Genome Informatics 2015 Bacteriocin Discovery
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A bacteriocin discovery pipeline called BOA. Bacteriocin are ribosomal synthesize anti bacterial compounds. BOA provides leads for bacteriocin discovery
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Genome Informatics 2015 Bacteriocin Discovery
- 1. Iddo Friedberg, PhD Bioinformatics and Computational Biology Iowa State University @iddux Finding Bacteriocins using BOA
- 2. Antibiotic resistance WHO (2014): “A problem so serious that it threatens the achievements of modern medicine... A post-antibiotic era, in which common infections and minor injuries can kill, far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century.”
- 3. Antibiotic Resistance Nature Chemical Biology 3, 541 - 548 (2007)
- 4. Decline in Antiobiotic Approval
- 5. Avoiding antbiotic resistance ● Using less antibiotics ● Narrow-spectrum drugs ● Harvest more natural compounds
- 6. The Wide World of Bacteriocins Antimicrobial Peptides Nisin A Microcin B17 Berninamycin A Microcin J25 Bacteriocin AS-48 Virulence Factors Streptolysin S Listeriolysin S Clostridiolysin S CylLL + CylLS Signaling Peptides RNPP/Rgg Agr Gly-Gly
- 7. Bacteriocins Antibiotics Synthesis Ribosomal Secondary metabolite Bioactivity spectra Mostly narrow Mostly broad Intensity of bioactivity Active at nano-to- micro molar range Active at micro-to-milli molar range Proteolytic enzyme degradability High Moderate-to-none Thermal stability High Low Active pH range Wide Narrow Possible mechanism of target cell developing resistance Adaptation through changes in cell membrane composition Genetically transferable determinant that inactivates the active compound Mode of action Pore formation, inhibition of cell wall biosynthesis Cell membrane or intercellular targets, inhibition cell wall biosynthesis
- 8. A B T C I P R K F E G
- 9. A B T C I P R K F E G
- 10. A B T C I P R K F E G NisB NisC NisT NisP
- 11. A B T C I P R K F E G NisB NisC NisT NisP
- 12. A B T C I P R K F E G NisB NisC NisT NisP
- 13. A B T C I P R K F E G NisB NisC NisT NisP
- 14. A B T C I P R K F E G NisB NisC NisT NisP NisF NisF NisE NisG NisI
- 15. A B T C I P R K F E G NisB NisC NisT NisP NisF NisF NisE NisG NisI NisK NisR
- 16. A B T C I P R K F E G NisB NisC NisT NisP NisF NisF NisE NisG NisI NisK NisR
- 17. A B T C I P R K F E G NisB NisC NisT NisP NisF NisF NisE NisG NisI NisK NisR
- 18. Looking for more bacteriocins
- 19. Looking for more bacteriocins
- 20. ? Bacteriocins may not be homologous, or even detectable as ORFs
- 21. So how do we find more bacteriocins? Antimicrobial Peptides Nisin A Microcin B17 Berninamycin A Microcin J25 Bacteriocin AS-48 Virulence Factors Streptolysin S Listeriolysin S Clostridiolysin S CylLL + CylLS Signaling Peptides RNPP/Rgg Agr Gly-Gly
- 22. ? Use the homologs we have: genomic-context
- 24. LC-Set BAGEL BOA Bacteriocin Operon Associator
- 25. LC-Set BAGEL BLAST vs. GenBank BOA Bacteriocin Operon Associator
- 26. LC-Set BAGEL BLAST vs. GenBank Within 50kb of toxin gene BOA Bacteriocin Operon Associator
- 27. LC-Set BAGEL BLAST vs. GenBank Within 50kb of toxin gene pHMM HMMER pHMM pHMM pHMM pHMM BOA Bacteriocin Operon Associator
- 28. LC-Set BAGEL BLAST vs. GenBank Within 50kb of toxin gene pHMM HMMER pHMM pHMM pHMM pHMM Clique Filter BOA Bacteriocin Operon Associator
- 32. BAGEL v. BOA
- 34. Method Found BAGEL 453 BOA + Toxin genes 1,003 BOA – Toxin genes 83
- 36. Top 3 Genomes: Different Ecosystems Streptococcus equi Streptomyces griseus Leifsonia xyli
- 37. Summing Up ● Annotated genbank files with all predicted bacteriocin blocks are available ● Need more curated bacteriocin blocks for training ● Explore use of feature vectors with different combinations / weights of context genes ● Feed into experiments ← → and back ● https://github.com/idoerg/BOA ● Paper & data in production BMC Bioinformatics ● http://arxiv.org/abs/1510.06008
- 38. Thanks Jamie Morton Stefan Freed Shaun Lee
- 39. Bioinformatics & Computational Biology PhD Program ● Well-established program, since 2000 ● Strengths in: genomics, structural bioinformatics, evolution, bioengineering ● NSF Training grant in plant phenomics ● $$$ from: Graduate College, Vice Provost Presidential Initiative Fellowships; Students take part in major plant and pharmaceutical company internships ● Recent Big Data presidential initiative faculty hires in metagenomics, phylogenetics, protein function prediction & more. ● Apply by February 15
- 40. Join the Friedberg Lab http://iddo-friedberg.net
- 42. Biosynthesis of Bacteriocins Gabrielsen et al. J. Bacteriol. 2014;196:911-919
- 44. Streptococcus equi Streptomyces griseu Lefsonia xyli Pusillimonas sp. Rhodosprillum rubru Streptococcus salivarius Stretomyces sp. Streptomyces pratensis Symbiobacterium thermophilum Thermotoga neopolitana Sterptococcus equi (8)
- 45. Biosynthesis of Bacteriocins Gabrielsen et al. J. Bacteriol. 2014;196:911-919