AUTHOR=Li Ping , Zhang Yangheng , Yan Fuhua , Zhou Xin 

TITLE=Characteristics of a Bacteriophage, vB_Kox_ZX8, Isolated From Clinical Klebsiella oxytoca and Its Therapeutic Effect on Mice Bacteremia

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.763136

DOI=10.3389/fmicb.2021.763136

ISSN=1664-302X

ABSTRACT=<p><italic>Klebsiella oxytoca</italic> is an important nosocomial and community-acquired opportunistic pathogenic <italic>Klebsiella</italic> and has become the second most prevalent strain in the clinic after <italic>K. pneumoniae</italic>. However, there have been few reports of bacteriophages used for treating <italic>K. oxytoca</italic>. In this study, a novel bacteriophage, vB_Kox_ZX8, which specifically infects <italic>K. oxytoca</italic> AD3, was isolated for the first time from human fecal samples. The biological characteristics of vB_Kox_ZX8 showed an incubation period of 10 min, a burst size of 74 PFU/cell, and a stable <italic>pH</italic> range of 3–11. Genomic bioinformatics studies of vB_Kox_ZX8 showed that it belongs to the genus <italic>Przondovirus</italic>, subfamily <italic>Studiervirinae</italic>, family <italic>Autographiviridae</italic>. The genome of vB_Kox_ZX8 is 39,398 bp in length and contains 46 putative open reading frames encoding functional proteins, such as DNA degradation, packaging, structural, lysin-holin, and hypothetical proteins. We further investigated the efficacy of vB_Kox_ZX8 phage in the treatment of mice with bacteremia caused by <italic>K. oxytoca</italic> infection. The results showed that vB_Kox_ZX8 (5 × 10<sup>9</sup> PFU/mouse) injected intraperitoneally alone was metabolized rapidly in BALB/c mice, and no significant side effects were observed in the control and treatment groups. Importantly, intraperitoneal injection with a single dose of phage vB_Kox_ZX8 (5 × 10<sup>7</sup> PFU/mouse) for 1 h post-infection saved 100% of BALB/c mice from bacteremia induced by intraperitoneal challenge with a minimum lethal dose of <italic>K. oxytoca</italic> AD3. However, all negative control mice injected with PBS alone died. Owing to its good safety, narrow host infectivity, high lysis efficiency <italic>in vitro</italic>, and good <italic>in vivo</italic> therapeutic effect, phage vB_Kox_ZX8 has the potential to be an excellent antibacterial agent for clinical <italic>K. oxytoca</italic>-caused infections.</p>