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Modular Engineering of Lysostaphin with Significantly Improved Stability and Bioavailability for Treating MRSA
Jingwei Liu1,2, Yumei Li1, Shuang Wang2,3
1Department of Pediatric Intensive Care Unit, Children's Medical Center, The First Hospital of Jilin University, Changchun 130021, China.
ACS Applied Materials & Interfaces
|January 15, 2025
Summary
Engineered lysostaphin combats antibiotic-resistant bacteria like MRSA. This nanoassembly strategy improves stability and bioavailability, offering a promising platform for clinical applications against persistent infections.
Area of Science:
- Biochemistry
- Microbiology
- Materials Science
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) causes difficult-to-treat pneumonia due to antibiotic resistance and intracellular persistence.
- Lysostaphin, a bacteriolytic enzyme, degrades bacterial cell walls but suffers from poor stability and bioavailability.
Purpose of the Study:
- To engineer native lysostaphin using a modular assembly strategy to overcome its limitations.
- To enhance the antibacterial activity, bioavailability, and shelf stability of lysostaphin for combating MRSA infections.
Main Methods:
- A modular assembly strategy was employed, fusing native lysostaphin with a lysine-rich polypeptide to create a nanoassembled enzyme.
- The engineered lysostaphin's membrane-penetration capability, intracellular antibacterial activity, half-life, and shelf stability were evaluated.
Main Results:
- The engineered lysostaphin demonstrated a 12-fold increase in intracellular antibacterial activity compared to wild-type lysostaphin.
- The nanoassembled lysostaphin exhibited a 13-fold longer half-life and retained over 99.9% activity after 12 weeks at room temperature.
- The modular assembly strategy significantly improved lysostaphin's overall performance and shelf stability.
Conclusions:
- The modular assembly strategy successfully enhances lysostaphin's efficacy and stability for combating MRSA.
- Engineered lysostaphin shows significant promise as a platform technology for clinical applications against multidrug-resistant bacterial infections.
