Lysostaphin is a zinc-containing metalloprotease with antibacterial activity. Lysostaphin specifically hydrolyzes the pentaglycine peptide bond bridges in the bacterial cell wall peptidoglycan to lyse staphylococcal cell walls, while also clearing persistent infections by disrupting biofilm structures. Lysostaphin can be used in research related to Staphylococcus aureus infections (including MRSA) and biofilm-associated infections (such as orthopedic implant infections and pneumonia)[1-4].
In vitro, KKU-213A and KKU-213B cholangiocarcinoma cell lines were treated with Lysostaphin (12.5μg/mL) for 72 hours. Lysostaphin significantly inhibited cell growth, induced apoptosis, and upregulated the expression of pro-apoptotic genes BAX, caspase-3, caspase-8, and caspase-9[5]. BALB/3T3 cells that had taken up Staphylococcus aureus A191, A151, and Cowan I were treated with Lysostaphin (1.25μg/ml) for 0 to 21 hours. Lysostaphin cleared extracellular bacteria, allowing intracellular Staphylococcus aureus to escape endosomes, proliferate, and induce apoptosis[6].
In vivo, 2-day-old newborn FVB mice subcutaneously infected with MRSA USA300 strain were intraperitoneally injected with Lysostaphin (10mg/kg or 15mg/kg; total of 4 doses) at 0.5, 6, 24, and 30 hours post-infection. Lysostaphin significantly improved the survival rate of infected mice, enhanced growth rate, and reduced colony counts in quantitative blood cultures[7]. Jugular vein catheterized mice infected with Staphylococcus aureus (including MRSA) were administered Lysostaphin (15mg/kg) combined with nafcillin (50mg/kg) through the catheter three times daily for 4 days. Lysostaphin combined with nafcillin eradicated established Staphylococcus aureus biofilms from implanted catheters and eliminated infections in the heart and liver[8].
References:
[1] Koening MG. Lysostaphin. J Infect Dis. 1969 Jan;119(1):101-2.
[2] Kumar JK. Lysostaphin: an antistaphylococcal agent. Appl Microbiol Biotechnol. 2008 Sep;80(4):555-61.
[3] Jayakumar J, Kumar VA, Biswas L, et al. Therapeutic applications of lysostaphin against Staphylococcus aureus. J Appl Microbiol. 2021 Sep;131(3):1072-1082.
[4] Zha J, Li J, Su Z, et al. Lysostaphin: Engineering and Potentiation toward Better Applications. J Agric Food Chem. 2022 Sep 21;70(37):11441-11457.
[5] Kerdkumthong K, Chanket W, Runsaeng P, et al. Two Recombinant Bacteriocins, Rhamnosin and Lysostaphin, Show Synergistic Anticancer Activity Against Gemcitabine-Resistant Cholangiocarcinoma Cell Lines. Probiotics Antimicrob Proteins. 2024 Jun;16(3):713-725.
[6] Murai M, Sakurada J, Seki K, et al. Apoptosis observed in BALB/3T3 cells having ingested Staphylococcus aureus. Microbiol Immunol. 1999;43(7):653-61.
[7] Placencia FX, Kong L, Weisman LE. Treatment of methicillin-resistant Staphylococcus aureus in neonatal mice: lysostaphin versus vancomycin. Pediatr Res. 2009 Apr;65(4):420-4.
[8] Kokai-Kun JF, Chanturiya T, Mond JJ. Lysostaphin eradicates established Staphylococcus aureus biofilms in jugular vein catheterized mice. J Antimicrob Chemother. 2009 Jul;64(1):94-100.