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Klebsiella pneumoniae, especially hypervirulent K. pneumoniae (hvKP), is a common opportunistic pathogen that often causes hospital- and community-acquired infections. Capsular polysaccharide (CPS) is an important virulence factor of K. pneumoniae. Some phages encode depolymerases that can recognize and degrade bacterial polysaccharides. In this study, the lytic bacteriophage vB_KpnP_ZK1 (abbreviated as ZK1) was isolated using serotype K1 hvKP as the host. Although amino acid sequence BLAST analysis indicated that the tail fiber protein Depo16 of phage ZK1 showed no significant similarity to any reported phage depolymerases, it displayed enzymatic activities that are characteristic of phage depolymerases. After expression and puri fication, Depo16 could efficiently remove the capsular polysaccharide layer that surrounds the surface of serotype K1 K. pneumoniae. Although no bactericidal activity was detected, Depo16 makes serotype K1 K. pneumoniae sensitive to peritoneal macrophages (PMs). In addition, in a mouse bacteremia model of serotype K1 K. pneumoniae, 25 µg of Depo16 was effective in significantly prolonging survival. Depo16 treatment can reduce the bacterial load in blood and major tissues and alleviate tissue damage in mice. This indicates that the putative depolymerase Depo16 is a potential antibacterial agent against serotype K1 K. pneumoniae infections. IMPORTANCE Klebsiella pneumoniae often causes hospital-acquired infections and community-acquired infections. Capsular polysaccharide (CPS) is one of the crucial virulence factors of K. pneumoniae. K1 and K2 capsular-type K. pneumoniae strains are the most prevalent serotypes of hypervirulent K. pneumoniae (hvKP). In this study, a novel K. pneumoniae phage named vB_KpnP_ZK1 was isolated, and its putative depolymerase Depo16 showed low homology with other reported phage depolymerases. Depo16 can specifically degrade the K. pneumoniae K1 capsule making this serotype sensitive to peritoneal macrophages. More importantly, Depo16 showed a significant therapeutic effect in a mouse bacteremia model caused by serotype K1 K. pneumoniae. Thus, Depo16 is a potential antibacterial agent to combat serotype K1 K. pneumoniae infections. [ABSTRACT FROM AUTHOR]

Salmonella enterica subspecies enterica serovar abortus equi (S. abortus equi) is a frequently reported pathogen causing abortion in mares. In this study, the preventive and therapeutic effects of phage PIZ SAE-01E2 against S. abortus equi in a mouse model of abortion was investigated. Phage PIZ SAE-01E2 was stable at different temperatures (4 ~ 70 °C) and pH values (4 ~ 10) and could lyse the majority of the tested Salmonella strains (25/28) of serotype O:4 and O:9. There is no lysogenic, toxin or antibiotic-resistant related gene in the genome of PIZ SAE-01E2. All of these characteristics indicated PIZ SAE-01E2 has potential for phage therapy. In in vivo experiments, 2 x 103 CFU/mouse of S. abortus equi ATCC 9842 was sufficient to lead to murine abortion (gestational day 14.5) within 48 h. A single dose of intraperitoneal inoculation of PIZ SAE-01E2 (108 PFU/mouse, MOI = 105) 1 h before or after S. abortus equi challenge provided effective protection to all pregnant mice (10/10). The bacterial loads in the placenta and uterus of the infected mice were both significantly decreased (< 102 CFU/g) after 24 h treatment with phage PIZ SAE-01E2 compared to that of control group (> 106 CFU/g). In addition, the levels of inflammatory cytokines in the placenta and blood of the mice in the phage administration groups were significantly reduced (P < 0.05) compared to that of the control group. Altogether, this indicated that PIZ SAE-01E2 showed potential to block abortions induced by S. abortus equi in vivo. [ABSTRACT FROM AUTHOR]