Tel Aviv [Israel], December 18 (ANI/TPS): A tiny viral switch discovered by Israeli and American scientists could open a new front in the fight against antibiotic-resistant infections, a global health threat projected to kill up to 10 million people annually by 2050.

Scientists at the Hebrew University of Jerusalem have revealed that bacteriophages--viruses that infect bacteria--use a small RNA molecule to hijack bacterial cells, a mechanism that had never been described before, offering fresh insights for future phage-based therapies.

The study, led by Sahar Melamed and her team, including PhD student Aviezer Silverman, MSc student Raneem Nashef, and computational biologist Reut Wasserman, in collaboration with Prof. Ido Golding from the University of Illinois Urbana-Champaign, focused on a tiny viral RNA called PreS.

Unlike most prior research, which concentrated on viral proteins, this study showed that even one of the most studied phages, lambda, uses RNA to directly manipulate bacterial gene expression.

'This small RNA gives the phage another layer of control,' Melamed said. 'By regulating essential bacterial genes at exactly the right moment, the virus improves its chances of successful replication. What astonished us most is that phage lambda, studied for more than 75 years, still hides secrets. Discovering an unexpected RNA regulator in such a classic system suggests we have only grasped a single thread of what may be a much richer network of RNA-mediated control in phages.'

The researchers discovered that PreS acts like a molecular 'switch' inside infected bacteria, targeting specific bacterial messenger RNAs. One key target is the message that codes for DnaN, a protein essential for DNA replication. PreS binds to a normally folded portion of this mRNA, unfolds it, and makes it easier for the bacterial protein-making machinery to translate it. The result is more DnaN protein, faster viral DNA replication, and a more efficient infection. When PreS is removed or its binding site disrupted, the phage weakens, multiplies more slowly, and its destructive phase is delayed.

'This mechanism had never been seen before in phages,' said Silverman. 'It shows that even the smallest viral molecules can play a decisive role in infection, giving the virus a subtle but powerful advantage over its host.'

The discovery is particularly striking because small RNAs were not previously considered major players in phage biology. Yet PreS is highly conserved across related viruses, suggesting that many phages may share a hidden 'toolkit' of RNA regulators, a field scientists are only beginning to explore.

Understanding how phages control bacterial cells is crucial for both fundamental biology and potential medical applications. With antibiotic resistance rising worldwide, phage therapy--using viruses to selectively attack bacteria--is gaining attention as a flexible, targeted alternative to conventional drugs. Discoveries like PreS provide a blueprint for designing smarter phages that are safer, more predictable, and more effective in combating drug-resistant infections.

'Even the smallest viral molecules can have a huge impact on whether an infection succeeds,' Melamed said. 'By learning how phages manipulate their hosts at this microscopic level, we can begin to engineer viruses that are both powerful and precise in the fight against antibiotic resistance.'

Understanding how PreS manipulates bacterial cells could help scientists design smarter phage therapies that are more efficient at targeting harmful bacteria, particularly strains resistant to antibiotics. By harnessing these RNA-based mechanisms, researchers could develop precision treatments capable of attacking multi-drug-resistant infections that conventional antibiotics cannot touch.

Beyond medicine, the findings may also have applications in synthetic biology, allowing engineered phages or bacteria to be used in industrial processes, microbiome management, or controlling biofilms, turning a once-hidden viral strategy into a versatile tool for both health and technology. (ANI/TPS)