In-Depth Notes on Phages and Therapeutic Applications

Introduction

  • Graham Hatful, Professor of Biological Sciences at the University of Pittsburgh and lead scientist for the Sea Phages program, presents at a symposium.
  • Discusses bacteriophages and their therapeutic potential
  • Topics to cover:
    • Phage discovery and genomics
    • Insights into phage structures and interactions with bacterial hosts
    • Advances in therapeutic applications of mycobacteria phages

Phage Discovery and Genomics

  • Phages DB homepage overview:
    • Total phage collection exceeds 28,000, with 5,400 sequenced and annotated.
    • 14,000 mycobacteria phages isolated, with 2,600 sequenced.
  • Isolation statistics from the past year:
    • 2,880 phages isolated; 580 sequenced.
    • Breakdown by host species:
    • 232 mycobacterium phages
    • 122 other phages, 68 Donia, 82 microbacterium, 50 kurta bacterium, and 25 streptomycin.
  • Heterogeneous representation of phages within clusters; notable clusters:
    • Cluster A: 850 phages
    • Cluster B: 458 phages
    • Singletons and fewer represented clusters
  • New clusters emerging:
    • Cluster A1 with two newly sequenced phages:
    • "Saint Augustine" (isolated 2023)
    • "Causa" (isolated January 2024)
  • Characteristics of A1 phages:
    • Large genomes (~101 kb, 180 ORFs and ~17 tRNAs)
    • Likely lytic due to absence of lysogenic genes

Insights into Phage Structures and Interactions

  • Study of high-resolution phage structures (BxB1) using cryo-electron microscopy:
    • Significance of the serine integrase enzyme in genome engineering
    • Collaboration for structural insights and challenges faced during engineering attempts for SARS-CoV-2 antigen display on capsid
  • Tail tip structures:
    • Binding to host cell surfaces; key protein interactions
    • Differences in tail proteins and novel findings within the structures of phages Muddy and Beeps
  • Focus on understanding which surface structures interact with the target bacterial cell wall:
    • Transposon mutagenesis to identify bacterial mutants resistant to phage
    • Involvement of trehalose polyflates in bacterial infection and phage capture

Advances in Therapeutic Applications

  • Overview of clinical phage therapy cases:
    • Use of phages against Mycobacterium abscessus infections
    • 550 clinical isolates received for analysis
  • Phage infection efficiency dependent on bacterial colony type (smooth vs rough):
    • Rough strains typically yield better infection outcomes
  • Assessment of therapeutic efficacy:
    • Various assays to measure phage-induced bacterial cell death
    • Observations of co-infections with smooth and rough strains in patients
  • Example of phage therapy case study with different outcomes based on strain types
  • Challenges facing broad therapeutic use due to genetic variability in isolates

Conclusion

  • Understanding the complexity of phage diversity, structure, and their interactions with bacterial hosts is critical for developing effective therapies
  • Hopeful about advancements in genomic studies and potential therapeutic applications
  • Grateful acknowledgment of contributors to phage discovery and research

Notes

  • Krista Freeman available for Q&A after the presentation