A work led by researchers from the Higher Council for Scientific Research ( CSIC ) has revealed the atomic structure of the protein complex used by the T7 bacteriophage virus to pierce the bacterial wall and replicate inside ‘Escherichia coli’, one of the most problematic resistant bacteria to first-line antibiotics.
The finding, published in the scientific journal ‘ Proceedings of the National Academy of Sciences ‘, opens the door to the development of new therapies against bacterial resistance , which causes many infections contracted in hospitals.
According to data from the World Health Organization ( WHO ), if measures are not taken, by 2050 there will be 10 million annual deaths caused by microorganisms resistant to antibiotics. One of the newest alternatives to alleviate this problem is to use viruses called bacteriophages or phages as drugs that infect bacteria and kill them.
By joining the bacteria, the virus introduces its genetic material and multiplies, generating new phages that can infect others and lead to a chain reaction that kills the pathogen.
“Bacteriophages represent an extreme case of optimization of the infectious process. Due to the complexity and resistance of bacterial cells , these viruses need to pierce not only the cell membrane, but also the outer wall of the bacteria to form a channel that crosses space intermediate (periplasm) and serves to transport the viral genome into the bacterial cytoplasm.
In fact, bacteriophage T7 has a very special infection machinery that it transiently builds in situ during the infection process “, details Ana Cuervo, a researcher who he leads the work together with José López Carrascosa, both researchers from the Department of Macromolecules of the National Center for Biotechnology (CNB-CSIC) “.
Using electronic cryomicroscopy techniques, the researchers have been able to characterize two different stages of assembly that serve to pierce the wall of the bacterium ‘E. coli ‘. The entry complex is formed from viral proteins present in the envelope of the virus (capsid), whose function and structure change transiently.
“We have observed a complex of proteins (called core) that are normally inside the capsid with the viral DNA wound around it like a coil. After anchoring the virus to the surface of the bacteria, this complex is disassembled and the proteins that form it are They direct towards the contact zone of the virus and the bacteria, where they build a kind of extensible tail, with a completely different conformation that has new functions: on the one hand, it forms a channel in the periplasm of the bacteria and, on the other, its activity enzymatic degradation of the components of the bacterial wall of ‘E. coli’.
In this way, the DNA of the virus enters the bacteria safely and infection occurs “, explains Mar Pérez-Ruiz, also a researcher at the CNB-CSIC.
This achievement opens the way to the development of new alternative therapies to conventional antibiotics. “Thanks to the ability of these proteins to pierce the E.coli membrane, it would be possible to think of the complex as a new antibacterial tool with biomedical applications,” concludes López Carrascosa.
