Lysozyme

Introduction to Lysozyme

Lysozyme, also known as muramidase or N-acetylmuramide glycanhydrolase (EC 3.2.1.17), is a glycoside hydrolase enzyme central to the innate immune system. It catalyzes the hydrolysis of (1→4)-β-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in bacterial peptidoglycan, a structural component of gram-positive bacterial cell walls . This enzymatic activity compromises bacterial integrity, leading to cell lysis and death. Lysozyme is abundant in human secretions (tears, saliva, mucus, breast milk) and tissues, with additional sources including avian egg whites and transgenic organisms engineered to produce human lysozyme .

Mechanism of Action

Lysozyme targets peptidoglycan, a polysaccharide backbone critical for bacterial cell wall rigidity. By cleaving β-(1,4)-glycosidic bonds, it destabilizes the bacterial cell wall, causing osmotic pressure-driven lysis . This mechanism is particularly effective against gram-positive bacteria (e.g., Bacillus, Streptococcus), which lack protective outer membranes .

Key Steps in Lysozyme Activity:

1. Substrate Binding: The enzyme’s cleft accommodates a polysaccharide chain of 6 amino sugars.

2. Hydrolysis: Catalytic residues (e.g., Glu35, Asp52 in hen egg white lysozyme) facilitate bond cleavage.

3. Cell Wall Disruption: Repeated enzymatic attacks weaken peptidoglycan, leading to bacterial rupture .

Therapeutic Applications

Lysozyme demonstrates broad therapeutic potential beyond antimicrobial defense, supported by preclinical and clinical studies.

Antibacterial and Antiviral Effects

• Gram-Positive Infections: Effective against Staphylococcus aureus, Streptococcus pneumoniae, and Bacillus subtilis .

• Antiviral Activity: Inhibits HIV-1, hepatitis viruses, and COVID-19 spike protein-induced inflammation .

• Synergy with Antibiotics: Enhances the efficacy of β-lactams and aminoglycosides by permeabilizing bacterial membranes .

Anti-Cancer and Anti-Inflammatory Roles

Clinical and Dietary Uses

• Pediatric Nutrition: Human lysozyme in breast milk protects infants from diarrhea caused by E. coli and rotavirus. Transgenic goats producing human lysozyme aim to replicate this benefit for non-breastfed children .

• Food Preservation: Inhibits Clostridium tyrobutyricum and coliform bacteria in dairy products .

• Ophthalmic Protection: Maintains conjunctival health by preventing bacterial colonization .

Comparative Efficacy: Human vs. Hen Egg White Lysozyme

Challenges and Future Directions

Limitations:

• Gram-Negative Efficacy: Limited due to outer membrane protection.

• Thermal Sensitivity: Human lysozyme loses activity rapidly at high temperatures .

Research Opportunities:

• Marine Lysozymes: Exploring novel variants from marine organisms with broader antimicrobial spectra .

• Nanoparticle Delivery: Enhancing bioavailability for targeted cancer or viral therapies .

• Structural Engineering: Designing lysozyme variants with improved thermal stability or specificity .