Details

Autor(en) / Beteiligte

• Volozhantsev, Nikolay V.
• Borzilov, Alexander I.
• Shpirt, Anna M.
• Krasilnikova, Valentina M.
• Verevkin, Vladimir V.
• Denisenko, Egor A.
• Kombarova, Tatyana I.
• Shashkov, Alexander S.
• Knirel, Yuriy A.
• Dyatlov, Ivan A.

Titel

Comparison of the therapeutic potential of bacteriophage KpV74 and phage-derived depolymerase (β-glucosidase) against Klebsiella pneumoniae capsular type K2

Ist Teil von

• Virus research, 2022-12, Vol.322, p.198951, Article 198951

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2022

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• •A bacteriophage specific to hypermucoviscous K2 type K. pneumoniae was characterized•Phage depolymerase has been identified as a β-glucosidase•In the mouse model, depolymerase efficiency exceeds phage efficiency•During in vivo experiments, phage resistance mutants of K. pneumoniae were isolated•A single base deletion in the wzx gene reduces K. pneumoniae virulence. Bacteriophages and phage polysaccharide-degrading enzymes (depolymerases) are garnering attention as possible alternatives to antibiotics. Here, we describe the antimicrobial properties of bacteriophage KpV74 and phage depolymerase Dep_kpv74 specific to the hypervirulent Klebsiella pneumoniae of the K2 capsular type. The depolymerase Dep_kpv74 was identified as a specific glucosidase that cleaved the K2 type capsular polysaccharides of the K. pneumoniae by a hydrolytic mechanism. This depolymerase was effective against thigh soft tissue K. pneumoniae infection in mice without inducing adverse behavioral effects or toxicity. The depolymerase efficiency was similar to or greater than the bacteriophage efficiency. The phage KpV74 had a therapeutic effect only for treating the infection caused by the phage-propagating K. pneumoniae strain and was completely inactive against the infection caused by the K. pneumoniae strain that did not support phage multiplication. The depolymerase was effective in both cases. A mutant resistant to phage and depolymerase was isolated during the treatment of mice with bacteriophage. A confirmed one-base deletion in the flippase-coding wzx gene of this mutant is assumed to affect the polysaccharide capsule, abolishing the KpV74 phage adsorption and reducing the K. pneumoniae virulence.