Chapter 22 : Use of Phages in Therapy and Bacterial Detection

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Use of Phages in Therapy and Bacterial Detection, Page 1 of 2

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The continued emergence of drug-resistant bacteria combined with the threat of bioterrorism necessitates a renewed effort to develop rapid detection methods and novel treatment strategies for infectious diseases. Bacteriophages may provide a viable option. The use of bacteriophages to treat infectious disease followed shortly after their discovery independently in 1915 by the English bacteriologist and physician Frederick Twort and in 1917 by the French-Canadian bacteriologist Félix d’Herelle. Earlier studies demonstrated the highly effective role of the innate immune system in the rapid removal of phages from the circulatory system, thereby decreasing the efficacy of intravenously injected phages. The results of independent experiments passing phage lambda through 10 successive cycles in mice were two mutant phages that were able to evade entrapment by the reticuloendothelium system. Supernatants were tested for phages with lytic activity, and one phage, designated øMR11, was selected based on its broad host range. Although toxin genes are an important consideration, they are by no means the only virulence factor encoded by phages. The potential for treating infectious diseases with phages has been pursued since their discovery, but for the reasons outlined in this chapter, phage therapy is not currently accepted in Western medicine. Phages can also be used in the clinical setting as tools for detecting specific bacteria from patient samples and for the rapid identification of antibiotic-resistant bacterial strains.

Citation: McKinstry M, Edgar R. 2005. Use of Phages in Therapy and Bacterial Detection, p 430-440. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch22

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Tumor Necrosis Factor alpha
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Image of FIGURE 1

Approved antibacterial agents, 1983–2004. The graph shows the numbers of new antibacterial agents approved in the United States for the given time frames. Modified from The Infectious Diseases Society of America website (www.idsociety.org) with permission.

Citation: McKinstry M, Edgar R. 2005. Use of Phages in Therapy and Bacterial Detection, p 430-440. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch22
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Image of FIGURE 2

Bacterial resistance spread, 1980–2003. The chart shows increases in rates of resistance for three bacteria that are of concern to public health officials, i.e., methicillin-resistant (MRSA), vancomycin-resistant enterococci (VRE), and fluoroquinolone-resistant (FQRP). Data were collected from hospital intensive care units participating in the National Nosocomial Infections Surveillance System, a component of the Centers for Disease Control. Modified fromThe Infectious Diseases Society of America website (www.idsociety. Org) with permission.

Citation: McKinstry M, Edgar R. 2005. Use of Phages in Therapy and Bacterial Detection, p 430-440. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch22
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Image of FIGURE 3

Protective effects in mice of delayed administration of bacteriophage ϕMR11. Purified ϕMR11 (MOI, 200) was administered to five mice at the various time intervals indicated, after a challenge with S. aureus SA37 (8 × 10 cells). One milliliter of phage-free brain heart infusion broth supplemented with 20 mM MgCl and 20 mM CaCl was injected into mice as a control. Survival rates were determined after 1 (A) and 7 (B) days. Shaded and hatched columns represent the phage-treated and untreated mouse groups, respectively. Asterisks signify statistically significant differences compared with the controls. *, P < 0.05; **, P < 0.01; and ***, P < 0.002. Modified from with permission of the publisher.

Citation: McKinstry M, Edgar R. 2005. Use of Phages in Therapy and Bacterial Detection, p 430-440. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch22
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Image of FIGURE 4

Dose effect of phage ENB6 on rescuing mice from lethal VRE bacteremia. Each bar indicates the state of health of mice after i. p. administration of the minimum lethal dose of VRE followed by a single dose of phage at the indicated concentration 45 min after the bacterial challenge. The group on the far right (four mice) was an untreated control group, given SM buffer i. p. instead of phage. The group on the far left (two animals) was a phage control group, injected only with phage (at the high dose) and not infected with bacteria in order to determine if the phage preparation itself produced adverse effects in mice ( ).

Citation: McKinstry M, Edgar R. 2005. Use of Phages in Therapy and Bacterial Detection, p 430-440. In Waldor M, Friedman D, Adhya S (ed), Phages. ASM Press, Washington, DC. doi: 10.1128/9781555816506.ch22
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1. Arakawa, Y.,, Y. Ike,, M. Nagasawa,, N. Shibata,, Y. Doi,, K. Shibayama,, T. Yagi,, and T. Kurata. 2000. Trends in antimicrobial-drug resistance in Japan. Emerg. Infect. Dis. 6:18.
2. Banaiee, N.,, M. Bobadilla-Del-Valle,, S. Bardarov, Jr.,, P. F. Riska,, P. M. Small,, A. Ponce-De-Leon,, W. R. Jacobs, Jr.,, G. F. Hatfull,, and J. Sifuentes-Osornio. 2001. Luciferase reporter mycobacteriophages for detection, identification, and antibiotic susceptibility testing of Mycobacterium tuberculosis in Mexico. J. Clin. Microbiol. 39:38833888.
3. Barrow, P. A.,, and J. S. Soothill. 1997. Bacteriophage therapy and prophylaxis: rediscovery and renewed assessment of potential. Trends Microbiol. 5:268271.
4. Biswas, B.,, S. Adhya,, P. Washart,, B. Paul,, A. N. Trostel,, B. Powell,, R. Carlton,, and C. Merril. 2002. Bacteriophage therapy rescues mice bacteremic from a clinical isolate of vancomycin-resistant Enterococcus faecium. Infect. Immun. 70:204210.
5. Blasco, R.,, M. J. Murphy,, M. F. Sanders,, and D. J. Squirrell. 1998. Specific assays for bacteria using phage mediated release of adenylate kinase. J.Appl. Microbiol. 84:661666.
6. Boratynski, J.,, D. Syper,, B. Weber-Dabrowska,, M. Lusiak-Szelachowska,, G. Pozniak,, and A. Gorski. 2004. Preparation of endotoxin-free bacteriophages. Cell. Mol. Biol. Lett. 9:253259.
7. Carrera, M. R.A.,, G. F. Kaufmann,, J. M. Mee,, M. M. Meijler,, and G. F. Koob. 2004. Treating cocaine addiction with viruses. Proc. Natl.Acad. Sci. USA 101:1041610421.
8. Carrera, M. R. A.,, J. A. Ashley,, B. Zhou,, P. Wirsching,, G. F. Koob,, and K. D. Janda. 2000. Cocaine vaccines: antibody protection against relapse in a rat model. Proc. Natl.Acad. Sci. USA 97:62026206.
9. Chapman, P.A.,, A. T. Cerdan Malo,, C.A. Siddons,, and M. A. Harkin. 1997. Use of a commercial enzyme immunoassay and confirmation system for detecting Escherichia coli O157 in bovine fecal samples.Appl. Environ. Microbiol.63:25492553.
10. Chibani-Chennoufi, S.,, J. Sidoti,, A. Bruttin,, E. Kutter,, S. Sarker,, and H. Brussow. 2004. In vitro and in vivo bacteriolytic activities of Escherichia coli phages: implications for phage therapy. Antimicrob. Agents Chemother. 48:25582569.
11. del Mar Lleò, M.,, B. Bonato,, C. Signoretto,, and P. Canepari. 2003. Vancomycin resistance is maintained in enterococci in the viable but nonculturable state and after division is resumed. Antimicrob. Agents Chemother. 47:11541156.
12. Enright, M. C.,, D. A. Robinson,, G. Randle,, E. J. Feil,, H. Grundmann,, and B. G. Spratt. 2002. The evolutionary history of methicillinresistant Staphylococcus aureus (MRSA). Proc. Natl. Acad. Sci. USA 99:76877692.
13. Farr, B. M. 2002. Mupirocin to prevent S. aureus infections. N. Engl. J. Med. 346:19051906.
14. Frenkel, D.,, and B. Solomon. 2002. Filamentous phage as vector-mediated antibody delivery to the brain. Proc. Natl.Acad. Sci. USA 99:56755679.
15. Gali, N.,, J. Dominguez,, S. Blanco,, C. Prat,, M. D. Quesada,, L. Matas,, and V. Ausina. 2003. Utility of an in-house mycobacteriophage-based assay for rapid detection of rifampin resistance in Mycobacterium tuberculosis clinical isolates. J. Clin. Microbiol. 41:26472649.
16. Geier, M. R.,, M. E. Trigg,, and C. R. Merril. 1973. The fate of bacteriophage lambda in nonimmune germfree mice. Nature 246:221222.
17. Goodridge, L.,, J. Chen,, and M. Griffiths. 1999. The use of a fluorescent bacteriophage assay for detection of Escherichia coli O157:H7 in inoculated ground beef and raw milk. Int. J. Food. Microbiol. 47:4350.
18. Goodridge, L.,, J. Chen,, and M. Griffiths. 1999. Development and characterization of a fluorescent-bacteriophage assay for detection of Escherichia coli O157:H7. Appl. Environ. Microbiol. 65:13971404.
19.Hagens S., A. Habel, U. von Ashen, A. von Gambian, and U. Blasé. 2004. Therapy of experimental Pseudomonas infections with a nonreplicating genetically modified phage. Antimicrob. Agents Chemother. 48:38173822.
20. Ho, K. 2001. Bacteriophage therapy for bacterial infections. Perspect. Biol. Med. 44:116.
21. Jay, M. T.,, V. Garrett,, J. C. Mohle-Boetani,, M. Barros,, J. A. Farrar,, R. Rios,, S. Abbott,, R. Sowadsky,, K. Komatsu,, R. Mandrell,, J. Sobel,, and S. B. Werner. 2004. Amultistate outbreak of Escherichia coli O157:H7 infection linked to consumption of beef tacos at a fast-food restaurant chain. Clin. Infect. Dis. 39:17.
22. Larocca, D.,, M.A. Burg,, K. Jensen-Pergakes,, E. P. Ravey,, A. M. Gonzalez,, and A. Baird. 2002. Evolving phage vectors for cell targeted gene delivery. Curr. Pharm. Biotechnol. 3:4557.
23. Leeb, M. 2004. Ashot in the arm. Nature 431:892893.
24. Levin, B. R.,, and J. J. Bull. 2004. Population and evolutionary dynamics of phage therapy. Nat. Rev. Microbiol. 2:166173.
25. Lewis, S. Arrowsmith. 1925. Harcourt Brace, New York, N. Y.
26. Matsuzaki, S.,, M. Yasuda,, H. Nishikawa,, M. Kuroda,, T. Ujihara,, T. Shuin,, Y. Shen,, Z. Jin,, S. Fujimoto,, M. D. Nasimuzzaman,, H. Wakiguchi,, S. Sugihara,, T. Sugiura,, S. Koda,, A. Muraoka,, and S. Imai. 2003. Experimental protection of mice against lethal Staphylococcus aureus infection by novel bacteriophage ΦMR11. J. Infect. Dis. 187:613624.
27. McNerney, R.,, B. S. Kambashi,, J. Kinkese,, R. Tembwe,, and P. Godfrey-Faussett. 2004. Development of a bacteriophage phage replication assay for diagnosis of pulmonary tuberculosis. J. Clin. Microbiol. 42:21152120.
28. Merril, C. R.,, B. Biswas,, R. Carlton,, N. C. Jensen,, G. J. Creed,, S. Zullo,, and S. Adhya. 1996. Long-circulating bacteriophage as antibacterial agents. Proc. Natl.Acad. Sci. USA 93:31883192.
29. Merril, C. R.,, D. Scholl,, and S. L. Adhya. 2003. The prospect for bacteriophage therapy in Western medicine. Nat. Rev. Drug Discov. 2:489497.
30.Neufeld T., A. Schwartz-Mittelmann, D. Biran, E. Z. Ron, and J. Rishpon. 2003. Combined phage typing and amperometric detection of released enzymatic activity for the specific identification and quantification of bacteria. Anal. Chem. 75:580585.
31. Nutt, D.,, and A. Lingford-Hughes. 2004. Infecting the brain to stop addiction? Proc. Natl.Acad. Sci. USA 101:1119311194.
32. Oda, M.,, M. Morita,, H. Unno,, and Y. Tanji. 2004. Rapid detection of Escherichia coli O157:H7 by using green fluorescent protein-labeled PP01 bacteriophage. Appl. Environ. Microbiol. 70:527534.
33. Payne, R. J.,, and V. A. A. Jansen. 2003. Pharmacokinetic principles of bacteriophage therapy. Clin. Pharmacokinet. 42:315325.
34. Perencevich, E. N.,, D. N. Fisman,, M. Lipsitch,, A. D. Harris,, J. G. Morris, Jr., and D. L. Smith. 2004. Projected benefits of active surveillance for vancomycin-resistant enterococci in intensive care units. Clin. Infect. Dis. 38:11081115.
35.Report of the Council on Pharmacy and Chemistry. 1936. Phagoid-staphylococcus, phagoid-bacillus colon, phagoid-streptococcus hemolyticus and other bacteriophage preparations of the Phagoid Laboratories, Inc., not acceptable for N. N. R. JAMA 106:922923.
36. Smith, H. W.,, and M. B. Huggins. 1982. Successful treatment of experimental Escherichia coli infection in mice using phage: its general superiority over antibiotics. J. Gen. Microbiol. 128:307318.
37. Spellberg, B.,, J. H. Powers,, E. P. Brass,, L. G. Miller,, and J. E. Edwards, Jr. 2004. Trends in antimicrobial drug development: implications for the future. Clin. Infect. Dis. 38:12791286.
38. Sulakvelidze, A.,, Z. Alavidze,, and J. G. Morris, Jr. 2001. Bacteriophage therapy. Antimicrob. Agents Chemother. 45:649659.
39.Summers, W. C. 1999. Felix d’Herelle and the Origins of Molecular Biology. Yale University Press, New Haven, Conn.
40.Summers, W. C. 2001. Bacteriophage therapy. Annu. Rev. Microbiol. 55:437451.
41. Wada, T.,, S. Maeda,, A. Tamaru,, S. Imai,, A. Hase,, and K. Kobayashi. 2004. Dual-probe assay for rapid detection of drug-resistant Mycobacterium tuberculosis by real-time PCR. J. Clin. Microbiol. 42:52775285.
42. Wagner, P. L.,, and M. K. Waldor. 2002. Bacteriophage control of bacterial virulence. Infect. Immun. 70:39853993.
43. Weld, R. J.,, C. Butts,, and J. A. Heinemann. 2004. Models of phage growth and their applicability to phage therapy. J. Theor. Biol. 227:111.
44. Wenzel, R. P. 2004. The antibiotic pipeline—challenges, costs, and values. N. Engl. J. Med. 351: 523526.
45. Wong, H. C.,, and P. Wang. 2004. Induction of viable but nonculturable state in Vibrio parahaemolyticus and its susceptibility to environmental stresses. J.Appl. Microbiol. 96:359366.
46. Wu, Y.,, L. Brovko,, and M. W. Griffiths. 2001. Influence of phage population on the phagemediated bioluminescent adenylate kinase (AK) assay for detection of bacteria. Lett.Appl. Microbiol. 33:311315.
47. Zhang, Y. 2005. The magic bullets and tuberculosis drugtargets.Annu. Rev. Pharmacol. Toxicol.45:529564.

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