Phage Therapy Study Reveals RNA-Based Infection Control

Key Takeaways (Quick Summary)

• Researchers uncovered how bacteriophages use a small RNA molecule (PreS) to control bacterial gene expression.
• PreS enhances phage DNA replication by increasing bacterial DnaN protein production.
• This RNA-based mechanism adds a new dimension to phage biology beyond viral proteins.
• The discovery supports future development of precision phage therapy against antibiotic-resistant infections.

Phage Therapy Research Responds to the Growing Antibiotic Resistance Crisis

Antibiotic resistance remains a major global health challenge, with projections estimating up to 10 million deaths annually by 2050 due to drug-resistant infections. As traditional antibiotics lose effectiveness, bacteriophages, viruses that selectively infect bacteria, are gaining attention as a targeted therapeutic option.

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A new study from the Hebrew University of Jerusalem reveals a previously unknown strategy used by bacteriophages to control bacterial cells. Instead of relying only on viral proteins, phages can deploy a small RNA molecule, called PreS, to redirect bacterial machinery and accelerate viral replication.

How PreS RNA Reprograms Bacterial Cells

The research team identified PreS as a post-transcriptional regulator that operates after bacterial genes have already been transcribed. Using RNA interaction mapping (RIL-seq), investigators showed that PreS binds directly to bacterial messenger RNAs.

A critical target is the dnaN mRNA, which encodes DnaN, a protein essential for DNA replication. Under normal conditions, this mRNA folds into a structure that limits ribosome access. PreS alters this structure, allowing ribosomes to translate the message more efficiently.

For healthcare professionals, this mechanism highlights how RNA-based regulation can rapidly reshape bacterial physiology during infection, an insight with direct relevance to antimicrobial research.

Why This Discovery Matters for Phage Therapy

By increasing DnaN production, PreS enables faster viral DNA replication and earlier bacterial cell lysis. When PreS was removed or its binding site disrupted, phages showed delayed replication and reduced infectivity.

Notably, PreS is conserved across multiple related phages, suggesting a shared RNA toolkit among viruses. This challenges the long-held assumption that phage control depends mainly on proteins and introduces RNA as a critical factor in infection efficiency.

For clinicians and researchers, understanding these molecular controls opens opportunities to design more predictable and effective phage-based treatments, particularly for multidrug-resistant infections.

Toward Smarter Antimicrobial Alternatives

As interest in phage therapy grows, insights like the PreS mechanism provide a scientific foundation for engineering phages with optimized performance and safety. Even well-studied viruses such as phage lambda continue to reveal new layers of complexity, underscoring the importance of basic research in shaping future clinical tools.

Source:

The Hebrew University of Jerusalem