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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
Frontiers in microbiology, 08/2021, Letnik: 12Journal Article
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 with K23 capsule type. The phages belonged to the (vB_KpnP_Dlv622) and (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 with capsule type K23 and were able to protect larvae in a model infection with a 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.
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