Scientists at the Hebrew University of Jerusalem have identified a mechanism by which bacteriophages, viruses that infect bacteria, manipulate bacterial cells to increase their own replication. The study highlights the role of a small RNA molecule called PreS, which acts as a genetic switch within the bacterial cell.
The research team, led by Dr. Sahar Melamed and including PhD student Aviezer Silverman, MSc student Raneem Nashef, computational biologist Reut Wasserman, and Prof. Ido Golding from the University of Illinois Urbana-Champaign, discovered that PreS enables phages to alter how bacterial genes function during infection.
PreS attaches to specific bacterial messenger RNAs (mRNAs), particularly targeting the message responsible for producing DnaN—a protein central to DNA replication in bacteria. By binding to this mRNA, PreS changes its structure so ribosomes can access it more easily, resulting in increased production of DnaN and faster viral DNA copying.
When researchers removed PreS or disrupted its binding site on the mRNA, they observed that phage replication slowed and the process leading to cell destruction was delayed.
"This small RNA gives the phage another layer of control," says Dr. Sahar Melamed. "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, one of the most intensively studied viruses 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 an entirely richer, more intricate tapestry of RNA-mediated control in phages."
The study suggests that small RNAs like PreS are conserved among related viruses and could represent a common toolkit used by many phages—an area previously underexplored in phage biology.
Understanding these mechanisms is seen as important due to rising antibiotic resistance worldwide. Projections indicate that drug-resistant infections could cause up to 10 million deaths annually by 2050 if new solutions are not found. Phage therapy is being considered as an alternative treatment strategy since it uses viruses that specifically target bacteria rather than relying solely on antibiotics.
Findings such as those about PreS may inform future development of engineered phages designed for greater safety and effectiveness against antibiotic-resistant bacteria.
