Direct Detection of Antibacterial-Producing Soil Isolates Utilizing a Novel High-Throughput Screening Assay

Area of Science:

• Microbiology
• Drug Discovery
• Biotechnology

Background:

• Antimicrobial resistance (AMR) is a growing global health threat, potentially leading to a post-antibiotic era.
• Current antibiotic discovery methods are slow, and synthetic compound screening has yielded limited success.
• Natural sources, particularly environmental bacteria, remain promising for novel antibiotic discovery.

Purpose of the Study:

• To develop a rapid and simple preliminary screening assay for identifying antibacterial-producing bacteria from natural sources.
• To overcome the laborious and time-consuming nature of traditional antibiotic discovery methodologies.
• To accelerate the discovery of novel antibiotics to combat antimicrobial resistance.

Main Methods:

• Development of the bioluminescent simultaneous antagonism (BSLA) assay.
• Utilizing luminescence in co-cultures of bioluminescent reporter bacteria and test bacteria in a 96-well plate format.
• Assessing antibacterial compound production based on the presence or absence of luminescence.

Main Results:

• The BSLA assay accurately distinguishes between antibacterial-producing and non-producing bacteria.
• Screening of 264 unknown soil isolates identified 10 antibacterial-producing isolates.
• The BSLA assay reduced the pool of isolates for downstream analysis by 96%.

Conclusions:

• The BSLA assay provides a simple, rapid, and effective method for pre-screening bacterial isolates for antibacterial production.
• This assay can be scaled for high-throughput screening, further optimizing the discovery pipeline.
• Coupled with advanced identification technologies, the BSLA assay can significantly fast-track the discovery of novel antimicrobials.