Iranian Journal of Microbiology 2017. 9(4):208-212.

In vitro activity of recombinant lysostaphin in combination with linezolid, vancomycin and oxacillin against methicillin-resistant Staphylococcus aureus
Nagalakshmi Narasimhaswamy, Indira Bairy, Gautham Shenoy, Laxminarayana Bairy



Background and Objectives: The antimicrobial combination with synergistic mechanism is recommended to provide broad-spectrum coverage, and prevent the emergence of resistant mutants. In the present study, the synergistic activity of lysostaphin with linezolid, oxacillin and vancomycin, against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates was determined.

Materials and Methods: Seventy-three MRSA isolates collected from clinical specimens were tested, for in vitro synergistic activity of lysostaphin with linezolid, vancomycin and oxacillin, by checkerboard assay. 

Results: Lysostaphin showed synergistic activity with linezolid and oxacillin, against all MRSA isolates, tested in the present study. Whereas, only 19.1% of the isolates showed synergistic activity with vancomycin and remaining 80.9% of the MRSA isolates showed additive activity.

Conclusion: Lysostaphin causes rapid lysis of S. aureus. Combination therapies that include linezolid and lysostaphin could be used in life-threatening infections, such as endocarditis to increase the early in vivo activity of the antibiotics, and to prevent the emergence of linezolid resistant mutants. Further, in vivo studies are warranted to confirm our results.


Lysostaphin, Methicillin resistant Staphylococcus aureus (MRSA), Synergistic activity

Full Text:



Lowy FD. Staphylococcus aureus infections. N Engl J Med 1998;339:520-532.

Ryu S, Song PI, Seo CH, Cheong H, Park Y. Colonization and infection of the skin by S. aureus: immune system evasion and the response to cationic antimicrobial peptides. Int J Mol Sci 2014;15:8753-8772.

Jevons MP. “Celbenin”-resistant Staphylococci. Brit Med J 1961;1(5219):124-125.

Grundmann H, Aires-de-Sousa M, Boyce J, Tiemersma E. Emergence and resurgence of meticillin-resistant Staphylococcus aureus as a public-health threat. Lancet 2006;368(9538):874-885.

Gründling A, Schneewind O. Cross-linked peptidoglycan mediates lysostaphin binding to the cell wall envelope of Staphylococcus aureus. J Bacteriol 2006;188:2463-2472.

Browder HP, Zygmunt WA, Young JR, Tavormina PA. Lysostaphin: enzymatic mode of action. Biochem Biophys Res Commun 1965;19:383-389.

Kumar A, Khan IA, Sharma PR, Sumathy K, Krishna ME. Evaluation of activity of recombinant lysostaphin against isolates of meticillin-resistant Staphylococcus aureus from Indian hospitals. J Med Microbiol 2014;63:763-766.

Kumar JK. Lysostaphin: an antistaphylococcal agent. Appl Microbiol Biotechnol 2008;80:555-561.

Kokai-Kun J (2012). Lysostaphin: a silver bullet for staph. In: Tegos A. ME, ed, Antimicrobial Drug Discovery. CABI publishing, 1st ed. Oxfordshire, Wallingford, UK, pp. 147-165.

Grohs P, Kitzis MD, Gutmann L. In vitro bactericidal activities of linezolid in combination with vancomycin, gentamicin, ciprofloxacin, fusidic acid, and rifampin against Staphylococcus aureus. Antimicrob Agents Chemother 2003;47:418-420.

Grif K, Dierich MP, Pfaller K, Miglioli PA, Allerberger F. In vitro activity of fosfomycin in combination with various antistaphylococcal substances. J Antimicrob Chemother 2001;48:209-217.

CLSI (2010). Performance Standards for Antimicrobial Susceptibility Testing: Twentieth Informational Supplement. M100-S20. PA, USA.

Garcia LS (2010). Clinical Microbiology Procedures Handbook. 3rd ed. American Society of Microbiology Press. Washington DC.

Jacqueline C, Caillon J, Le Mabecque V, Miegeville AF, Donnio PY, Bugnon D, et al. In vitro activity of linezolid alone and in combination with gentamicin, vancomycin or rifampicin against methicillin-resistant Staphylococcus aureus by time-kill curve methods. J Antimicrob Chemother 2003;51:857-864.

Climo MW, Ehlert K, Archer GL. Mechanism and suppression of lysostaphin resistance in oxacillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2001;45:1431-1437.

Kusuma C, Jadanova A, Chanturiya T, Kokai-Kun JF. Lysostaphin-resistant variants of Staphylococcus aureus demonstrate reduced fitness in vitro and in vivo. Antimicrob Agents Chemother 2007;51:475-482.

Polak J, Latta PD, Blackburn P. In vitro activity of recombinant lysostaphin-antibiotic combinations toward methicillin-resistant Staphylococcus aureus. Diagn Microbiol Infect Dis 1993;17:265-270.

Desbois AP, Coote PJ. Bactericidal synergy of lysostaphin in combination with antimicrobial peptides. Eur J Clin Microbiol Infect Dis 2011;30:1015-1021.

Kiri N, Archer G, Climo MW. Combinations of lysostaphin with β-lactams are synergistic against oxacillin-resistant Staphylococcus epidermidis. Antimicrob Agents Chemother 2002;46:2017-2020.

Climo MW, Patron RL, Goldstein BP, Archer GL. Lysostaphin treatment of experimental methicillin-resistant Staphylococcus aureus aortic valve endocarditis. Antimicrob Agents Chemother 1998;42:1355-1360.

Kokai-Kun JF, Chanturiya T, Mond JJ. Lysostaphin as a treatment for systemic Staphylococcus aureus infection in a mouse model. J Antimicrob Chemother 2007;60:1051-1059.

Clara Sei TC, James J. Mond, John F. Kokai-Kun. Lysostaphin reduces the production of inflammatory cytokines in Staphylococcus aureus challenged mice, and prevents systemic shock. Open Antimicrobl Agents J 2011;3:6-11.

Ip WK, Sokolovska A, Charriere GM, Boyer L, Dejardin S, Cappillino MP, et al. Phagocytosis and phagosome acidification are required for pathogen processing and MyD88-dependent responses to Staphylococcus aureus. J Immunol 2010;184:7071-7081.


  • There are currently no refbacks.

Creative Commons Attribution-NonCommercial 3.0

This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.