Acad Sci U S A 75(4): 1783-1787(1978).
[18] Groth, A. and Calos, M. Phage Integrases: Biology and Applications. Journal of Molecular Biology, 335(3), pp.667-678 (2004).
[19] Park, M. O., K. H. Lim, T. H. Kim and H. I. Chang. "Characterization of site-specific recombination by the integrase MJ1 from enterococcal bacteriophage phiFC1." J Microbiol Biotechnol 17(2): 342-347 (2007).
[20] Hatfull, G. F., D. Jacobs-Sera, J. G. Lawrence, W. H. Pope, D. A. Russell, C. C. Ko, R. J. Weber, M. C. Patel, K. L. Germane, R. H. Edgar, N. N. Hoyte, C. A. Bowman, A. T. Tantoco, E. C. Paladin, M. S. Myers, A. L. Smith, M. S. Grace, T. T. Pham, M. B. O'Brien, A. M. Vogelsberger, A. J. Hryckowian, J. L. Wynalek, H. Donis-Keller, M. W. Bogel, C. L. Peebles, S. G. Cresawn and R. W. Hendrix. "Comparative genomic analysis of 60 Mycobacteriophage genomes: genome clustering, gene acquisition, and gene size." J Mol Biol 397(1): 119-143 (2010).
[21] Goerke, C., R. Pantucek, S. Holtfreter, B. Schulte, M. Zink, D. Grumann, B. M. Broker, J. Doskar and C. Wolz . "Diversity of prophages in dominant Staphylococcus aureus clonal lineages." J Bacteriol 191(11): 3462-3468(2009).
[22] Kutter, E. and A. Sulakvelidze. Bacteriophages: Biology and Applications: Molecular Biology and Applications. Boca Raton, CRC Press (2005).
[23] Hamada, K., Fujisawa, H. and Minagawa, T. A defined in vitro system for packaging of bacteriophage T3 DNA. Virology, 151(1), pp.119-123 (1986).
[24] Veesler, D. and Cambillau, C. A Common Evolutionary Origin for Tailed-Bacteriophage Functional Modules and Bacterial Machineries. Microbiology and Molecular Biology Reviews, 75(3), pp.423-433 (2011).
[25] Fokine, A. and Rossmann, MMolecular architecture of tailed double-stranded DNA phages. Bacteriophage, 4(2), p.e28281 (2014).
[26] Bernhardt, T. G., I. N. Wang, D. K. Struck and R. Young ."Breaking free: "protein antibiotics" and phage lysis." Res Microbiol 153(8): 493-501.
[27] Wang, I. N., D. L. Smith and R. Young (2000). "Holins: the protein clocks of bacteriophage infections." Annu Rev Microbiol 54: 799-825 (2002).
[28] Canchaya, C., Proux, C., Fournous, G., Bruttin, A. and Brussow, H. Prophage Genomics. Microbiology and Molecular Biology Reviews, 67(3), pp.473-473 2003).
[29] Durmaz, E. and T. R. Klaenhammer ."Genetic analysis of chromosomal regions of Lactococcus lactis acquired by recombinant lytic phages." Appl Environ Microbiol 66(3): 895-903(2000).
[30] Botstein, D. "A theory of modular evolution for bacteriophages." Ann N Y Acad Sci 354: 484-490 (1980).
[31] Wang, X., Y. Kim, Q. Ma, S. H. Hong, K. Pokusaeva, J. M. Sturino and T. K. Wood "Cryptic prophages help bacteria cope with adverse environments." Nat Commun 1: 147(2010).
[32] Ubeda, C., E. Maiques, P. Barry, A. Matthews, M. A. Tormo, I. Lasa, R. P. Novick and J. R. Penades."SaPI mutations affecting replication and transfer and enabling autonomous replication in the absence of helper phage." Mol Microbiol 67(3): 493-503(2008)..
[33] Pedulla, M., Ford, M., Karthikeyan, T., Houtz, J., Hendrix, R., Hatfull, G., Poteete, A., Gilcrease, E., Winn-Stapley, D. and Casjens, S. Corrected Sequence of the Bacteriophage P22 Genome. Journal of Bacteriology, 185(4), pp.1475-1477 (2003).




How to Cite

Shami, A., & Horsburgh, M. (2016). Comparative Genomics of Enterococcus Faecium Bacteriophages. American Scientific Research Journal for Engineering, Technology, and Sciences, 26(1), 69–90. Retrieved from