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Purpose <p>Carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) represents a critical global health threat for which existing antibiotics are increasingly inadequate. This study aimed to establish a comprehensive genomic framework for the rational prioritization of virulent <i>Acinetobacter</i> bacteriophages as therapeutic candidates.</p> Methods <p>We performed large-scale comparative genomic analysis of 340 virulent <i>Acinetobacter</i> bacteriophages, integrating phylogenetic reconstruction, pangenome analysis, CRISPR spacer-based host interaction mapping, Anti-CRISPR protein identification, and systematic antimicrobial resistance (AMR) gene screening.</p> Results <p>Genome sizes spanned a nearly 20-fold range, with a significant negative correlation between genome size and GC content (R² = 0.139, ρ = −0.630). Phylogenetic analysis revealed extensive divergence across multiple lineages with no dominant clade. Pangenome analysis identified 20,982 unique protein families, of which 76.2% were cloud genes, confirming a highly open genome architecture. CRISPR spacer matching yielded 1,480 high-confidence matches across 100 phage genomes, providing molecular evidence of broad historical infectivity. Anti-CRISPR profiling identified <i>Acinetobacter</i> phage XC1 as an exceptional therapeutic candidate harboring 55 predicted Anti-CRISPR proteins with canonical regulatory locus architecture. AMR screening identified 21 distinct AMR gene homologs (Loose RGI hits, 22.5 to 47.1% amino acid identity) distributed heterogeneously across the dataset, confirming abundant therapeutically clean candidates while flagging a subset warranting further scrutiny before therapeutic exclusion.</p> Conclusion <p>These findings provide a multi-criteria genomic framework for rational phage candidate prioritization against multidrug-resistant <i>Acinetobacter</i> infections, with direct implications for evidence-based phage therapy development.</p>

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Genomic landscape of 340 virulent Acinetobacter bacteriophages reveals anti-CRISPR–enriched candidates for therapeutic prioritization

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月6日

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  • S. M. Iqbal Mahamud,
  • Md. Sahim,
  • Mahjabin Sanam,
  • Jahin Fairuj Oishi,
  • Jarin Tabassum,
  • Nawshin Binte Shams,
  • Mahfuja Maisha Ansary

摘要

Purpose

Carbapenem-resistant Acinetobacter baumannii (CRAB) represents a critical global health threat for which existing antibiotics are increasingly inadequate. This study aimed to establish a comprehensive genomic framework for the rational prioritization of virulent Acinetobacter bacteriophages as therapeutic candidates.

Methods

We performed large-scale comparative genomic analysis of 340 virulent Acinetobacter bacteriophages, integrating phylogenetic reconstruction, pangenome analysis, CRISPR spacer-based host interaction mapping, Anti-CRISPR protein identification, and systematic antimicrobial resistance (AMR) gene screening.

Results

Genome sizes spanned a nearly 20-fold range, with a significant negative correlation between genome size and GC content (R² = 0.139, ρ = −0.630). Phylogenetic analysis revealed extensive divergence across multiple lineages with no dominant clade. Pangenome analysis identified 20,982 unique protein families, of which 76.2% were cloud genes, confirming a highly open genome architecture. CRISPR spacer matching yielded 1,480 high-confidence matches across 100 phage genomes, providing molecular evidence of broad historical infectivity. Anti-CRISPR profiling identified Acinetobacter phage XC1 as an exceptional therapeutic candidate harboring 55 predicted Anti-CRISPR proteins with canonical regulatory locus architecture. AMR screening identified 21 distinct AMR gene homologs (Loose RGI hits, 22.5 to 47.1% amino acid identity) distributed heterogeneously across the dataset, confirming abundant therapeutically clean candidates while flagging a subset warranting further scrutiny before therapeutic exclusion.

Conclusion

These findings provide a multi-criteria genomic framework for rational phage candidate prioritization against multidrug-resistant Acinetobacter infections, with direct implications for evidence-based phage therapy development.