Jerusalem, 2 February, 2026 (TPS-IL) — Bacteria have hijacked ancient viral machinery to recognize and attack an astonishing range of cell types, a discovery that could transform Medicine and biotechnology, a team of Israeli and Chinese scientists said.
The research shows that bacteria repeatedly retarget the same molecular injection system by swapping the protein that binds to cells. By uncovering thousands of these interchangeable receptor-binding proteins hidden in bacterial genomes, the study solves a long-standing biological mystery and provides a ready-made toolkit for delivering drugs, enzymes, or other molecules into specific human, animal, or plant cells.
The focus of the study is extracellular contractile injection systems, or eCISs — virus-like molecular machines that bacteria use to inject toxic proteins into target cells. These systems evolved from bacteriophages, viruses that infect bacteria, but until now scientists did not understand how a single bacterial machine could recognize so many different targets.
“Originally this was a bacteriophage, a virus killing bacteria, that was capable of binding bacterial cells and injecting its DNA,” lead researcher Prof. Asaf Levy of the Faculty of Agriculture, Food and Environment at the Hebrew University of Jerusalem told TPS-IL. “At some point during evolution it turned into a tool that diverse bacteria in different environments use to inject toxin proteins into target cells. The surprise was that there seem to be so many target cells based on our analysis. The average virus tends to be very specific. But here we understand that the eCIS evolved in different microbes to bind extremely different cell types — not only bacteria, but also eukaryotes such as animals, plants, and fungi.”
Researchers had long suspected that eCISs relied on specialized receptor-binding proteins to recognize their targets. But the proteins change so rapidly that standard searches could not detect them.
To solve this, Levy, doctoral researcher Nimrod Nachmias — working with collaborators Zhiren Wang and Xiao Feng from Prof. Peng Jiang’s laboratory at the NHC Key Laboratory of Systems Biology of Pathogens in Beijing — developed a computational algorithm to detect conserved structural elements within the rapidly evolving tail fiber proteins.
By focusing on shared anchor domains that attach proteins to the eCIS particle, they identified thousands of previously hidden receptor-binding proteins. The team catalogued 3,445 distinct tail fiber proteins across 2,585 eCIS gene clusters in 1,069 bacterial and archaeal species — the most comprehensive dataset of its kind.
Each tail fiber has two parts: a conserved region connecting it to the injection system, and a variable region determining which cells it can target. Many of these receptor-binding domains were acquired through horizontal gene transfer, sometimes borrowing DNA from viruses, plants, fungi, and even animal immune components.
“This is accelerated evolution on steroids,” Levy said to TPS-IL. “Bacteria are sampling the biological world for useful binding tools and repurposing them. The tail fiber gene has rapidly evolved through acquiring foreign DNA, recombining it to create new binding specificity, and if beneficial, spreading through horizontal and vertical transfer.”
To demonstrate practical applications, the team engineered an eCIS particle using a tail fiber from a Paenibacillus bacterium resembling hemagglutinin, a receptor-binding protein in influenza and measles viruses. The engineered system successfully bound to and injected proteins into human THP-1 monocyte-like cells while leaving other cell types untouched. Experiments suggested that D-mannose, a sugar on human cell surfaces, may act as a receptor. Electron microscopy captured particles attaching to human cells moments before delivering their cargo.
Levy emphasized the potential applications. “We showed that an engineered eCIS could inject into one human cell type but not others, which is excellent to reduce potential adverse effects,” he told TPS-IL.
The findings open new possibilities by providing a natural, programmable delivery system. Engineered eCIS particles can inject proteins or molecular cargo into specific cell types while leaving others untouched. The catalog of thousands of naturally evolved receptor-binding proteins gives scientists a versatile toolkit for creating custom delivery systems for research, industrial enzymes, or therapeutic molecules.
The study also has applications in agriculture and antimicrobial development. eCIS systems could deliver proteins into crops without genetic modification, enhancing resistance to pests or stress. Bacterial toxins and enzymes carried by eCISs could be repurposed as antimicrobial agents or industrial biocatalysts.
“Bacteria are not limited to slowly adapting their weapons; they can rapidly reinvent them by borrowing binding tools from across the biological world,” Levy told TPS-IL.
The study was published in the peer-reviewed Nature Communications.
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