The structure was elucidated in this paper NCBI PubMed ID:33113762 Publication DOI:10.3390/antibiotics9110732 Journal NLM ID:101637404 Publisher: Basel, Switzerland: MDPI AG Correspondence: nikvolobolensk.org Institutions: N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Moscow, Russia, State Research Center for Applied Microbiology and Biotechnology, 142279 Obolensk, Moscow Region, Russia
Bacteriophages and phage enzymes are considered as possible alternatives to antibiotics in the treatment of infections caused by antibiotic-resistant bacteria. Due to the ability to cleave the capsular polysaccharides (CPS), one of the main virulence factors of Klebsiella pneumoniae, phage depolymerases, has potential in the treatment of K. pneumoniae infections. Here, we characterized in vivo two novel phage-encoded polysaccharide depolymerases as therapeutics against clinical isolates of K. pneumoniae. The depolymerases Dep_kpv79 and Dep_kpv767 encoded by Klebsiella phages KpV79 (Myoviridae; Jedunavirus) and KpV767 (Autographiviridae, Studiervirinae, Przondovirus), respectively, were identified as specific beta-galactosidases that cleave the K. pneumoniae K57 type CPS by the hydrolytic mechanism. They were found to be highly effective at combating sepsis and hip infection caused by K. pneumoniae in lethal mouse models. Here, 80-100% of animals were protected against death by a single dose (e.g., 50 ?g/mouse) of the enzyme injected 0.5 h after infection by K. pneumoniae strains of the K57 capsular type. The therapeutic effect of the depolymerases is because they strip the capsule and expose the underlying bacterium to the immune attack such as complement-mediated killing. These data provide one more confirmation that phage polysaccharide depolymerases represent a promising tool for antimicrobial therapy.
Methods: 13C NMR, 1H NMR, NMR-2D, PCR, DNA techniques, GPC, enzymatic depolymerization, function analysis of gene clusters, HR-ESI-MS, phage characterization Comments, role: oligosaccharide 2 was obtained by cleavage of the CPS with the depolymerases Dep_kpv79 and Dep_kpv767 encoded by Klebsiella phages KpV79.
Related record ID(s): 7638, 32226 NCBI Taxonomy refs (TaxIDs):573 Reference(s) to other database(s): GTC:G53252UN Show glycosyltransferases
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