Pathogenic bacteria are becoming increasingly resistant to antibiotics. Alternatives must be found and validated to avoid falling back into the pre-antibiotic era. The use of bacteriophages, natural enemies of bacteria, is one of the most promising alternatives, both in agriculture/veterinary medicine and in human health. 60% of known phages consist of a capsid protecting the viral DNA and a long flexible tail, which serves to recognise the host via one or more receptor binding proteins (RBPs) located at the tip of the tail. The RBP-receptor interaction triggers infection: opening of the capsid, perforation of the bacterial wall and injection of viral DNA into the host cytoplasm.
In this study, IBS researchers studied the infection of E. coli with bacteriophage T5. This infection is initiated by the irreversible binding of the T5 RBP protein pb5 to its bacterial receptor, the outer membrane transporter FhuA. Thanks to spectacular instrumental advances in electron microscopy, they were able to determine, at atomic resolution, the structure of T5 tail tip before and after interaction with FhuA reconstituted in a membrane patch. These structures allowed them to understand how host recognition triggers the infection process, and to detail the molecular mechanisms involved in the different steps, from the interaction between the RBP and its receptor, to the perforation of the host’s outer membrane, via the opening of the phage tail and its anchoring to the membrane. These studies will contribute a better control and use of these fascinating nanomachines.
Structural basis of bacteriophage T5 infection trigger and E. coli cell wall perforation. Linares R, Arnaud C-A, Effantin G, Darnault C, Epalle NH, Erba EB, Schoehn G, Breyton C. Science Advances; 9(12):eade9674
Deciphering Bacteriophage T5 Host Recognition Mechanism and Infection Trigger. Degroux S, Effantin G, Linares R, Schoehn G, Breyton C. Journal of Virology; 97(3):e0158422
Contact : Cécile Breyton (IBS/Membrane and Pathogens Group)