Bacteriophage Endolysins: a Novel Anti-infective to Control Gram-positive Pathogens

Overview

Journal Int J Med Microbiol

Specialty Microbiology

Date 2010 May 11

PMID 20452280

Citations 197

Authors

Vincent A Fischetti

Affiliations

Soon will be listed here.

Abstract

Endolysins (or lysins) are highly evolved enzymes produced by bacteriophage (phage for short) to digest the bacterial cell wall for phage progeny release. In Gram-positive bacteria, small quantities of purified recombinant lysin added externally results in immediate lysis causing log-fold death of the target bacterium. Lysins have been used successfully in a variety of animal models to control pathogenic antibiotic-resistant bacteria found on mucosal surfaces and infected tissues. Their specificity for the pathogen without disturbing the normal flora, the low chance of bacterial resistance, and their ability to kill colonizing pathogens on mucosal surfaces, a capacity previously unavailable, make them ideal anti-infectives in an age of mounting resistance. Here we review the current literature showing the effectiveness of these enzymes in controlling a variety of infections.

Citing Articles

Phage-derived proteins: Advancing food safety through biocontrol and detection of foodborne pathogens.

Choi D, Ryu S, Kong M Compr Rev Food Sci Food Saf. 2025; 24(2):e70124.

PMID: 39898971 PMC: 11891642. DOI: 10.1111/1541-4337.70124.

Novel Anti-Microbial/Anti-Inflammatory Combination Improves Clinical Outcome of Bacillus cereus Endophthalmitis.

Mursalin M, Coburn P, Longoria-Gonzalez L, Astley R, Fischetti V, Callegan M Invest Ophthalmol Vis Sci. 2025; 66(1):39.

PMID: 39813055 PMC: 11741065. DOI: 10.1167/iovs.66.1.39.

Structural and functional analysis reveals the catalytic mechanism and substrate binding mode of the broad-spectrum endolysin Ply2741.

Wang S, Li X, Ma J, Duan X, Wang H, Wang L Virulence. 2025; 16(1):2449025.

PMID: 39810299 PMC: 11740692. DOI: 10.1080/21505594.2024.2449025.

Recombinant design of the enzymatically active domain of phage Enc34 endolysin to improve its activity against Gram-negative bacteria.

Kazaka T, Zrelovs N, Akopjana I, Bogans J, Jansons J, Dislers A FEMS Microbiol Lett. 2024; 371.

PMID: 39673269 PMC: 11657235. DOI: 10.1093/femsle/fnae103.

A novel chimeric endolysin Cly2v shows potential in treating streptococci-induced bovine mastitis and systemic infections.

Wang S, Li X, Ji J, Li X, Zhu H, Duan X Front Microbiol. 2024; 15:1482189.

PMID: 39493846 PMC: 11527626. DOI: 10.3389/fmicb.2024.1482189.

References

OFlaherty S, Coffey A, Edwards R, Meaney W, Fitzgerald G, Ross R . Genome of staphylococcal phage K: a new lineage of Myoviridae infecting gram-positive bacteria with a low G+C content. J Bacteriol. 2004; 186(9):2862-71. PMC: 387793. DOI: 10.1128/JB.186.9.2862-2871.2004. View

Grandgirard D, Loeffler J, Fischetti V, Leib S . Phage lytic enzyme Cpl-1 for antibacterial therapy in experimental pneumococcal meningitis. J Infect Dis. 2008; 197(11):1519-22. DOI: 10.1086/587942. View

Young I, Wang I, Roof W . Phages will out: strategies of host cell lysis. Trends Microbiol. 2000; 8(3):120-8. DOI: 10.1016/s0966-842x(00)01705-4. View

Matsuzaki S, Rashel M, Uchiyama J, Sakurai S, Ujihara T, Kuroda M . Bacteriophage therapy: a revitalized therapy against bacterial infectious diseases. J Infect Chemother. 2005; 11(5):211-9. DOI: 10.1007/s10156-005-0408-9. View

Djurkovic S, Loeffler J, Fischetti V . Synergistic killing of Streptococcus pneumoniae with the bacteriophage lytic enzyme Cpl-1 and penicillin or gentamicin depends on the level of penicillin resistance. Antimicrob Agents Chemother. 2005; 49(3):1225-8. PMC: 549239. DOI: 10.1128/AAC.49.3.1225-1228.2005. View

Garcia E, Garcia J, Garcia P, Arraras A, Sanchez-Puelles J, Lopez R . Molecular evolution of lytic enzymes of Streptococcus pneumoniae and its bacteriophages. Proc Natl Acad Sci U S A. 1988; 85(3):914-8. PMC: 279667. DOI: 10.1073/pnas.85.3.914. View

Brundage J, Shanks G . What really happened during the 1918 influenza pandemic? The importance of bacterial secondary infections. J Infect Dis. 2007; 196(11):1717-8. DOI: 10.1086/522355. View

Coello R, Jimenez J, Garcia M, Arroyo P, Minguez D, Fernandez C . Prospective study of infection, colonization and carriage of methicillin-resistant Staphylococcus aureus in an outbreak affecting 990 patients. Eur J Clin Microbiol Infect Dis. 1994; 13(1):74-81. DOI: 10.1007/BF02026130. View

Pritchard D, Dong S, Kirk M, Cartee R, Baker J . LambdaSa1 and LambdaSa2 prophage lysins of Streptococcus agalactiae. Appl Environ Microbiol. 2007; 73(22):7150-4. PMC: 2168211. DOI: 10.1128/AEM.01783-07. View

10.

Garcia P, Garcia J, Garcia E, Sanchez-Puelles J, Lopez R . Modular organization of the lytic enzymes of Streptococcus pneumoniae and its bacteriophages. Gene. 1990; 86(1):81-8. DOI: 10.1016/0378-1119(90)90116-9. View

11.

Lopez R, Garcia J, Garcia E, Ronda C, Garcia P . Structural analysis and biological significance of the cell wall lytic enzymes of Streptococcus pneumoniae and its bacteriophage. FEMS Microbiol Lett. 1992; 100(1-3):439-47. DOI: 10.1111/j.1574-6968.1992.tb14074.x. View

12.

Loessner M . Bacteriophage endolysins--current state of research and applications. Curr Opin Microbiol. 2005; 8(4):480-7. DOI: 10.1016/j.mib.2005.06.002. View

13.

Jado I, Lopez R, Garcia E, Fenoll A, Casal J, Garcia P . Phage lytic enzymes as therapy for antibiotic-resistant Streptococcus pneumoniae infection in a murine sepsis model. J Antimicrob Chemother. 2003; 52(6):967-73. DOI: 10.1093/jac/dkg485. View

14.

Yoong P, Schuch R, Nelson D, Fischetti V . Identification of a broadly active phage lytic enzyme with lethal activity against antibiotic-resistant Enterococcus faecalis and Enterococcus faecium. J Bacteriol. 2004; 186(14):4808-12. PMC: 438584. DOI: 10.1128/JB.186.14.4808-4812.2004. View

15.

Hudson I . The efficacy of intranasal mupirocin in the prevention of staphylococcal infections: a review of recent experience. J Hosp Infect. 1994; 27(2):81-98. DOI: 10.1016/0195-6701(94)90001-9. View

16.

Cheng Q, Nelson D, Zhu S, Fischetti V . Removal of group B streptococci colonizing the vagina and oropharynx of mice with a bacteriophage lytic enzyme. Antimicrob Agents Chemother. 2004; 49(1):111-7. PMC: 538902. DOI: 10.1128/AAC.49.1.111-117.2005. View

17.

OFlaherty S, Coffey A, Meaney W, Fitzgerald G, Ross R . The recombinant phage lysin LysK has a broad spectrum of lytic activity against clinically relevant staphylococci, including methicillin-resistant Staphylococcus aureus. J Bacteriol. 2005; 187(20):7161-4. PMC: 1251611. DOI: 10.1128/JB.187.20.7161-7164.2005. View

18.

Tuomanen E, Liu H, Hengstler B, Zak O, Tomasz A . The induction of meningeal inflammation by components of the pneumococcal cell wall. J Infect Dis. 1985; 151(5):859-68. DOI: 10.1093/infdis/151.5.859. View

19.

Rashel M, Uchiyama J, Ujihara T, Uehara Y, Kuramoto S, Sugihara S . Efficient elimination of multidrug-resistant Staphylococcus aureus by cloned lysin derived from bacteriophage phi MR11. J Infect Dis. 2007; 196(8):1237-47. DOI: 10.1086/521305. View

20.

Wang I, Smith D, Young R . Holins: the protein clocks of bacteriophage infections. Annu Rev Microbiol. 2000; 54:799-825. DOI: 10.1146/annurev.micro.54.1.799. View