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Publication Abstract from PubMed

Capsule polysaccharide is an important virulence factor of Klebsiella pneumoniae (K. pneumoniae), which protects bacteria against the host immune response. A promising therapeutic approach is using phage-derived depolymerases to degrade the capsular polysaccharide and expose and sensitize the bacteria to the host immune system. Here we determined the cryo-electron microscopy (cryo-EM) structures of a bacteriophage tail-spike protein against K. pneumoniae K64, ORF41 (K64-ORF41) and ORF41 in EDTA condition (K64-ORF41(EDTA)), at 2.37 A and 2.50 A resolution, respectively, for the first time. K64-ORF41 exists as a trimer and each protomer contains a beta-helix domain including a right-handed parallel beta-sheet helix fold capped at both ends, an insertion domain, and one beta-sheet jellyroll domain. Moreover, our structural comparison with other depolymerases of K. pneumoniae suggests that the catalytic residues (Tyr528, His574 and Arg628) are highly conserved although the substrate of capsule polysaccharide is variable. Besides that, we figured out the important residues involved in the substrate binding pocket including Arg405, Tyr526, Trp550 and Phe669. This study establishes the structural and functional basis for the promising phage-derived broad-spectrum activity depolymerase therapeutics and effective CPS-degrading agents for the treatment of carbapenem-resistant K. pneumoniae K64 infections.

Structural and functional basis of bacteriophage K64-ORF41 depolymerase for capsular polysaccharide degradation of Klebsiella pneumoniae K64.,Huang T, Zhang Z, Tao X, Shi X, Lin P, Liao D, Ma C, Cai X, Lin W, Jiang X, Luo P, Wu S, Xie Y Int J Biol Macromol. 2024 Apr;265(Pt 2):130917. doi: , 10.1016/j.ijbiomac.2024.130917. Epub 2024 Mar 20. PMID:38513899^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.