Characterization and bioinformatic analysis of a new chimeric endolysin against MRSA with great stability

• Published in: AMB Express 2024-12, Vol.14 (1), p.143-12, Article 143
• Main Authors: Momen, Sanaz, Soleimani, Neda, Azizmohseni, Farzaneh, Ahmadbeigi, Yasaman, Borhani, Seddigheh, Amini-Bayat, Zahra
• Format: Article
• Language: English
• Subjects: Antibiotic resistance; Antibiotics; Bactericidal activity; Biofilm; Biofilms; Biomedical and Life Sciences; Biotechnology; Bond number; Chemical bonds; Chimeric endolysin; Drug resistance; Dynamic stability; Hydrogen bonds; Infectious diseases; Life Sciences; Low concentrations; Lysostaphin; Methicillin; Microbial Genetics and Genomics; Microbiology; Molecular dynamics; MRSA; Original Article; Peptidoglycans; Staphylococcus aureus; Staphylococcus infections; Thermal stability
• ISSN: 2191-0855; 2191-0855
• DOI: 10.1186/s13568-024-01812-2

Antibiotics become less effective in treating infectious diseases as resistance increases. S taphylococcus aureus is a global problem due to its ability to form biofilms and resistance mechanisms. Phage endolysin is one of the most promising methods for combating antibiotic resistance. ZAM-MSC chimeric endolysin has three domains derived from SAL1 and lysostaphin, which target the peptide bridge of peptidoglycan. In this study purified ZAM-MSC (with yield of 30 mg/lit) had bactericidal activity against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) at low concentrations (2.38 μg/ml and 1.88 μg/ml, respectively). The antibacterial spectrum revealed that ZAM-MSC was active against diverse Staphylococci . it has maintained 100% stability after 24 h incubation in pH 5 to 10 against S. aureus , as well as demonstrated significant thermostability and maintained nearly its full activity at different temperatures (4–42 °C) up to 1 day of incubation. The anti-biofilm activity of various concentrations of ZAM-MSC against MSSA and MRSA biofilms was not dose-dependent, and antibiofilm activity was observed even at low concentrations (14 μg/ml). Further, the molecular dynamics simulations demonstrated that the ZAM-MSC chimer and its parent proteins remained dynamically stable, showing similar flexibility despite the size and hydrogen bond number differences. In conclusion, the study reveals that chimeric ZAM-MSC is a distinctive enzyme with exceptional biochemical properties and rapid lytic activity against Staphylococci .