Understanding Bacteriophage Tail Fiber Interaction with Host Surface Receptor: The Key Blueprint for Reprogramming Phage Host Range

Bacteriophages (phages), as natural antibacterial agents, are being rediscovered because of the growing threat of multi- and pan-drug-resistant bacterial pathogens globally. However, with an estimated 10(31) phages on the planet, finding the right phage to recognize a specific bacterial host is like looking for a needle in a trillion haystacks. The host range of a phage is primarily determined by phage tail fibers (or spikes), which initially mediate reversible and specific recognition and adsorption by susceptible bacteria. Recent significant advances at single-molecule and atomic levels have begun to unravel the structural organization of tail fibers and underlying mechanisms of phage-host interactions. Here, we discuss the molecular mechanisms and models of the tail fibers of the well-characterized T4 phage's interaction with host surface receptors. Structure-function knowledge of tail fibers will pave the way for reprogramming phage host range and will bring future benefits through more-effective phage therapy in medicine. Furthermore, the design strategies of tail fiber engineering are briefly summarized, including machine-learning-assisted engineering inspired by the increasingly enormous amount of phage genetic information.

Automated summary

Bacteriophages are being rediscovered as natural antibacterial agents due to the increasing threat of drug-resistant bacterial pathogens. Understanding the structure and function of phage tail fibers is crucial for reprogramming phages' host range and improving phage therapy. Design strategies, including machine-learning-assisted engineering, are being developed based on the vast amount of phage genetic information available.