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. 2015 Feb 5;30(1):26–32. doi: 10.1007/s12250-014-3549-0

Phage lytic enzymes: a history

David Trudil 1,✉
PMCID: PMC8200920  PMID: 25662888

Abstract

There are many recent studies regarding the efficacy of bacteriophage-related lytic enzymes: the enzymes of ‘bacteria-eaters’ or viruses that infect bacteria. By degrading the cell wall of the targeted bacteria, these lytic enzymes have been shown to efficiently lyse Gram-positive bacteria without affecting normal flora and non-related bacteria. Recent studies have suggested approaches for lysing Gram-negative bacteria as well (Briersa Y, et al., 2014). These enzymes include: phage-lysozyme, endolysin, lysozyme, lysin, phage lysin, phage lytic enzymes, phageassociated enzymes, enzybiotics, muralysin, muramidase, virolysin and designations such as Ply, PAE and others. Bacteriophages are viruses that kill bacteria, do not contribute to antimicrobial resistance, are easy to develop, inexpensive to manufacture and safe for humans, animals and the environment. The current focus on lytic enzymes has been on their use as anti-infectives in humans and more recently in agricultural research models. The initial translational application of lytic enzymes, however, was not associated with treating or preventing a specific disease but rather as an extraction method to be incorporated in a rapid bacterial detection assay (Bernstein D, 1997).The current review traces the translational history of phage lytic enzymes-from their initial discovery in 1986 for the rapid detection of group A streptococcus in clinical specimens to evolving applications in the detection and prevention of disease in humans and in agriculture.

Keywords: bacteriophage, phage lytic enzymes, translational application, lysin

Footnotes

ORCID: 0000-0002-4114-8138

References

  1. Abedon ST. Bacteriophage prehistory: is or is not Hankin, 1896, a phage reference? Bacteriophage. 2011;1:174–178. doi: 10.4161/bact.1.3.16591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Abedon ST, Kuhl SJ, Blasdel BG, Kutter EM. Phage Treatment of human infections. Bacteriophage. 2011;1:66–85. doi: 10.4161/bact.1.2.15845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bernstein D, Fischetti VA. Method for exposing group a streptococcal antigens and an improved diagnostic test for the identification of group a streptococci. 1997. [Google Scholar]
  4. Briersa Y, Walmagha M, Van Puyenbroecka V, Cornelissena A, Cenensb W, Aertsenb A, Oliveirac H, Azeredoc J, Verweend G, Pirnayd JP, Miller S, Volckaerta G, Lavignea R. Engineered Endolysin-Based “Artilysins” To Combat Multidrug-Resistant Gram-Negative Pathogens. MBio. 2014;5:e01379–14. doi: 10.1128/mBio.01379-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bruynoghe R, Maisin J. Essais de thérapeutique au moyen du bactériophage du Staphylocoque. Compt Rend Soc Biol. 1921;85:1120–1121. [Google Scholar]
  6. Cutter CN, Dorsa WJ, Siragusa GR. A rapid microbial ATP bioluminescence assay for meat carcasses. Dairy, Food & Environ. San. 1996;16:726–736. [Google Scholar]
  7. d’Herelle FH. Sur un microbe invisible antagoniste des bacilles dysenteriques. C R Acad Sci Gen. 1917;165:373–375. [Google Scholar]
  8. d’Hérelle F. Bacteriophagy and recovery from infectious disease. Can Med Assoc J. 1931;24:619–628. [PMC free article] [PubMed] [Google Scholar]
  9. Filatova L, Levashov AV, Dmitrieva NF, Eshchina AS, Klyachko NL. Encapsulation of enzyme lysing group A streptococci to improve its stability. In: Marison I, Poncelet D, editors. Proc XVIth Int Workshop on Bioencapsulation. 2008. pp. 1–4. [Google Scholar]
  10. Fischetti VA. Bacteriophage lytic enzymes: novel anti-infectives. Trends Microbiol. 2005;13:491–496. doi: 10.1016/j.tim.2005.08.007. [DOI] [PubMed] [Google Scholar]
  11. Fischetti VA, Gotschlich EC, Bernheimer AW. Purification and Physical Properties of Group C Streptococcal Phage Associated Lysin. J Exp Med. 1971;133:1105–1117. doi: 10.1084/jem.133.5.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fischetti VA, Loomis L. Prophylactic and therapeutic treatment of group A streptococcal infection. 1999. [Google Scholar]
  13. Florin P. Bacterial Contamination in a Field Hospital. 2006. [Google Scholar]
  14. Hasan JAK, Garg S, Loomis L, Miller D, Colwell RR. Abstr 97th General Meeting of Am. Soc. Microbiol. 1997. A rapid surface-monitoring method for bacteria employing ATP bioluminescence. [Google Scholar]
  15. Hankin ME. L’action bactéricide des eaux de la Jumna et du Gange sur le vibrion du choléra. Ann Inst Pasteur (Paris) 1896;10:511–523. [Google Scholar]
  16. Harper DR, Kutter E. Bacteriophage: therapeutic use. Encyclopedia of Life Sciences. Chichester, UK: John Wiley & Sons, Ltd.; 2008. pp. 1–7. [Google Scholar]
  17. Ho K. Bacteriophage therapy for bacterial infections. Rekindling a memory from the pre-antibiotics era. Perspect Biol Med. 2001;44:1–16. doi: 10.1353/pbm.2001.0006. [DOI] [PubMed] [Google Scholar]
  18. Hoopes JT, Stark CJ, Kim HA, Sussman DJ, Donovan DM, Nelson DC. Use of a bacteriophage lysin, PlyC, as an enzyme disinfectant against Streptococcus equi. Appl Environ Microbiol. 2009;75:1388–1394. doi: 10.1128/AEM.02195-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Krause RM.1958. Studies on the Bacteriophages of Hemolytic Streptococci. J Exp Med, 108: 803–821. [DOI] [PMC free article] [PubMed]
  20. Klyachko NL, Dmitrieva NF, Eshchina AS, Ignatenko OV, Filatova LY, Rainina EI, Kazarov AK, Levashov AV. Bacteriophage enzyme for the prevention and treatment of bacterial infections: stability and stabilization of the enzyme lysing Streptococcus pyogenes cells. Russ J Bioorganic Chem. 2008;34:375–379. doi: 10.1134/S1068162008030217. [DOI] [PubMed] [Google Scholar]
  21. Maxted WR. The Active Agent in Nascent Phage Lysis of Streptococci. J Gen Micro. 1957;16:585–595. doi: 10.1099/00221287-16-3-584. [DOI] [PubMed] [Google Scholar]
  22. Nelson D, Loomis L, Fischetti VA. Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using bacteriophage lytic enzyme. Proc Natl Acad Sci U S A. 2001;98:4107–4112. doi: 10.1073/pnas.061038398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Roach DR, Khatibi PA, Bischoff KM, Hughes SR, Donovan DM. Bacteriophage-encoded lytic enzymes control growth of contaminating Lactobacillus found in fuel ethanol fermentations. Biotechnol Biofuels. 2013;6:20. doi: 10.1186/1754-6834-6-20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Schmelcher M, Powella A, Beckera S, Campb M, Donovan D. Chimeric phage lysins act synergistically with lysostaphin to kill mastitis — causing Staphylococcus aureus in murine mammary glands. Appl Environ Microbiol. 2012;78:2297–2305. doi: 10.1128/AEM.07050-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schuch R, Nelso D, Fischetti V. A bacteriolytic agent that detects and kills Bacillus anthracis. Nature. 2002;418:884–889. doi: 10.1038/nature01026. [DOI] [PubMed] [Google Scholar]
  26. Siragusa GR, Cutter CN, Dorsa WJ, Koohmaraie M. Use of a rapid microbial ATP bio- luminescence assay to detect contamination on beef and pork carcasses. J Food Prot. 1995;58:770–775. doi: 10.4315/0362-028X-58.7.770. [DOI] [PubMed] [Google Scholar]
  27. Siragusa GR, Dorsa WJ, Cutter CN, Perino LJ, Koohmaraie M. Use of a newly developed rapid microbial ATP bioluminescence assay to detect microbial contamination on poultry carcasses. J Biolumin Chemilumin. 1996;11:297–301. doi: 10.1002/(SICI)1099-1271(199611)11:6<297::AID-BIO422>3.0.CO;2-C. [DOI] [PubMed] [Google Scholar]
  28. Stopa PJ, Tieman D, Coon PA, Milton MM, Paterno D. Detection of biological aerosols by luminescence techniques. Field Anal Chem Technol. 1999;3:283–290. doi: 10.1002/(SICI)1520-6521(1999)3:4/5<283::AID-FACT7>3.0.CO;2-9. [DOI] [Google Scholar]
  29. Sulakvelidze A, Barrow P. Bacteriophages: Biology and Applications. Kutter E, Sulakvelidze. Boca Raton: CRC Press; 2005. Phage therapy in animals and agribusiness; pp. 335–380. [Google Scholar]
  30. Summers WC. Bacteriophage therapy. Annu Rev Microbiol. 2001;55:437–451. doi: 10.1146/annurev.micro.55.1.437. [DOI] [PubMed] [Google Scholar]
  31. Trudil D. Use of phage associated lytic enzymes for rapid detection of bacterial contaminants (priority date 1999) 2002. [Google Scholar]
  32. Trudil D, Rainina E. Proc 5TH SISPAT, Singapore. 2006. Use of Lytic Enzymes for Microbiological Decontamination of Sensitive Facilities. [Google Scholar]
  33. Twort FW. An investigation on the nature of ultramicroscopic viruses. Lancet. 1915;186:1241–1246. doi: 10.1016/S0140-6736(01)20383-3. [DOI] [Google Scholar]
  34. Yang H, Zhang Y, Yu J, Huang Y, Zhang XE, Wei H. Novel chimeric lysin with high-level antimicrobial activity against methicillin-resistant Staphylococcus aureus in vitro and in vivo. Antimicrob Agents Ch. 2014;58:536–542. doi: 10.1128/AAC.01793-13. [DOI] [PMC free article] [PubMed] [Google Scholar]

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