Researchers from Skoltech (half of the VEB.RF Group) have uncovered the molecular mechanisms that make one of essentially the most persistent laboratory contaminants — bacteriophage T1 — unusually resilient and harmful to bacterial cultures.
The findings might add extra to the reason of the character of contamination in microbiological laboratories and biotech manufacturing services, and in addition supply a protecting answer: the use of a resistant bacterial pressure that may be applied in laboratory observe instantly. The work was printed within the International Journal of Molecular Sciences and supported by Russian Science Foundation grants.
Bacteriophages — viruses that kill micro organism — are indispensable in biotechnology and medication, however in laboratories they typically trigger appreciable issues. For instance, T1 household phages can survive for years on gear, go by filters, and destroy a whole bacterial tradition in a single day, disrupting an experiment or manufacturing run. They are troublesome to get rid of even with harsh sterilization strategies. For a very long time, it remained unclear which particular genes and proteins confer such resilience.
A analysis staff led by Artem Isaev, the top of the Laboratory for Metagenome Analysis on the Skoltech Biomed Technologies Center and a recipient of the Russian Federation Presidential Prize in Science and Innovation for Young Scientists in 2025, remoted a brand new phage from river water in Kaliningrad, naming it KanT1 after Immanuel Kant. It was discovered to contaminate a variety of E. coli strains, together with these utilized in laboratories, and to be immune to many disinfection strategies.
“We discovered that KanT1 was constantly contaminating our samples, and this became the starting point for a systematic study of its genome. To better understand how to fight this ‘enemy,’ we decided to try to determine what makes this virus so resilient,” mentioned Artem Isaev. “It turned out that standard annotation methods, which compare genes based on sequence, were failing to identify many important proteins in these phages — we managed to detect them and predict their functions through protein structure analysis.”
A key novelty of the work was the use of protein construction prediction strategies. Using AlphaFold3 — an AI-based system for predicting protein buildings — the scientists had been capable of characterize the features of proteins beforehand thought-about hypothetical, which account for almost half of the genome. The authors found a protein with a selected construction — the so-called SH3 area.
Previously, such buildings had solely been present in viruses that infect micro organism with thick, sturdy cell partitions — so-called Gram-positive micro organism. This is the primary time such a protein has been present in a virus of E. coli, which has a skinny cell wall. It is situated close to a bunch of genes accountable for destroying the bacterial cell from inside to launch new viral particles.
“Finding an SH3 domain in a phage that infects a Gram-negative bacterium came as a surprise to us. We hypothesize that the SH3 protein helps the phage more efficiently destroy the cell from within, which may explain its aggressiveness and ability to spread rapidly through a culture,” mentioned Arina Eremina, one of the lead authors of the research, an undergraduate scholar at HSE University finishing her mission on the Laboratory for Metagenome Analysis on the Skoltech Biomed Technologies Center.
Comparative evaluation of 522 genomes of associated phages confirmed that the SH3 area is discovered in additional than a 3rd of them, however is much from common. This suggests its position as a further evolutionary instrument that phages can purchase to boost their effectivity. The authors additionally refined the perform of one other key mechanism — superinfection exclusion — which permits the virus to “take over” a cell and block reinfection by different phages.
“Our study demonstrates that even such a well-studied object as phage T1 contains a significant number of yet uncharacterized genes. The use of protein structure prediction methods allowed us to penetrate this ‘dark matter’ of the viral genome and identify functionally significant components. In the long term, understanding such mechanisms will aid in the development of new phage-based antibacterial agents,” shared Polina Iarema, one of the lead authors of the research, a PhD scholar at Skoltech within the Life Sciences program.
The work explains why T1-like phages contaminate laboratory cultures and presents an answer to the issue. The researchers discovered that the E. coli HS pressure — a bacterium usually discovered within the human intestine — is totally resistant to those viruses. This implies that in laboratories the place contaminating phages are significantly problematic, this pressure can be utilized as a substitute of strains delicate to phage contamination.
Reference: Eremina A, Iarema P, Kotovskaya O, et al. Analysis of a novel T1-like phage KanT1 reveals a standalone SH3 area as a widespread element of Drexlerviridae cell lysis module. IJMS. 2026;27(9):3756. doi: 10.3390/ijms27093756
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