Unlocking the unexplored AMPSphere in marine rare species

Area of Science:

• Microbiology
• Bioprospecting
• Genomics

Background:

• Antimicrobial peptides (AMPs) offer advantages over traditional antibiotics for combating drug-resistant bacteria.
• Natural microbial communities are key targets for AMP discovery, but rare species are often overlooked.
• Rare microbes may produce AMPs with novel structures and mechanisms due to distinct evolutionary pressures.

Purpose of the Study:

• To explore the biosynthetic potential of rare bacterial species in marine biofilms for novel AMP discovery.
• To expand the known repertoire of AMPs by investigating underrepresented microbial taxa.
• To characterize the properties and therapeutic potential of AMPs from rare marine bacteria.

Main Methods:

• Enrichment cultivation of marine biofilms under diverse conditions (138 variations).
• Metagenomic sequencing using Illumina and Nanopore platforms.
• Bioinformatic analysis of 435 high-quality genomes to identify candidate AMPs using multi-model prediction.

Main Results:

• Identified 3,054,472 candidate AMPs, including 1048 high-confidence AMPs, significantly expanding the AMPSphere.
• Characterized AMPs from rare bacterial strains ( < 0.01% abundance) exhibiting unique sequences and structures.
• Demonstrated remarkable stability (pH, pepsin) and strong therapeutic potential in animal models for these novel AMPs.

Conclusions:

• Underexplored AMPs from low-abundance marine bacteria represent valuable resources for antimicrobial development.
• The unique features of these AMPs provide theoretical foundations for creating highly effective antimicrobial agents.
• This study highlights the importance of investigating rare microbial species for novel drug discovery.