Whole-Cell Bioreporter-Based Assay for Detecting Fungal-Derived β-Lactamase Inhibitors.

Area of Science:

• Microbiology
• Biotechnology
• Drug Discovery

Background:

• Beta-lactam antibiotics are crucial but face resistance from microbial beta-lactamase enzymes.
• Developing effective beta-lactamase inhibitors is vital to preserve antibiotic efficacy.
• Current screening methods for inhibitors are complex and limit drug development.

Purpose of the Study:

• To develop a sensitive and efficient bioassay for screening beta-lactamase inhibitory compounds.
• To identify novel natural inhibitors of beta-lactamase enzymes.
• To validate the utility of bioluminescent bacteria as bioreporters for this purpose.

Main Methods:

• A novel bioassay was designed using bioluminescent indicator bacteria as bioreporters.
• The bioassay was optimized using commercial antibiotics and known beta-lactamase inhibitors.
• The assay was employed to screen for inhibitors from coral-associated fungi, specifically Penicillium spinulosum.

Main Results:

• The developed bioassay successfully identified compounds with anti-beta-lactamase activity from Penicillium spinulosum.
• Bioreporter bacteria demonstrated a concentration-dependent response to combined antibiotics and inhibitors.
• The study confirmed the potential of this bioassay for discovering beta-lactamase inhibiting compounds.

Conclusions:

• A novel, sensitive bioassay utilizing bioluminescent bacteria was established for beta-lactamase inhibitor discovery.
• Coral-associated fungi, like Penicillium spinulosum, are a promising source of natural beta-lactamase inhibitors.
• This assay facilitates the development of combination therapies to combat antibiotic resistance.