The Prophage-encoded Hyaluronate Lyase Has Broad Substrate Specificity and Is Regulated by the N-terminal Domain

Abstract

Background: Phage hyaluronate lyases (HLs) of streptococci are intracellular and specifically cleave hyaluronan. Results: HLs completely degrade glycosaminoglycans, have catalytically independent TS␤H domains, and are functional in physiological conditions. Conclusion: Phage HL has a broad glycosaminoglycan degrading activity that is regulated by its own N-terminal region. Significance: Degradation of ECM components by HLs may facilitate the diffusion of toxins etc.

Ability of phages to infect Acinetobacter calcoaceticus‐Acinetobacter baumannii complex species through acquisition of different pectate lyase depolymerase domains

“…Degradation of the bacterial capsules that act as the phage primary receptor enables phages to gain access to the host cell surface to bind irreversibly to a secondary receptor. While some works have studied the interaction of phage-borne depolymerases with Bacillus anthracis, A. baumannii, Pseudomonas putida, Streptococcus equi and Erwinia amylovora (Scorpio et al, 2007;Cornelissen et al, 2012;Singh et al, 2014;Lai et al, 2016), a more in depth research has been done only for phages infecting Klebsiella pneumonia and E. coli (Pelkonen et al, 1992;Stummeyer et al, 2006;Hsu et al, 2013;Lin et al, 2014;Majkowska-Skrobek et al, 2016).…”

Bacteriophage-encoded depolymerases: their diversity and biotechnological applications

“…Many extracellular bacterial hyaluronidases are able to cleave the β-1-4 glycosidic linkage by βelimination and are often suggested to be a virulence factor, by increasing tissue permeability, facilitating the pathogen invasion (Hynes and Walton 2000). The same type of hyaluronidases has been found on some prophages from Streptococcus pyogenes and Streptococcus equi strains (Timoney et al 1982;Hynes et al 1995;Baker et al 2002;Singh et al 2014), and are thought to play a role in phage penetration of streptococcal hyaluronan capsules, facilitating bacterial lysogenization (Singh et al 2014). As no extracellular milieu hyaluronidase activity was detected, these enzymes were suggested to be part of the phage particle to degrade the host's hyaluronic acid capsules, in order to gain access to their surface where phage receptors are located.…”

Presence of Collagen-like Repeats in Bacteriophage–encoded Hyaluronate Lyase

“…According to the crystal structure of HylP2-type HLs, the catalytic domain of the enzyme is significantly far away (~100 Å) from its N-terminal region, so the role of Gly-X-Y collagen motif on the functional activity of the HylP-type HL was least expected. Conversely, Gly-X-Y motif was observed to interact with the calcium ions, as well as showing non-specific interaction with polymeric HA suggesting a non-specific regulatory role of Gly-X-Y motif in HA binding as well as modulating the enzymatic activity of Phage HLs in vitro (Singh et al, 2014a;Singh et al, 2014b).…”

“…such as Streptococcus pyogenes and Streptococcus equi. Phage HLs are class of enzymes that catalyze the degradation of polymeric hyaluronic acid (HA) into a mixture of smaller unsaturated oligosaccharides, reducing ∆HA 10 to ∆HA 2 (HA represents hyaluronic acid) by β-elimination mechanism (Singh et al, 2014a). The enzyme has been reported to have substrate specificity for HA, though it has limited ability to degrade chondroitin 6-sulfate as well as dermatan sulphate (Singh et al, 2014a).…”