Bacteriophage-encoded virion-associated enzymes to overcome the carbohydrate barriers during the infection process

Abstract

Bacteriophages are bacterial viruses that infect the host after successful receptor recognition and adsorption to the cell surface. The irreversible adherence followed by genome material ejection into host cell cytoplasm must be preceded by the passage of diverse carbohydrate barriers such as capsule polysaccharides (CPSs), O-polysaccharide chains of lipopolysaccharide (LPS) molecules, extracellular polysaccharides (EPSs) forming biofilm matrix, and peptidoglycan (PG) layers. For that purpose, bacteriophages are equipped with various virion-associated carbohydrate active enzymes, termed polysaccharide depolymerases and lysins, that recognize, bind, and degrade the polysaccharide compounds. We discuss the existing diversity in structural locations, variable architectures, enzymatic specificities, and evolutionary aspects of polysaccharide depolymerases and virion-associated lysins (VALs) and illustrate how these aspects can correlate with the host spectrum. In addition, we present methods that can be used for activity determination and the application potential of these enzymes as antibacterials, antivirulence agents, and diagnostic tools.

Characterization of a novel Yersinia ruckeri serotype O1‐specific bacteriophage with virulence‐neutralizing activity

“…The depressed halo plaque morphology observed for φNC10 has been reported previously in bacteriophages that produce polysaccharide depolymerase activity during the infection process [for a review, see Latka et al, ]. This activity is associated with tail fibres or tailspikes and can be both virion‐associated and freely soluble (Bessler, Fehmel, Freund‐Molbert, Knufermann, & Stirm, ).…”

“…Some bacteriophages encode depolymerases capable of degrading bacterial exopolysaccharides such as LPS and capsular polysaccharides. These polysaccharide depolymerases are virion‐associated, and highly specific enzymes thought to aid in bacteriophage penetration of bacterial polysaccharide layers (Latka, Maciejewska, Majkowska‐Skrobek, Briers, & Drulis‐Kawa, ). Polysaccharide depolymerases are currently being developed as novel virulence‐neutralizing agents capable of removing protective surface polysaccharides leaving pathogens exposed to host immune factors.…”

K. pneumoniaeST258 genomic variability and bacteriophage susceptibility

“…JIPh_Kp122 and JIPh_Kp127 also showed broader spectra beyond capsular type, but lysed ST258 isolates overall with poor efficiency, with evidence of abortive or passive lysis (53), perhaps limiting their therapeutic value. Capsule-targeting bacteriophages have been shown to be effective against K. pneumoniae of different capsular type in vitro and in vivo , along with depolymerases, which are enzymes produced by phages that cleave glycosidic bonds disrupting capsule integrity (54,55). Depolymerase activity was originally shown to be random, however recent work demonstrated depolymerase specificity toward certain K types (56,57), an indication that enzymatic degradation may be causing the patterns of lytic activity observed in our study.…”

Social Bacteriophages

“…Important pathogenic enterobacteria such as Acinetobacter baumannii, Escherichia coli, and Klebsiella pneumoniae produce EPS capsules. Phage depolymerases, which are required for infecting these bacteria, are usually anchored to spike or tail fiber proteins of the phage virion, albeit some are secreted as soluble diffusible proteins [21]. The latter may be considered as an extracellular public good, whereas anchored depolymerases could be viewed as privatized goods, but they might also be shareable in two ways.…”

“…These tails could diffuse locally and digest EPS capsules for the benefit of other members of the population. Lysins [21], which degrade bacterial cell walls, could also potentially function as public goods, similarly to depolymerases.…”