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Background <p>Antimicrobial peptides (AMPs) have advantages over traditional antibiotics in fighting against drug-resistant bacterial infections. Natural microbial communities are considered as the priority targets for next-generation AMP bioprospecting initiatives. While progress has been made in characterizing AMPs from the dominant microbial taxa in natural ecosystems, current research largely overlooks the biosynthetic potential of rare species. Given their distinct evolutionary pressures, rare species likely produce AMPs with novel structures and unconventional mechanisms of action.</p> Results <p>In this study, enrichment cultivation of a marine biofilm was conducted in 138 carbon source- and oxygen level-based conditions, followed by metagenomic sequencing using both Illumina and Nanopore platforms. Analysis of 435 high-quality genomes derived from the metagenomes suggests that these bacterial strains are significantly underrepresented (&lt; 0.01%) in global marine biofilm communities. Through multi-model prediction, we identified 3,054,472 candidate AMPs from the genomes, including 1048 high-confidence ones, thereby significantly expanding the previously known AMPSphere. Furthermore, AMPs derived from the rare bacterial species exhibit unique sequence characteristics, structural diversity, remarkable stability under diverse pH conditions and pepsin exposure, and strong therapeutic potential in animal models, reflecting their specialized adaptive and defensive strategies developed within ecological systems.</p> Conclusions <p>The features of the underexplored AMPs from low-abundance bacteria in marine biofilms provide valuable resources and theoretical foundations for the development of highly effective antimicrobial agents.</p> <p><MediaObject ID="MOESM3"> <VideoObject FileRef="MediaObjects/40168_2025_2326_MOESM3_ESM.mp4" VideoID="7R-Z4cmD4J_J53bRpdvvUz"> <Caption Language="En" xml:lang="en"> <CaptionContent> <p>Video Abstract</p> </CaptionContent> </Caption> </VideoObject> </MediaObject></p>

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Unlocking the unexplored AMPSphere in marine rare species

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月23日

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  • Shen Fan,
  • Jie Lu,
  • Han Cui,
  • Wei Ding,
  • Shunbo Li,
  • Jin Sun,
  • Yong-Xin Li,
  • Weipeng Zhang

摘要

Background

Antimicrobial peptides (AMPs) have advantages over traditional antibiotics in fighting against drug-resistant bacterial infections. Natural microbial communities are considered as the priority targets for next-generation AMP bioprospecting initiatives. While progress has been made in characterizing AMPs from the dominant microbial taxa in natural ecosystems, current research largely overlooks the biosynthetic potential of rare species. Given their distinct evolutionary pressures, rare species likely produce AMPs with novel structures and unconventional mechanisms of action.

Results

In this study, enrichment cultivation of a marine biofilm was conducted in 138 carbon source- and oxygen level-based conditions, followed by metagenomic sequencing using both Illumina and Nanopore platforms. Analysis of 435 high-quality genomes derived from the metagenomes suggests that these bacterial strains are significantly underrepresented (< 0.01%) in global marine biofilm communities. Through multi-model prediction, we identified 3,054,472 candidate AMPs from the genomes, including 1048 high-confidence ones, thereby significantly expanding the previously known AMPSphere. Furthermore, AMPs derived from the rare bacterial species exhibit unique sequence characteristics, structural diversity, remarkable stability under diverse pH conditions and pepsin exposure, and strong therapeutic potential in animal models, reflecting their specialized adaptive and defensive strategies developed within ecological systems.

Conclusions

The features of the underexplored AMPs from low-abundance bacteria in marine biofilms provide valuable resources and theoretical foundations for the development of highly effective antimicrobial agents.

Video Abstract