Discovery of antibiotics in the archaeome using deep learning
Torres, M. D. T.; Wan, F.; de la Fuente, C.
10.1101/2024.11.15.623859 bioRxivShow abstract
Antimicrobial resistance (AMR) is one of the greatest threats facing humanity, making the need for new antibiotics more critical than ever. While most antibiotics have traditionally been derived from bacteria and fungi, archaea--a distinct and underexplored domain of life--offer a largely untapped reservoir for antibiotic discovery. In this study, we leveraged deep learning to systematically explore the archaeome, uncovering promising new candidates for combating AMR. By mining 233 archaeal proteomes, we identified 12,623 molecules with potential antimicrobial activity. These newly discovered peptide compounds, termed archaeasins, exhibit unique compositional features that differentiate them from traditional antimicrobial peptides, including a distinct amino acid profile. We synthesized 80 archaeasins, 93% of which demonstrated antimicrobial activity in vitro. Notably, in vivo validation identified archaeasin-73 as a lead candidate, significantly reducing bacterial loads in mouse infection models, with effectiveness comparable to established antibiotics like polymyxin B. Our findings highlight the immense potential of archaea as a resource for developing next-generation antibiotics.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Cell-free biosynthesis combined with deep learning accelerates de novo-development of antimicrobial peptides 97%
- Biosynthetic Enzyme-guided Disease Correlation Connects Gut Microbial Metabolites Sulfonolipids to Inflammatory Bowel Disease Involving TLR4 Signaling 95%
- An anti-virulence drug targeting the evolvability protein Mfd protects against infections with antimicrobial resistant ESKAPE pathogens 94%
Similar papers in this journal
- More than just an Eagle Killer: The freshwater cyanobacterium Aetokthonos hydrillicola produces highly toxic dolastatin derivatives 94%
- The Amphibian Antimicrobial Peptide Uperin 3.5 is a Cross-α/Cross-β Chameleon Functional Amyloid 93%
- Reconstitution of the S. aureus agr quorum sensing pathway reveals a direct role for the integral membrane protease MroQ in pheromone biosynthesis 93%
Similar papers in this journal
- Armeniaspirols inhibit the AAA+ proteases ClpXP and ClpYQ leading to cell division arrest in Gram-positive bacteria 95%
- Identification of an inhibitory pocket in falcilysin provides a new avenue for malaria drug development 93%
- Structure-aided development of small molecule inhibitors of ENPP1, the extracellular phosphodiesterase of the immunotransmitter cGAMP 93%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.