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

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

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.669618

DOI=10.3389/fmicb.2021.669618

ISSN=1664-302X

ABSTRACT=<p>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 <italic>Klebsiella pneumoniae</italic> with K23 capsule type. The phages belonged to the <italic>Autographiviridae</italic> (vB_KpnP_Dlv622) and <italic>Myoviridae</italic> (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 <italic>K. pneumoniae</italic> with capsule type K23 and were able to protect <italic>Galleria mellonella</italic> larvae in a model infection with a <italic>K. pneumoniae</italic> 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.</p>