Beyond antibiotics: phage-encoded lysins against Gram-negative pathogens

Area of Science:

• Microbiology
• Biotechnology
• Drug Discovery

Background:

• Antibiotic resistance is a growing global health crisis, driven by overuse of existing drugs.
• The pipeline for new antibiotics is insufficient, particularly against critical Gram-negative pathogens.
• Antimicrobial resistance (AMR) poses a significant threat to public health worldwide.

Purpose of the Study:

• To review the potential of phage-encoded lysins as alternatives to conventional antibiotics.
• To focus on the challenges and opportunities of using lysins against WHO priority Gram-negative pathogens.
• To discuss the development of lysins as therapeutics within the current regulatory landscape.

Main Methods:

• Review of existing literature on antimicrobial resistance and phage-encoded lysins.
• Analysis of the efficacy and safety of lysins against Gram-positive and Gram-negative bacteria.
• Examination of strategies to overcome the outer membrane barrier in Gram-negative bacteria.

Main Results:

• Lysins have shown efficacy against Gram-positive pathogens, with some in clinical development.
• The outer membrane of Gram-negative bacteria presents a significant challenge for lysin activity.
• Engineered lysins and combinations with outer membrane permeabilizers are being investigated.

Conclusions:

• Phage-encoded lysins (enzybiotics) offer a promising alternative to antibiotics, especially for Gram-negative infections.
• Overcoming the outer membrane barrier is crucial for the therapeutic application of lysins against Gram-negative bacteria.
• Further research and regulatory considerations are needed to advance lysins as viable treatments for AMR.