The phage K lytic enzyme LysK and lysostaphin act synergistically to kill MRSA

FEMS Microbiology Letters

Volumn 287, Issue 2, 2008, Pages 185-191

  Becker, Stephen C ^a   Foster Frey, Juli ^a   Donovan, David M ^a  

^a AGRICULTURAL RESEARCH SERVICE   (United States)

Author keywords

ALE 1; LAS; Lysostaphin; LytM; Minimal inhibitory concentration; Turbidity assay

Indexed keywords

BACTERIAL ENZYME; LYSK PROTEIN; LYSOSTAPHIN; RECOMBINANT PROTEIN; SODIUM CHLORIDE; UNCLASSIFIED DRUG;

AMINO TERMINAL SEQUENCE; ARTICLE; BACTERIOLYSIS; CARBOXY TERMINAL SEQUENCE; CHEMICAL REACTION; CONTROLLED STUDY; DRUG POTENTIATION; METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; NONHUMAN; NUCLEOTIDE SEQUENCE; PH; PRIORITY JOURNAL; PROTEIN FUNCTION;

ANTI-BACTERIAL AGENTS; DRUG SYNERGISM; ENDOPEPTIDASES; ESCHERICHIA COLI; HUMANS; LYSOSTAPHIN; METHICILLIN RESISTANCE; MICROBIAL SENSITIVITY TESTS; RECOMBINANT FUSION PROTEINS; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCUS PHAGES; VIRAL PROTEINS;

METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCUS; STAPHYLOCOCCUS AUREUS; STAPHYLOCOCCUS SIMULANS;

EID: 51349140468     PISSN: 03781097     EISSN: 15746968     Source Type: Journal    
DOI: 10.1111/j.1574-6968.2008.01308.x     Document Type: Article

References (30)

1. Bhakta M, Arora S Bal M (2003) Intraspecies transfer of a chloramphenicol-resistance plasmid of staphylococcal origin. Indian J Med Res 117 : 146 151.
2. Bochtler M, Odintsov SG, Marcyjaniak M Sabala I (2004) Similar active sites in lysostaphins and d-Ala-d-Ala metallopeptidases. Protein Sci 13 : 854 861.
3. Browder HP, Zygmunt WA, Young JR Tabormina PA (1965) Lysostaphin: enzymatic mode of action. Biochem Biophys Res Commun 19 : 383 389.
4. Cheng Q, Nelson D, Zhu S Fischetti VA (2005) Removal of group B streptococci colonizing the vagina and oropharynx of mice with a bacteriophage lytic enzyme. Antimicrob Agents Chemother 49 : 111 117.
5. Cisani G, Varaldo PE, Grazi G Soro O (1982) High-level potentiation of lysostaphin anti-staphylococcal activity by lysozyme. Antimicrob Agents Chemother 21 : 531 535.
6. Dajcs JJ, Hume EB, Moreau JM, Caballero AR, Cannon BM O'Callaghan RJ (2000) Lysostaphin treatment of methicillin-resistant Staphylococcus aureus keratitis in the rabbit(1). Am J Ophthalmol 130 : 544.
7. Djurkovic S, Loeffler JM Fischetti VA (2005) 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 49 : 1225 1228.
8. Donovan DM (2007) Bacteriophage and peptidoglycan degrading enzymes with antimicrobial applications. Recent Patents Biotechnol 1 : 113 122.
9. Donovan DM, Dong S, Garrett W, Rousseau GM, Moineau S Pritchard DG (2006) Peptidoglycan hydrolase fusions maintain their parental specificities. Appl Environ Microbiol 72 : 2988 2996.
10. Entenza JM, Loeffler JM, Grandgirard D, Fischetti VA Moreillon P (2005) Therapeutic effects of bacteriophage Cpl-1 lysin against Streptococcus pneumoniae endocarditis in rats. Antimicrob Agents Chemother 49 : 4789 4792.
11. Fischetti VA (2003) Novel method to control pathogenic bacteria on human mucous membranes. Ann N Y Acad Sci 987 : 207 214.
12. Fischetti VA (2005) Bacteriophage lytic enzymes: novel anti-infectives. Trends Microbiol 13 : 491 496.
13. Graham S Coote PJ (2007) Potent, synergistic inhibition of Staphylococcus aureus upon exposure to a combination of the endopeptidase lysostaphin and the cationic peptide ranalexin. J Antimicrob Chemother 59 : 759 762.
14. Hall MJ, Middleton RF Westmacott D (1983) The fractional inhibitory concentration (FIC) index as a measure of synergy. J Antimicrob Chemother 11 : 427 433.
15. Jado I, Lopez R, Garcia E, Fenoll A, Casal J Garcia P (2003) Phage lytic enzymes as therapy for antibiotic-resistant Streptococcus pneumoniae infection in a murine sepsis model. J Antimicrob Chemother 52 : 967 973.
16. Jones RN, Barry AL, Gavan TL Washington JA II. (1985) Susceptibility tests: microdilution and macrodilution broth procedures. Manual of Clinical Microbiology (Balows A, Hausler JWJ Shadomy HJ, eds), pp. 972 977. American Society for Microbiology, Washington, DC.
17. Kiri N, Archer G Climo MW (2002) Combinations of lysostaphin with beta-lactams are synergistic against oxacillin-resistant Staphylococcus epidermidis. Antimicrob Agents Chemother 46 : 2017 2020.
18. Kokai-Kum JF (2003) Methods and formulations for eradicating or allevating staphylococcal nasal colonization using lysostaphin. European Patent EP1463408. Available at
19. Kusuma CM Kokai-Kun JF (2005) Comparison of four methods for determining lysostaphin susceptibility of various strains of Staphylococcus aureus. Antimicrob Agents Chemother 49 : 3256 3263.
20. Loeffler JM Fischetti VA (2003b) Synergistic lethal effect of a combination of phage lytic enzymes with different activities on penicillin-sensitive and -resistant Streptococcus pneumoniae strains. Antimicrob Agents Chemother 47 : 375 377.
21. Loeffler JM, Djurkovic S Fischetti VA (2003a) Phage lytic enzyme Cpl-1 as a novel antimicrobial for pneumococcal bacteremia. Infect Immun 71 : 6199 6204.
22. Loessner MJ (2005) Bacteriophage endolysins - current state of research and applications. Curr Opin Microbiol 8 : 480 487.
23. Nelson D, Loomis L Fischetti VA (2001) Prevention and elimination of upper respiratory colonization of mice by group A streptococci by using a bacteriophage lytic enzyme. Proc Natl Acad Sci USA 98 : 4107 4112.
24. O'Flaherty S, Coffey A, Meaney W, Fitzgerald GF Ross RP (2005) The recombinant phage lysin LysK has a broad spectrum of lytic activity against clinically relevant staphylococci, including methicillin-resistant Staphylococcus aureus. J Bacteriol 187 : 7161 7164.
25. Patron RL, Climo MW, Goldstein BP Archer GL (1999) Lysostaphin treatment of experimental aortic valve endocarditis caused by a Staphylococcus aureus isolate with reduced susceptibility to vancomycin. Antimicrob Agents Chemother 43 : 1754 1755.
26. Polak J, Della LP Blackburn P (1993) In vitro activity of recombinant lysostaphin-antibiotic combinations toward methicillin-resistant Staphylococcus aureus. Diagn Microbiol Infect Dis 17 : 265 270.
27. Schindler CA Schuhardt VT (1965) Purification and properties of lysostaphin - a lytic agent for Staphylococcus aureus. Biochim Biophys Acta 97 : 242 250.
28. Schuch R, Nelson D Fischetti VA (2002) A bacteriolytic agent that detects and kills Bacillus anthracis. Nature 418 : 884 889.
29. Walencka E, Sadowska B, Rozalska S, Hryniewicz W Rozalska B (2005) Lysostaphin as a potential therapeutic agent for staphylococcal biofilm eradication. Pol J Microbiol 54 : 191 200.
30. Wu JA, Kusuma C, Mond JJ Kokai-Kun JF (2003) Lysostaphin disrupts Staphylococcus aureus and Staphylococcus epidermidis biofilms on artificial surfaces. Antimicrob Agents Chemother 47 : 3407 3414.