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PreprintCited by 79Genomics and Phylogenetic StudiesAntimicrobial Peptides and ActivitiesMicrobial Natural Products and Biosynthesis

AllTheBacteria: a community resource empowers biology and discovers novel peptide antibiotics

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Hunt, Martin, Torres, Marcelo D. T., Alikhan, Nabil-Fareed, Anderson, Daniel, Andreani, Maria Luiza, Blom, Josefin, Bouras, George, Brinkman, Fiona S.L. +37 more·2024·bioRxiv (Cold Spring Harbor Laboratory)
DOI 10.1101/2024.03.08.584059PMC PMC13370402
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Abstract

Public microbial genomes encode an immense record of biological diversity, evolution and molecular function, but much of this information remains difficult to reuse because raw sequencing data are not uniformly assembled, quality controlled, annotated or searchable at scale. Here we present AllTheBacteria, an open, community-built resource that transforms public bacterial short-read whole-genome sequencing reads into a uniformly processed discovery platform. The current analysed release contains 2,440,377 high-quality bacterial and archaeal genomes from 11,273 species, together with standardized taxonomic assignments, genome annotations, antimicrobial resistance calls, antiphage-defence annotations, protein structure predictions and AI-ready sequence tables. We show that this infrastructure enables applications that would otherwise be impractical, from global sequence search and outbreak contextualization to pangenome method development, antimicrobial resistance reservoir mapping and antiphage-defence ecology. As a stringent experimental demonstration, we mined 3,919,096 encrypted peptide fragments from AllTheBacteria proteomes using our deep learning model APEX 1.1, identifying 1,867 candidates with predicted antimicrobial activity. We synthesized 24 representative peptides and tested them against 20 clinically relevant bacterial strains, including antibiotic-resistant pathogens. Multiple peptides showed low-micromolar activity, membrane-responsive conformational transitions and selective envelope perturbation. A lead molecule, ATB20, reduced Acinetobacter baumannii burden in a murine skin abscess model with efficacy comparable to polymyxin B and no overt toxicity. Together, these results establish AllTheBacteria as both a foundational community resource for microbiology and a renewable engine for AI-guided antimicrobial discovery.

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  • Across all genomes in the newly curated AllTheBacteria database, the 10 most sequenced species make up 77% of the 1.9 million genomes.

    “Across all genomes in the newly curated AllTheBacteria database, the 10 most sequenced species make up 77% of the 1.9 million genomes5.”

    From A phylogenetic approach to comparative genomics (2025) · cites this paper as [5]

    The section “A community-built atlas of bacterial and archaeal genomes” reports 2,440,377 genomes in the current release, contrary to the claimed total of 1.9 million. It notes a bias toward frequently sequenced organisms but does not give the claimed 77% share for the ten most sequenced species. (LLM, conf=0.84)

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Authors
Hunt, M., Torres, M. D. T., Alikhan, N.-F., Anderson, D., Andreani, M. L., Blom, J., Bouras, G., Brinkman, F. S. L., Carroll, L. M., Croxen, M. A., Floto, R. A., Hall, M. B., Hawkey, J., Horsfield, S. T., Jia, B., Lacey, J. A., Lee, H.-S., Lima, L., MacAlasdair, N., Mallawaarachchi, S., Matlock, W., Moustafa, A. M., Petit, R., Ramnath, V., Raghuram, V., Russell, M. J., Sanderson, T., Saratto, T., Schwengers, O., Seemann, T., Shaw, L. P., Shen, W., Thomson, N., Tonkin-Hill, G., Toussaint, J., Viet, T. L., Wachsmann, J. V., Wan, F., Weimann, A., Wheatley, R. M., Wiatrak, M., Xie, O., Fuente-Nunez, C. D. L., Lees, J. A., & Iqbal, Z.
Affiliations
  • European Bioinformatics Institute (GB)
  • Norwich Research Park (GB)
  • Simon Fraser University (CA)
  • Umeå Centre for Microbial Research (SE)
  • University of Alberta (CA)
  • University of Cambridge (GB)
  • The University of Queensland (AU)
  • Monash University (AU)
  • The University of Melbourne (AU)
  • University of Pennsylvania (US)
  • University of Bath (GB)
  • Children's Hospital of Philadelphia (US)
  • Dept Bison Wrangling, Cowboy University, USA
  • London School of Hygiene & Tropical Medicine (GB)
  • Justus-Liebig-Universität Gießen (DE)
  • University of Bristol (GB)
  • Second Affiliated Hospital of Chongqing Medical University (CN)
  • Wellcome Sanger Institute (GB)
  • Theiagen Genomics, USA
  • Queen's University Belfast (GB)
  • Machine Biology Group, Departments of Psychiatry and Microbiology, Institute for Biomedical Informatics, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania; Philadelphia, Pennsylvania 19104, USA
Corresponding author
Iqbal, Zamin
ORCID
Venue
bioRxiv (Cold Spring Harbor Laboratory)
Publisher
openRxiv
Published
2024-03-11
DOI
10.1101/2024.03.08.584059
PMC
PMC13370402
OpenAlex
W4392644277
Cited by
79
References
0
Citations by year
2026: 34 · 2025: 35 · 2024: 10
Type
posted content
Language
en
Open access
Licence
Locations
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (Queen's University Belfast) (submittedVersion, cc-by)
Funders
  • National Health and Medical Research Council Australia (2034741)
  • SciLife Lab and Wallenberg Data Driven Life Science Program (KAW 2020.0239)
  • BBSRC (BB/CCG1860/1)
  • UKRI (UKRI2317)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
  • Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
  • Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
Keywords
bacterial genomes, peptide antibiotics, antimicrobial resistance, pan-genome, genome annotation, taxonomic classification, APEX model, Acinetobacter baumannii, skin abscess, antibiotic-resistant pathogens, protein structure prediction

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