Engineered Lysins With Customized Lytic Activities Against Enterococci and Staphylococci.

Area of Science:

• Microbiology
• Biotechnology
• Antimicrobial Resistance

Background:

• Multidrug-resistant bacteria pose a significant threat, rendering many infections untreatable with current antibiotics.
• Bacteriophages encode lysins, enzymes targeting bacterial peptidoglycan, showing promise as novel antimicrobials.
• Lysins possess modular structures with catalytic (CD) and cell wall binding domains (CBD), allowing for engineering.

Purpose of the Study:

• To engineer chimeric lysins with altered lytic spectra and species specificity.
• To investigate the roles of catalytic and cell wall binding domains in determining lysin activity.
• To explore the potential of engineered lysins as targeted antimicrobial agents.

Main Methods:

• Construction of two chimeric lysins by swapping the CBDs of parent lysins with distinct lytic spectra.
• Evaluation of the lytic spectra of chimeric lysins against enterococci and staphylococci.
• Analysis of species-specific activity using flow cytometry and confocal microscopy.

Main Results:

• Chimeric lysins exhibited customized lytic spectra, differing from their parent lysins.
• The chimeric lysin P10N-V12C showed species specificity, targeting E. faecalis and staphylococci but not E. faecium.
• E. faecium treated with P10N-V12C showed compromised membranes but remained morphologically intact.

Conclusions:

• While CBD significantly influences lytic spectrum, the CD also plays a crucial role, particularly in achieving species specificity.
• Engineered lysins offer a promising strategy for developing targeted antimicrobials against resistant bacteria.
• Further research into lysin domain interactions can lead to novel therapeutic solutions for bacterial infections.