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

• Published in: International journal of molecular sciences Vol. 23; no. 20; p. 12146
• Main Authors: Taslem Mourosi, Jarin, Awe, Ayobami, Guo, Wenzheng, Batra, Himanshu, Ganesh, Harrish, Wu, Xiaorong, Zhu, Jingen
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12-10-2022; MDPI
• Subjects: Adsorption; Amino acids; Anti-Bacterial Agents; Antibacterial agents; Antiinfectives and antibacterials; Bacteria; bacteriophage (phage); Bacteriophages - physiology; Carrier Proteins; Drug resistance; E coli; Fibers; Genomes; Host range; Host Specificity; Molecular modelling; Pathogens; Phages; phage–host interaction; Proteins; Receptor mechanisms; Review; Structure-function relationships; T4 phage; tail fiber; tail fiber engineering; Tail fiber protein; tail fiber structure; Virion; phage host range; phage–host interaction; tail fiber; bacteriophage (phage); T4 phage; tail fiber engineering; tail fiber structure; machine learning
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232012146

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
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.