Sanaz Momen: Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Neda Soleimani: Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Farzaneh Azizmohseni: Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST), Tehran, Iran.
Yasaman Ahmadbeigi: Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
Zahra Amini-Bayat: Department of Biotechnology, Iranian Research Organization for Science and Technology (IROST), Tehran, Iran. Amini-bayat@irost.org. ORCID
Antibiotics become less effective in treating infectious diseases as resistance increases. Staphylococcus 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 ��g/ml and 1.88 ��g/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 ��g/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.
