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Bacteriophage Effectiveness for Biocontrol of Foodborne Pathogens Evaluated via High-Throughput Settings
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Bacteriophage Effectiveness for Biocontrol of Foodborne Pathogens Evaluated via High-Throughput Settings

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Engineered phage-derived lysins effectively kill mycobacterial pathogens

Adel Abouhmad1, Jana Kassaliete2, Camilla Davids2

  • 1Division of Biotechnology, Department of Chemistry, Kemicentrum, Lund University, Box 124, Lund SE-221 00, Sweden; Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt.

Trends in Biotechnology
|March 31, 2026
PubMed

Insights

Researchers developed a novel mycolysin platform using phage enzymes to overcome mycobacterial cell wall barriers. This approach shows promise for developing next-generation antimycobacterial therapies against resistant strains.

Area of Science:

  • Biotechnology
  • Microbiology
  • Drug Discovery

Background:

  • Antimicrobial resistance in mycobacteria is a significant global health threat.
  • The complex mycobacterial cell wall impedes drug penetration, requiring lengthy treatments.
  • Mycobacteriophages possess enzymes capable of degrading the mycobacterial cell wall.

Purpose of the Study:

  • To engineer a modular mycolysin platform combining phage enzymes with cell-penetrating moieties.
  • To screen and identify potent mycolysin candidates against pathogenic mycobacteria.
  • To evaluate the efficacy and safety of lead mycolysin candidates.

Main Methods:

  • Utilized VersaTile shuffling technology to create chimeric mycolysin libraries.
  • Screened libraries against Mycobacterium smegmatis and Mycobacterium bovis Bacillus Calmette-Guérin (BCG).
  • Assessed minimum inhibitory concentrations (MICs), intracellular efficacy, serum stability, cytotoxicity, and in vivo efficacy.

Main Results:

  • Identified potent mycolysin candidates with MICs as low as 1.28 μg/ml against M. bovis BCG.
  • Demonstrated intracellular efficacy, serum stability, and noncytotoxicity of lead compounds.
  • Showcased in vivo proof-of-concept efficacy in rat models and synergy with rifampicin.

Conclusions:

  • The developed mycolysin platform effectively targets mycobacterial cell walls.
  • These phage-derived enzymes represent a promising strategy for next-generation antimycobacterial therapies.
  • The modular platform offers a versatile framework for engineering novel antimicrobials.
Keywords:
Lysin ALysin BVersaTile technologyantimicrobial resistancemycobacterial pathogensmycolysin

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