Journal
PHARMACEUTICS
Volume 14, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/pharmaceutics14091916
Keywords
Klebsiella pneumoniae; phage; depolymerase; capsule; biofilm; anti-virulence agent
Categories
Funding
- National Natural Science Foundation of China [31870989]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) [KYCX21_3280]
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A new temperate phage vB_KpnP_ZX1 was isolated, which showed efficient capsule degradation activity through its encoded depolymerase Dep_ZX1. In vitro experiments demonstrated that purified Dep_ZX1 was effective in preventing biofilm formation, degrading formed biofilms, and increasing the susceptibility of bacteria to antibiotics. Animal experiments also showed that Dep_ZX1 protected infected mice from death. Therefore, Dep_ZX1 is a promising anti-virulence agent for K57-type Klebsiella pneumoniae infection or biofilm diseases.
A novel temperate phage vB_KpnP_ZX1 was isolated from hospital sewage samples using the clinically derived K57-type Klebsiella pneumoniae as a host. Phage vB_KpnP_ZX1, encoding three lysogen genes, the repressor, anti-repressor, and integrase, is the fourth phage of the genus Uetakevirus, family Podoviridae, ever discovered. Phage vB_KpnP_ZX1 did not show ideal bactericidal effect on K. pneumoniae 111-2, but TEM showed that the depolymerase Dep_ZX1 encoded on the short tail fiber protein has efficient capsule degradation activity. In vitro antibacterial results show that purified recombinant Dep_ZX1 can significantly prevent the formation of biofilm, degrade the formed biofilm, and improve the sensitivity of the bacteria in the biofilm to the antibiotics kanamycin, gentamicin, and streptomycin. Furthermore, the results of animal experiments show that 50 mu g Dep_ZX1 can protect all K. pneumoniae 111-2-infected mice from death, whereas the control mice infected with the same dose of K. pneumoniae 111-2 all died. The degradation activity of Dep_ZX1 on capsular polysaccharide makes the bacteria weaken their resistance to immune cells, such as complement-mediated serum killing and phagocytosis, which are the key factors for its therapeutic action. In conclusion, Dep_ZX1 is a promising anti-virulence agent for the K57-type K. pneumoniae infection or biofilm diseases.
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