Novel Klebsiella pneumoniae K23-Specific Bacteriophages From Different Families: Similarity of Depolymerases and Their Therapeutic Potential

Roman B Gorodnichev; Nikolay V Volozhantsev; Valentina M Krasilnikova; Ivan N Bodoev; Maria A Kornienko; Nikita S Kuptsov; Anastasia V Popova; Galina I Makarenko; Alexander I Manolov; Pavel V Slukin; Dmitry A Bespiatykh; Vladimir V Verevkin; Egor A Denisenko; Eugene E Kulikov; Vladimir A Veselovsky; Maja V Malakhova; Ivan A Dyatlov; Elena N Ilina; Egor A Shitikov

doi:10.3389/fmicb.2021.669618

Novel Klebsiella pneumoniae K23-Specific Bacteriophages From Different Families: Similarity of Depolymerases and Their Therapeutic Potential

Front Microbiol. 2021 Aug 9:12:669618. doi: 10.3389/fmicb.2021.669618. eCollection 2021.

Authors

Roman B Gorodnichev¹, Nikolay V Volozhantsev², Valentina M Krasilnikova², Ivan N Bodoev¹, Maria A Kornienko¹, Nikita S Kuptsov¹, Anastasia V Popova², Galina I Makarenko¹, Alexander I Manolov¹, Pavel V Slukin², Dmitry A Bespiatykh¹, Vladimir V Verevkin², Egor A Denisenko², Eugene E Kulikov³, Vladimir A Veselovsky¹, Maja V Malakhova¹, Ivan A Dyatlov², Elena N Ilina¹, Egor A Shitikov¹

Affiliations

¹ Department of Molecular Biology and Genetics, Federal Research and Clinical Center of Physical-Chemical Medicine, Moscow, Russia.
² Department of Molecular Microbiology, State Research Center for Applied Microbiology and Biotechnology, Moscow, Russia.
³ Research Center of Biotechnology of the Russian Academy of Sciences, Winogradsky Institute of Microbiology, Moscow, Russia.

Abstract

Antibiotic resistance is a major public health concern in many countries worldwide. The rapid spread of multidrug-resistant (MDR) bacteria is the main driving force for the development of novel non-antibiotic antimicrobials as a therapeutic alternative. Here, we isolated and characterized three virulent bacteriophages that specifically infect and lyse MDR Klebsiella pneumoniae with K23 capsule type. The phages belonged to the Autographiviridae (vB_KpnP_Dlv622) and Myoviridae (vB_KpnM_Seu621, KpS8) families and contained highly similar receptor-binding proteins (RBPs) with polysaccharide depolymerase enzymatic activity. Based on phylogenetic analysis, a similar pattern was also noted for five other groups of depolymerases, specific against capsule types K1, K30/K69, K57, K63, and KN2. The resulting recombinant depolymerases Dep622 (phage vB_KpnP_Dlv622) and DepS8 (phage KpS8) demonstrated narrow specificity against K. pneumoniae with capsule type K23 and were able to protect Galleria mellonella larvae in a model infection with a K. pneumoniae multidrug-resistant strain. These findings expand our knowledge of the diversity of phage depolymerases and provide further evidence that bacteriophages and phage polysaccharide depolymerases represent a promising tool for antimicrobial therapy.

Keywords: Galleria mellonella; Klebsiella pneumoniae; bacteriophage; capsular type; capsule depolymerase; multidrug-resistance.

Copyright © 2021 Gorodnichev, Volozhantsev, Krasilnikova, Bodoev, Kornienko, Kuptsov, Popova, Makarenko, Manolov, Slukin, Bespiatykh, Verevkin, Denisenko, Kulikov, Veselovsky, Malakhova, Dyatlov, Ilina and Shitikov.