Identification of a New Antimicrobial, Desertomycin H, Utilizing a Modified Crowded Plate Technique

Area of Science:

• Microbiology
• Natural Product Chemistry
• Drug Discovery

Background:

• Antibiotic-resistant bacteria pose a significant global health threat, necessitating novel antimicrobial compounds.
• Many bacterial genomes contain silent biosynthetic gene clusters with potential for producing antimicrobials, but activation methods are poorly understood.

Purpose of the Study:

• To develop and validate a new method, the modified crowded plate technique (mCPT), for activating silent biosynthetic gene clusters.
• To discover novel antimicrobial natural products from previously uncultured or transcriptionally silent microbial sources.

Main Methods:

• The modified crowded plate technique (mCPT) was employed, leveraging complex microbial interactions to induce antimicrobial production.
• Over 1400 microbial isolates were screened, with subsequent bioactivity assays and mass spectrometry used for characterization.
• The Tiny Earth educational program facilitated the large-scale screening process.

Main Results:

• The mCPT successfully elicited antimicrobial production from silent gene clusters.
• 62 isolates demonstrated activity against multidrug-resistant pathogens.
• Six isolates yielded extracts with potent activity against vancomycin-intermediate resistant *Staphylococcus aureus*.
• A new macrolactone metabolite, desertomycin H, was identified.

Conclusions:

• The mCPT is an effective strategy for discovering antibiotics from silent gene clusters.
• This approach significantly enhances the efficiency of identifying microbes with latent antibiotic-producing capabilities.
• The findings open new avenues for natural product-based antibiotic discovery.