Science News from research organizations Scientists discover a bacterial kill switch and it could change the fight against superbugs Viruses may have exposed a critical weak spot in superbugs, opening the door to a new class of antibiotics. Date: February 28, 2026 Source: California Institute of Technology Summary: Drug-resistant bacteria are becoming harder to treat, pushing scientists to look for new antibiotic targets. Researchers have now discovered that several unrelated viruses disable a key bacterial protein called MurJ, which is essential for building the bacterial cell wall. High-resolution imaging shows these viral proteins lock MurJ into a single position, stopping cell wall construction and leading to bacterial death. Share: Facebook Twitter Pinterest LinkedIN Email FULL STORY Viruses may hold the blueprint for next-generation antibiotics—by revealing how to shut down a bacterial lifeline called MurJ. Here, three distinct phage Sgl proteins lock the flippase MurJ in an outward-facing state, providing a template for antibiotic discovery. Credit: Juliet Lee Scientists have revealed how viruses that infect bacteria shut down MurJ, a protein essential for building the bacterial cell wall. Remarkably, different viruses evolved separate proteins that all block MurJ in the same way, highlighting it as a promising new antibiotic target. The findings appear in the February 26 issue of Nature . The research was led by Yancheng Evelyn Li, a graduate student in the lab of Bil Clemons at Caltech. Clemons, the Arthur and Marian Hanisch Memorial Professor of Biochemistry, is the corresponding author. The Urgent Need for New Antibiotics Bacteria evolve quickly, and that adaptability is fueling a growing public health crisis. As Clemons explains, "Evolution is powerful, and in bacteria, resistance to antibiotics develops quickly. This means that we now deal with bacteria that are resistant to all the medicines that we have." He adds, "In the USA alone, tens of thousands of people die every year from antibiotic-resistant bacterial infections, and that number is rising rapidly. We need new antibiotics to combat this." With existing drugs losing effectiveness, researchers are searching for entirely new bacterial weak points. Targeting the Bacterial Cell Wall One long standing focus has been the pathway bacteria use to construct peptidoglycan, the rigid material that forms their cell wall. This process, called the peptidoglycan biosynthesis pathway, is especially attractive because peptidoglycan is found in bacteria but not in human cells. As Clemons notes, "Peptidoglycan is a unique feature of bacteria, and that makes it an attractive antibiotic target." Several antibiotics already disrupt this pathway. Penicillin, discovered by Alexander Fleming in the mid 20th century, blocks a late stage of peptidoglycan production. Related drugs such as amoxicillin work in a similar way. Key Proteins MraY, MurG, and MurJ Three essential proteins drive the movement of peptidoglycan building blocks across the bacterial inner membrane: MraY, MurG, and MurJ. These proteins help transport the components needed to assemble the cell wall outside the inner membrane barrier. If any one of them fails, peptidoglycan cannot be produced and the bacterium dies, making them promising drug targets. Although researchers understand much about how these proteins function, Clemons points out that important mechanistic details remain unclear. At present, no approved drugs directly inhibit these three proteins. Still, Clemons says there is potential. "We do know that we can find small molecules, either derived from nature or synthesized in chemical libraries, that will inhibit these proteins. Excitingly, recent discoveries have shown that bacteriophages have figured out how to target this pathway." How Bacteriophages Break Through Bacterial Defenses Bacteriophages, or phages, are viruses that infect bacteria. To survive, they must enter a bacterial cell, replicate, and then escape to infect others. Breaking out requires getting through the peptidoglycan layer. Clemons explains, "Getting back out means that they have to get past the peptidoglycan layer. Because it acts like chainmail, the phages get stuck if they can't break through it." The Clemons lab studies small phages that contain single stranded DNA or RNA. These viruses have compact genomes and rely on simple strategies to kill bacteria. In 2023, the team reported in Science on φX174, a phage with a long research history at Caltech. Viral Proteins That Disable MurJ Small phages rely on specialized protein antibiotics called single-gene lysis proteins, or Sgls (pronounced like "sigils"), to kill bacteria. Li and Clemons have focused on Sgls that target MurJ, one of the key cell wall proteins. MurJ acts as a flippase. It transports peptidoglycan precursors from the inside of the cell across the membrane so they can be incorporated