Phages Targeting Flagella: Adsorption and Infection Mechanisms of Flagellotropic Phages

Bacteriophages (phages) are viruses that exclusively infect bacteria. They adsorb to their hosts through binding to cell receptors including flagella, pili, or lipopolysaccharide (LPS). Adsorption is a two-step process, with reversible adhesion to cell surface receptors followed by irreversible binding. Many phages and all known flagellotropic phages belong to the class Caudoviricetes, which encompasses tailed phages with double-stranded DNA genomes. Most flagellotropic phages adsorb reversibly to the flagella of their host and traverse the flagellum to reach the cell surface. Next, secondary receptors, such as LPS or pili portals, may then mediate irreversible binding and DNA ejection. Because flagellar motility is an important virulence factor in many bacterial pathogens, flagellotropic phages could be useful to treat or prevent bacterial infections or contaminations. For a broader application, host-range expansion techniques can be applied. The Appelmans protocol, which involves passaging multiple, closely related phages through successive cultures of susceptible and nonsusceptible bacteria, relies on recombination and spontaneous mutations to generate chimeric phages. These newly evolved phages with a broadened host range are promising candidates for phage therapy. A better understanding of flagellotropic phage infection mechanisms and their host-range expansion might lead to the successful use of flagellotropic phages as therapeutics.