Clostridium difficile phages: Still difficult?

Frontiers in Microbiology

Volumn 5, Issue APR, 2014, Pages

  Hargreaves, Katherine R ^a   Clokie, Martha R J ^a  

^a UNIVERSITY OF LEICESTER   (United Kingdom)

Author keywords

Clostridium difficile; Genomics; Gut pathogen; Lysogeny; Nosocomial; Phage evolution; Phage therapy

Indexed keywords

CLOSTRIDIUM DIFFICILE TOXIN A; CLOSTRIDIUM DIFFICILE TOXIN B; ENDOLYSIN; UNCLASSIFIED DRUG; VIRUS ENZYME;

ARTICLE; BACTERIOPHAGE; BACTERIOPHAGE TYPING; BIOFILM; BIOLOGICAL THERAPY; CLOSTRIDIUM DIFFICILE; CLOSTRIDIUM DIFFICILE INFECTION; CLOSTRIDIUM DIFFICILE PHAGE; COEVOLUTION; GENETIC VARIABILITY; HORIZONTAL GENE TRANSFER; HOST RANGE; HUMAN; INFECTION RESISTANCE; INTESTINE FLORA; LYSOGENIZATION; NONHUMAN; PHAGE THERAPY; RIBOTYPING; TAXONOMY; VIRUS GENOME; VIRUS ISOLATION; VIRUS REPLICATION;

EID: 84899684470     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2014.00184     Document Type: Article

References (117)

1. Abedon, S. T., Kuhl, S. J., Blasdel, B. G., and Kutter, E. M. (2011). Phage treatment of human infections. Bacteriophage 1, 66-85. doi: 10.4161/bact.1.2.15845
2. Al-Nassir, W. N., Sethi, A. K., Li, Y., Pultz, M. J., Riggs, M. M., and Donskey, C. J. (2008). Both oral metronidazole and oral vancomycin promote persistent overgrowth of vancomycin-resistant enterococci during treatment of Clostridium difficile-associated disease. Antimicrob. Agents Chemother. 52, 2403-2406. doi: 10.1128/AAC.00090-08
3. al Saif, N., and Brazier, J. S. (1996). The distribution of Clostridium difficile in the environment of South Wales. J. Med. Microbiol. 45, 133-137. doi: 10.1099/00222615-45-2-133
4. Bacon, A. E., Fekety, R., Schaberg, D. R., and Faix, R. G. (1988). Epidemiology of Clostridium difficile colonization in newborns-results using a bacteriophage typing system. J. Infect. Dis. 158, 349-354. doi: 10.1093/infdis/158.2.349
5. Baumgart, M., Unthan, S., Rueckert, C., Sivalingam, J., Gruenberger, A., Kalinowski, J., et al. (2013). Construction of a prophage-free variant of Corynebacterium glutamicum ATCC 13032 for use as a platform strain for basic research and industrial biotechnology. Appl. Environ. Microbiol. 79, 6006-6015. doi: 10.1128/AEM.01634-13
6. Betts, A., Vasse, M., Kaltz, O., and Hochberg, M. E. (2013). Back to the future: evolving bacteriophages to increase their effectiveness against the pathogen Pseudomonas aeruginosa PAO1. Evol. Appl. 6, 1054-1063. doi: 10.1111/eva.12085
7. Bignell, C., and Thomas, C. M. (2001). The bacterial ParA-ParB partitioning proteins. J. Biotechnol. 91, 1-34. doi: 10.1016/S0168-1656(01)00293-0
8. Bouza, E. (2012). Consequences of Clostridium difficile infection: understanding the healthcare burden. Clin. Microbiol. Infect. 18, 5-12. doi: 10.1111/1469-0691.12064
9. Boyd, E. F. (2012). Bacteriophage-encoded bacterial virulence factors and phage-pathogenicity island interactions. Adv. Virus Res. 82, 91-118. doi: 10.1016/B978-0-12-394621-8.00014-5
10. Brouwer, M. S. M., Roberts, A. P., Hussain, H., Williams, R. J., Allan, E., and Mullany, P. (2013). Horizontal gene transfer converts non-toxigenic Clostridium difficile strains into toxin producers. Nat. Commun. 4:2601. doi: 10.1038/ncomms3601
11. Brüssow, H. (2012). Pseudomonas biofilms, cystic fibrosis, and phage: a silver lining? MBio 3:e00061-12. doi: 10.1128/mBio.00061-12
12. Buckley, A. M., Spencer, J., Candlish, D., Irvine, J. J., and Douce, G. R. (2011). Infection of hamsters with the UK Clostridium difficile ribotype 027 outbreak strain R20291. J. Med. Microbiol. 60, 1174-1180. doi: 10.1099/jmm.0.028514-0
13. Calabi, E., Ward, S., Wren, B., Paxton, T., Panico, M., Morris, H., et al. (2001). Molecular characterization of the surface layer proteins from Clostridium difficile. Mol. Microbiol. 40, 1187-1199. doi: 10.1046/j.1365-2958.2001.02461.x
14. Centers for Disease Control and Prevention (CDC). (2013). Antibiotic Resistance Threats in the United States, 2013. Threat Report. Atlanta: Centers for Disease Control and Prevention. Available at: http://www.cdc.gov/drugresistance/threat-report-2013/pdf/ar-threats-2013-508.pdf
15. Cohen, S. H., Tang, Y. J., and Silva, J. (2000). Analysis of the pathogenicity locus in Clostridium difficile strains. J. Infect. Dis. 181, 659-663. doi: 10.1086/315248
16. Dapa, T., and Unnikrishnan, M. (2013). Biofilm formation by Clostridium difficile. Gut Microbes 4, 397-402. doi: 10.4161/gmic.25862
17. Dei, R. (1989). Observations on phage typing of Clostridium difficile-preliminary evaluation of a phage panel. Eur. J. Epidemiol. 5, 351-354. doi: 10.1007/BF00144837
18. Edwards, P., and Smit, J. (1991). A transducing bacteriophage for Caulobacter crescentus uses the paracrystalline surface layer protein as a receptor. J. Bacteriol. 173, 5568-5572.
19. El-Arabi, T. F., Griffiths, M. W., She, Y.-M., Villegas, A., Lingohr, E. J., and Kropinski, A. M. (2013). Genome sequence and analysis of a broad-host range lytic bacteriophage that infects the Bacillus cereus group. Virol. J. 10:48. doi: 10.1186/1743-422X-10-48
20. Eyre, D. W., Walker, A. S., Griffiths, D., Wilcox, M. H., Wyllie, D. H., Dingle, K. E., et al. (2012). Clostridium difficile mixed infection and reinfection. J. Clin. Microbiol. 50, 142-144. doi: 10.1128/JCM.05177-11
21. Fagan, R. P., and Fairweather, N. F. (2014). Biogenesis and functions of bacterial S-layers. Nat. Rev. Microbiol. 12, 211-222. doi: 10.1038/nrmicro3213
22. Flemming, H.-C., and Wingender, J. (2010). The biofilm matrix. Nat. Rev. Microbiol. 8, 623-633. doi: 10.1038/nrmicro2415
23. Fortier, L.-C., and Moineau, S. (2007). Morphological and genetic diversity of temperate phages in Clostridium difficile. Appl. Environ. Microbiol. 73, 7358-7366. doi: 10.1128/AEM.00582-07
24. Fortier, L.-C., and Sekulovic, O. (2013). Importance of prophages to evolution and virulence of bacterial pathogens. Virulence 4, 354-365. doi: 10.4161/viru.24498
25. Fu, W., Forster, T., Mayer, O., Curtin, J. J., Lehman, S. M., and Donlan, R. M. (2010). Bacteriophage cocktail for the prevention of biofilm formation by Pseudomonas aeruginosa on catheters in an in vitro model system. Antimicrob. Agents Chemother. 54, 397-404. doi: 10.1128/AAC.00669-09
26. Garvey, P., Fitzgerald, G. F., and Hill, C. (1995). Cloning and DNA sequence analysis of 2 abortive infection phage resistance determinants from the lactoccocal plasmid pnp40. Appl. Environ. Microbiol. 61, 4321-4328.
27. George, R. H., Symonds, J. M., Dimock, F., Brown, J. D., Arabi, Y., Shinagawa, N., et al. (1978). Identification of Clostridium difficile as a cause of pseudomembranous colitis. Br. Med. J. 1, 695. doi: 10.1136/bmj.1.6114.695
28. Goh, S., Chang, B., and Riley, T. (2005a). Effect of phage infection on toxin production by Clostridium difficile. J. Med. Microbiol. 54, 129-135. doi: 10.1099/jmm.0.45821-0
29. Goh, S., Riley, T., and Chang, B. (2005b). Isolation and characterization of temperate bacteriophages of Clostridium difficile. Appl. Environ. Microbiol. 71, 1079-1083. doi: 10.1128/AEM.71.2.1079-1083.2005
30. Goh, S., Hussain, H., Chang, B. J., Emmett, W., Riley, T. V., and Mullany, P. (2013). Phage C2 mediates transduction of Tn6215, encoding erythromycin resistance, between Clostridium difficile strains. MBio 4:e00840-13. doi: 10.1128/mBio.00840-13
31. Goh, S., Ong, P., Song, K., Riley, T., and Chang, B. (2007). The complete genome sequence of Clostridium difficile phage phi C2 and comparisons to phi CD119 and inducible prophages of CD630. Microbiology 153, 676-685. doi: 10.1099/mic.0.2006/002436-0
32. Goorhuis, A., Bakker, D., Corver, J., Debast, S., Harmanus, C., Notermans, D., et al. (2008). Emergence of Clostridium difficile infection due to a new hypervirulent strain, polymerase chain reaction ribotype 078. Clin. Infect. Dis. 47, 1162-1170. doi: 10.1086/592257
33. Govind, R., Fralick, J., and Rolfe, R. (2006). Genomic organization and molecular characterization of Clostridium difficile bacteriophage Phi CD119. J. Bacteriol. 188, 2568-2577. doi: 10.1128/JB.188.7.2568-2577.2006
34. Govind, R., Fralick, J., and Rolfe, R. (2011). In vivo lysogenization of a Clostridium difficile bacteriophage Phi CD119. Anaerobe 17, 125-129. doi: 10.1016/j.anaerobe.2011.05.012
35. Govind, R., Vediyappan, G., Rolfe, R., Dupuy, B., and Fralick, J. (2009). Bacteriophage-mediated toxin gene regulation in Clostridium difficile. J. Virol. 83, 12037-12045. doi: 10.1128/JVI.01256-09
36. Hall, I. C., and O'Toole, E. (1935). Intestinal flora in new-born infants: with a description of a new pathogenic anaerobe, Bacillus difficilis. Am. J. Dis. Child. 49, 390-402. doi: 10.1001/archpedi.1935.01970020105010
37. Hanlon, G. W., Denyer, S. P., Olliff, C. J., and Ibrahim, L. J. (2001). Reduction in exopolysaccharide viscosity as an aid to bacteriophage penetration through Pseudomonas aeruginosa biofilms. Appl. Environ. Microbiol. 67, 2746-2753. doi: 10.1128/AEM.67.6.2746-2753.2001
38. Hargreaves, K. R., Anderson, N. J., and Clokie, M. R. J. (2013a). Recovery of viable cyanophages from the sediments of a eutrophic lake at decadal timescales. FEMS Microbiol. Ecol. 83, 450-456. doi: 10.1111/1574-6941.12005
39. Hargreaves, K. R., Colvin, H. V., Patel, K. V., Clokie, J. J. P., and Clokie, M. R. J. (2013b). Genetically diverse Clostridium difficile strains harboring abundant prophages in an estuarine environment. Appl. Environ. Microbiol. 79, 6236-6243. doi: 10.1128/AEM.01849-13
40. Hargreaves, K. R., Kropinski, A. M., and Clokie, M. R. J. (2013c). What does the talking?: quorum sensing signalling genes discovered in a bacteriophage genome. PLoS ONE 9:e85131. doi: 10.1371/journal.pone.0085131
41. Hawkins, C. C., Buggy, B. P., Fekety, R., and Schaberg, D. R. (1984). Epidemiology of colitis induced Clostridium difficile in hamsters-application of a bacteriophage and bacteriocin typing system. J. Infect. Dis. 149, 775-780. doi: 10.1093/infdis/149.5.775
42. He, M., Miyajima, F., Roberts, P., Ellison, L., Pickard, D. J., Martin, M. J., et al. (2012). Emergence and global spread of epidemic healthcare-associated Clostridium difficile. Nat. Genet. 45, 109-113. doi: 10.1038/ng.2478
43. Heap, J. T., Pennington, O. J., Cartman, S. T., Carter, G. P., and Minton, N. P. (2007). The ClosTron: a universal gene knock-out system for the genus Clostridium. J. Microbiol. Methods 70, 452-464. doi: 10.1016/j.mimet.2007.05.021
44. Horgan, M., O'Sullivan, O., Coffey, A., Fitzgerald, G., van Sinderen, D., McAuliffe, O., et al. (2010). Genome analysis of the Clostridium difficile phage Phi CD6356, a temperate phage of the Siphoviridae family. Gene 462, 34-43. doi: 10.1016/j.gene.2010.04.010
45. Hubert, B., Loo, V. G., Bourgault, A.-M., Poirier, L., Dascal, A., Fortin, E., et al. (2007). A portrait of the geographic dissemination of the Clostridium difficile North American pulsed-field type 1 strain and the epidemiology of C. difficile-associated disease in Quebec. Clin. Infect. Dis. 44, 238-244. doi: 10.1086/510391
46. Hughes, G. J., Nickerson, E., Enoch, D. A., Ahluwalia, J., Wilkinson, C., Ayers, R., et al. (2013). Impact of cleaning and other interventions on the reduction of hospital-acquired Clostridium difficile infections in two hospitals in England assessed using a breakpoint model. J. Hosp. Infect. 84, 227-234. doi: 10.1016/j.jhin.2012.12.018
47. Hyman, P., and Abedon, S. T. (2010). Bacteriophage host range and bacterial resistance. Adv. Appl. Microbiol. 70, 217-248. doi: 10.1016/S0065-2164(10)70007-1
48. Janezic, S., Ocepek, M., Zidaric, V., and Rupnik, M. (2012). Clostridium difficile genotypes other than ribotype 078 that are prevalent among human, animal and environmental isolates. BMC Microbiol. 12:48. doi: 10.1186/1471-2180-12-48
49. Johnson, S. (2009). Recurrent Clostridium difficile infection: a review of risk factors, treatments, and outcomes. J. Infect. 58, 403-410. doi: 10.1016/j.jinf.2009.03.010
50. Kelly, D., McAuliffe, O., Ross, R. P., and Coffey, A. (2012). Prevention of Staphylococcus aureus biofilm formation and reduction in established biofilm density using a combination of phage K and modified derivatives. Lett. Appl. Microbiol. 54, 286-291. doi: 10.1111/j.1472-765X.2012.03205
51. Koskella, B., Lin, D. M., Buckling, A., and Thompson J. N. (2012). The costs of evolving resistance in heterogeneous parasite environments. Proc. Biol. Sci. 279, 1896-1903. doi: 10.1098/rspb.2011.2259
52. Kropinski, A. M. (2006). Phage therapy-everything old is new again. Can. J. Infect. Dis. Med. Microbiol. 17, 297-306.
53. Kuijper, E. J., Coignard, B., Tüll, P., ESCMID Study Group for Clostridium difficile, EU Member States, and European Centre for Disease Prevention and Control. (2006). Emergence of Clostridium difficile-associated disease in North America and Europe. Clin. Microbiol. Infect. 12(Suppl. 6), 2-18.
54. Kutter, E., and Sulakvelidze, A. (2004). Bacteriophages: Biology and Applications. Boca Raton, FL: CRC Press.
55. Labrie, S. J., Samson, J. E., and Moineau, S. (2010). Bacteriophage resistance mechanisms. Nat. Rev. Microbiol. 8, 317-327. doi: 10.1038/nrmicro2315
56. Lavigne, R., Darius, P., Summer, E. J., Seto, D., Mahadevan, P., Nilsson, A. S., et al. (2009). Classification of Myoviridae bacteriophages using protein sequence similarity. BMC Microbiol. 9:224. doi: 10.1186/1471-2180-9-224
57. Lavigne, R., Lecoutere, E., Wagemans, J., Cenens, W., Aertsen, A., Schoofs, L., et al. (2013). A Multifaceted study of Pseudomonas aeruginosa shutdown by virulent podovirus LUZ19. MBio 4:e00061-13. doi: 10.1128/mBio.00061-13
58. Lawley, T. D., Croucher, N. J., Yu, L., Clare, S., Sebaihia, M., Goulding, D., et al. (2009). Proteomic and genomic characterization of highly infectious Clostridium difficile 630 spores. J. Bacteriol. 191, 5377-5386. doi: 10.1128/JB.00597-09
59. Libby, D. B., and Bearman, G. (2009). Bacteremia due to Clostridium difficile-review of the literature. Int. J. Infect. Dis. 13, E305-E309. doi: 10.1016/j.ijid.2009.01.014
60. Loo, V. G. (2006). A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality. N. Eng. J. Med. 354, 2200. doi: 10.1056/NEJMx060024
61. Louie, T. J., Cannon, K., Byrne, B., Emery, J., Ward, L., Eyben, M., et al. (2012). Fidaxomicin preserves the intestinal microbiome during and after treatment of Clostridium difficile infection (CDI) and reduces both toxin reexpression and recurrence of CDI. Clin. Infect. Dis. 55, S132-S142. doi: 10.1093/cid/cis338
62. Lu, T. K., and Collins, J. J. (2009). "Engineering synthetic bacteriophage to combat antibiotic-resistant bacteria," in Proceedings of the IEEE 35th Annual Northeast Bioengineering Conference, 2009 (Boston, MA: Institute of Electrical and Electronics Engineers), 1-2.
63. Mahony, D., Bell, P., and Easterbrook, K. (1985). Two bacteriophages of Clostridium difficile. J. Clin. Microbiol. 21, 251-254.
64. Mahony, D. E., Clow, J., Atkinson, L., Vakharia, N., and Schlech, W. F. (1991). Development and application of a multiple typing system for Clostridium difficile. Appl. Environ. Microbiol. 57, 1873-1879.
65. Manges, A. R., Labbe, A., Loo, V. G., Atherton, J. K., Behr, M. A., Masson, L., et al. (2010). Comparative metagenomic study of alterations to the intestinal microbiota and risk of nosocomial Clostridum difficile-associated disease. J. Infect. Dis. 202, 1877-1884. doi: 10.1086/657319
66. Mayer, M., Garefalaki, V., Spoerl, R., Narbad, A., and Meijers, R. (2011). Structure-based modification of a Clostridium difficile-targeting endolysin affects activity and host range. J. Bacteriol. 193, 5477-5486. doi: 10.1128/JB.00439-11
67. Mayer, M., Narbad, A., and Gasson, M. (2008). Molecular characterization of a Clostridium difficile bacteriophage and its cloned biologically active endolysin. J. Bacteriol. 190, 6734-6740. doi: 10.1128/JB.00686-08
68. McDonald, L., Killgore, G., Thompson, A., Owens, R., Kazakova, S., Sambol, S., et al. (2005). An epidemic, toxin gene-variant strain of Clostridium difficile. N. Eng. J. Med. 353, 2433-2441. doi: 10.1056/NEJMoa051590
69. Meaden, S., and Koskella, B. (2013). Exploring the risks of phage application in the environment. Front. Microbiol. 4:8. doi: 10.3389/fmicb.2013.00358
70. Meader, E., Mayer, M., Gasson, M., Steverding, D., Carding, S., and Narbad, A. (2010). Bacteriophage treatment significantly reduces viable Clostridium difficile and prevents toxin production in an in vitro model system. Anaerobe 16, 549-554. doi: 10.1016/j.anaerobe.2010.08.006
71. Meader, E., Mayer, M. J., Steverding, D., Carding, S. R., and Narbad, A. (2013). Evaluation of bacteriophage therapy to control Clostridium difficile and toxin production in an in vitro human colon model system. Anaerobe 22, 25-30. doi: 10.1016/j.anaerobe.2013.05.001
72. Meessen-Pinard, M., Sekulovic, O., and Fortier, L. (2012). Evidence of in vivo prophage induction during Clostridium difficile. Infect. Appl. Environ. Microbiol. 78, 7662-7670. doi: 10.1128/AEM.02275-12
73. Metcalf, D., Avery, B. P., Janecko, N., Matic, N., Reid-Smith, R., and Weese, J. S. (2011). Clostridium difficile in seafood and fish. Anaerobe 17, 85-86. doi: 10.1016/j.anaerobe.2011.02.008
74. Metcalf, D. S., Costa, M. C., Dew, W. M. V., and Weese, J. S. (2010). Clostridium difficile in vegetables, Canada. Lett. Appl. Microbiol. 51, 600-602. doi: 10.1111/j.1472-765X.2010.02933.x
75. Modi, S. R., Lee, H. H., Spina, C. S., and Collins, J. J. (2013). Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome. Nature 499, 219-222. doi: 10.1038/nature12212
76. Moradpour, Z., and Ghasemian, A. (2011). Modified phages: novel antimicrobial agents to combat infectious diseases. Biotechnol. Adv. 29, 732-738. doi: 10.1016/j.biotechadv.2011.06.003
77. Nagy, E., and Foldes, J. (1991). Electron microscopic investigation of lysogeny of Clostridium difficile strains isolated from antibiotic-associated diarrhea cases and from healthy carriers. APMIS 99, 321-326. doi: 10.1111/j.1699-0463.1991.tb05156.x
78. Nale, J., Shan, J., Hickenbotham, P., Fawley, W., Wilcox, M., and Clokie, M. (2012). Diverse temperate bacteriophage carriage in Clostridium difficile 027 strains. PLoS ONE 7:e37263. doi: 10.1371/journal.pone.0037263.0
79. O'Connor, J. R., Lyras, D., Farrow, K. A., Adams, V., Powell, D. R., Hinds, D. R., et al. (2006). Construction and analysis of chromosomal Clostridium difficile mutants. Mol. Microbiol. 61, 1335-1351. doi: 10.1111/j.1365-2958.2006.05315.x
80. O'Neill, G., Ogunsola, F., Brazier, J., and Duerden, B. (1996). Modification of a PCR ribotyping method for application as a routine typing scheme for Clostridium difficile. Anaerobe 2, 205-209. doi: 10.1006/anae.1996.0028
81. Pasquale, V., Romano, V. J., Rupnik, M., Dumontet, S., Ciznar, I., Aliberti, F., et al. (2011). Isolation and characterization of Clostridium difficile from shellfish and marine environments. Folia Microbiol. 56, 431-437. doi: 10.1007/s12223-011-0068-3
82. Peterfreund, G. L., Vandivier, L. E., Sinha, R., Marozsan, A. J., Olson, W. C., Zhu, J., et al. (2012). Succession in the gut microbiome following antibiotic and antibody therapies for Clostridium difficile. PLoS ONE 7:e46966 doi: 10.1371/journal.pone.0046966
83. Public Health England. (2013). Financial Year Counts and Rates of C. difficile Infection by NHS Acute Trust (FY 2007/08-2012/13). Available at: http://www.hpa.org.uk/web/HPAweb&HPAwebStandard/HPAweb_C/1195733750761
84. Purdy, D., O'Keeffe, T. A. T., Elmore, M., Herbert, M., McLeod, A., Bokori-Brown, M., et al. (2002). Conjugative transfer of clostridial shuttle vectors from Escherichia coli to Clostridium difficile through circumvention of the restriction barrier. Mol. Microbiol. 46, 439-452. doi: 10.1046/j.1365-2958.2002.03134.x
85. Ramesh, V., Fralick, J. A., and Rolfe, R. D. (1999). Prevention of Clostridium difficile-induced ileocecitis with bacteriophage. Anaerobe 5, 69-78. doi: 10.1006/anae.1999.0192
86. Rea, M. C., Dobson, A., O'Sullivan, O., Crispie, F., Fouhy, F., Cotter, P. D., et al. (2011). Effect of broad-and narrow-spectrum antimicrobials on Clostridium difficile and microbial diversity in a model of the distal colon. Proc. Natl. Acad. Sci. U.S.A. 108, 4639-4644. doi: 10.1073/pnas.1001224107
87. Rees, C. E. D., and Dodd, C. E. R. (2006). Phage for rapid detection and control of bacterial pathogens in food. Adv. Appl. Microbiol. 59, 159-186. doi: 10.1016/S0065-2164(06)59006-9
88. Roces, C., Wegmann, U., Campelo, A. B., Garcia, P., Rodriguez, A., and Martinez, B. (2013). Lack of the host membrane protease FtsH hinders release of the Lactococcus lactis bacteriophage TP712. J. Gen. Virol. 94, 2814-2818. doi: 10.1099/vir.0.057182-0
89. Rupnik, M. (2007). Is Clostridium difficile-associated infection a potentially zoonotic and foodborne disease? Clin. Microbiol. Infect. 13, 457-459. doi: 10.1111/j.1469-0691.2007.01687.x
90. Rupnik, M., Wilcox, M. H., and Gerding, D. N. (2009). Clostridium difficile infection: new developments in epidemiology and pathogenesis. Nat. Rev. Microbiol. 7, 526-536. doi: 10.1038/nrmicro2164
91. Schallehn, G. (1985). Clostridium sordellii bacteriophage active on Clostridium difficile. Lett. Appl. Microbiol. 1, 71-74. doi: 10.1111/j.1472-765X.1985.tb01492.x
92. Schuch, R., and Fischetti, V. A. (2009). The secret life of the anthrax agent Bacillus anthracis: bacteriophage-mediated ecological adaptations. PLoS ONE 4:e6532. doi: 10.1371/journal.pone.0006532
93. Scott, A. E., Timms, A. R., Connerton, P. L., Carrillo, C. L., Radzum, K. A., and Connerton, I. F. (2007). Genome dynamics of Campylobacter jejuni in response to bacteriophage predation. PLoS Pathog. 3:e119. doi: 10.1371/journal.ppat.0030119
94. Sebaihia, M., Wren, B., Mullany, P., Fairweather, N., Minton, N., Stabler, R., et al. (2006). The multidrug-resistant human pathogen Clostridium difficile has a highly mobile, mosaic genome. Nat. Genet. 38, 779-786. doi: 10.1038/ng1830
95. Sekulovic, O., Garneau, J. R., Neron, A., and Fortier, L.-C. (2014). Characterization of temperate phages infecting Clostridium difficile isolates from human and animal origin. Appl. Environ. Microbiol. doi: 10.1128/AEM.00237-14 [Epub ahead of print].
96. Sekulovic, O., Meessen-Pinard, M., and Fortier, L.-C. (2011). Prophage-stimulated toxin production in Clostridium difficile NAP1/027 lysogens. J. Bacteriol. 193, 2726-2734. doi: 10.1128/JB.00787-10
97. Sell, T., Schaberg, D., and Fekety, F. (1983). Bacteriophage and bacteriocin typing scheme for Clostridium difficile. J. Clin. Microbiol. 17, 1148-1152.
98. Shan, J., Patel, K. V., Hickenbotham, P., Nale, J., Hargreaves, K. R., and Clokie, M. R. (2012). Prophage carriage and diversity within clinically relevant strains of Clostridium difficile. Appl. Environ. Microbiol. 78, 6027-6034. doi: 10.1128/AEM.01311-12
99. Sievers, F., Wilm, A., Dineen, D., Gibson, T. J., Karplus, K., Li, W., et al. (2011). Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol. Syst. Biol. 7:539. doi: 10.1038/msb.2011.75
100. Siringan, P., Connerton, P. L., Payne, R. J. H., and Connerton, I. F. (2011). Bacteriophage-mediated dispersal of Campylobacter jejuni biofilms. Appl. Environ. Microbiol. 77, 3320-3326. doi: 10.1128/AEM.02704-10
101. Smillie, C. S., Smith, M. B., Friedman, J., Cordero, O. X., David, L. A., and Alm, E. J. (2011). Ecology drives a global network of gene exchange connecting the human microbiome. Nature 480, 241-244. doi: 10.1038/nature10571
102. Stabler, R., He, M., Dawson, L., Martin, M., Valiente, E., Corton, C., et al. (2009). Comparative genome and phenotypic analysis of Clostridium difficile 027 strains provides insight into the evolution of a hypervirulent bacterium. Genome Biol. 10:R102. doi: 10.1186/gb-2009-10-9-r102
103. Stern, A., and Sorek, R. (2011). The phage-host arms race: shaping the evolution of microbes. Bioessays 33, 43-51. doi: 10.1002/bies.201000071
104. Stewart, P. S., and Costerton, J. W. (2001). Antibiotic resistance of bacteria in biofilms. Lancet 358, 135-138. doi: 10.1016/S0140-6736(01)05321-1
105. Sullivan, M. J., Petty, N. K., and Beatson, S. A. (2011). Easyfig: a genome comparison visualizer. Bioinformatics 27, 1009-1010. doi: 10.1093/bioinformatics/btr039
106. Surawicz, C. M., Brandt, L. J., Binion, D. G., Ananthakrishnan, A. N., Curry, A. N., Gilligan, P. H., et al. (2013). Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. Am. J. Gastroenterol. 108, 478-498. doi: 10.1038/ajg.2013.4
107. Tan, K. S., Wee, B. Y., and Song, K. P. (2001). Evidence for holin function of tcdE gene in the pathogenicity of Clostridium difficile. J. Med. Microbiol. 50, 613-619.
108. UoL. (2013). Bacteria-Eating viruses 'magic bullets in the war on superbugs.' Press Release. Available at: http://www2.le.ac.uk/offices/press/press-releases/2013/october/bacteria-eating-viruses-2018magic-bullets-in-the-war-on-superbugs2019 (accessed October 17, 2013).
109. Ventura, M., Zomer, A., Canchaya, C., O'Connell-Motherway, M., Kuipers, O., Turroni, F., et al. (2007). Comparative analyses of prophage-like elements present in two Lactococcus lactis strains. Appl. Environ. Microbiol. 73, 7771-7780. doi: 10.1128/AEM.01273-07
110. Volozhantsev, N. V., Oakley, B. B., Morales, C. A., Verevkin, V. V., Bannov, V. A., Krasilnikova, V. M., et al. (2012). Molecular characterization of podoviral bacteriophages virulent for Clostridium perfringens and their comparison with members of the Picovirinae. PLoS ONE 7:e38283. doi: 10.1371/journal.pone.0038283
111. Vonberg, R. P., Kuijper, E. J., Wilcox, M. H., Barbut, F., Tull, P., Gastmeier, P., et al. (2008). Infection control measures to limit the spread of Clostridium difficile. Clin. Microbiol. Infect. 14, 2-20. doi: 10.1111/j.1469-0691.2008.01992
112. Wilcox, M. H., Shetty, N., Fawley, W. N., Shemko, M., Coen, P., Birtles, A., et al. (2012). Changing epidemiology of Clostridium difficile infection following the introduction of a national ribotyping-based surveillance scheme in England. Clin. Infect. Dis. 55, 1056-1063. doi: 10.1093/cid/cis614
113. Williams, R., Meader, E., Mayer, M., Narbad, A., Roberts, A. P., and Mullany, P. (2013). Determination of the attP and attB sites of phage phi CD27 from Clostridium difficile NCTC 12727. J. Med. Microbiol. 63, 1439-1443. doi: 10.1099/jmm.0.058651-0
114. Xia, G., Corrigan, R. M., Winstel, V., Goerke, C., Gruendling, A., and Peschel, A. (2011). Wall teichoic acid-dependent adsorption of staphylococcal siphovirus and myovirus. J. Bacteriol. 193, 4006-4009. doi: 10.1128/JB.01412-10
115. Zhang, Q.-G., and Buckling, A. (2012). Phages limit the evolution of bacterial antibiotic resistance in experimental microcosms. Evol. Appl. 5, 575-582. doi: 10.1111/j.1752-4571.2011.00236.x
116. Zidaric, V., Beigot, S., Lapajne, S., and Rupnik, M. (2010). The occurrence and high diversity of Clostridium difficile genotypes in rivers. Anaerobe 16, 371-375. doi: 10.1016/j.anaerobe.2010.06.001
117. Zucca, M., Scutera, S., and Savoia, D. (2013). Novel avenues for Clostridium difficile infection drug discovery. Expert. Opin. Drug Discov. 8, 459-477. doi: 10.1517/17460441.2013.770466