Abstract
Trueperella pyogenes (T. pyogenes) is an important opportunistic animal pathogen that causes huge economic losses to the animal husbandry industry. The emergence of bacterial resistance and the unsatisfactory effect of the vaccine have prompted investigators to explore alternative strategies for controlling T. pyogenes infection. Due to the ability of phages to kill multidrug-resistant bacteria, the use of phage therapy to combat multidrug-resistant bacterial infections has attracted attention. In this study, a T. pyogenes phage, vB-ApyS-JF1 (JF1), was isolated from sewage samples, and its whole genome and biological characteristics were elucidated. Moreover, the protective effect of phage JF1 on a mouse bacteremic model caused by T. pyogenes was studied. JF1 harbors a double-stranded DNA genome with a length of 90,130 bp (30.57% G + C). The genome of JF1 lacked bacterial virulence–, antibiotic resistance– and lysogenesis-related genes. Moreover, the genome sequence of JF1 exhibited low coverage (<6%) with all published phages in the NCBI database, and a phylogenetic analysis of the terminase large subunits and capsid indicated that JF1 was evolutionarily distinct from known phages. In addition, JF1 was stable over a wide range of pH values (3 to 11) and temperatures (4 to 50°C) and exhibited strong lytic activity against T. pyogenes in vitro. In murine experiments, a single intraperitoneal administration of JF1 30 min post-inoculation provided 100% protection for mice against T. pyogenes infection. Compared to the phosphate-buffered saline (PBS) treatment group, JF1 significantly (P < 0.01) reduced the bacterial load in the blood and tissues of infected mice. Meanwhile, treatment with phage JF1 relieved the pathological symptoms observed in each tissue. Furthermore, the levels of the inflammatory cytokines tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and interleukin-6 (IL-6) in the blood of infected mice were significantly (P < 0.01) decreased in the phage-treated group. Taken together, these results indicate that phage JF1 demonstrated great potential as an alternative therapeutic treatment against T. pyogenes infection.
Highlights
Trueperella pyogenes (T. pyogenes), previously described as Arcanobacterium pyogenes or Actinomyces pyogenes, is an important opportunistic and prevalent pathogen worldwide (Zhang D. et al, 2017)
BLAST analysis showed that the intergenic spacer region (ISR) and sodA gene sequences of the three strains were 100% identical to those of T. pyogenes strains that were identified in the GenBank database, such as CP050810.1 and CP033904.1, indicating that the isolated strains BS, S4, and Ty belong to T. pyogenes
A total of 15 T. pyogenes colonies were isolated from the blood of three mice infected for 48 h in the phage treatment group, and the results showed that they maintained their sensitivity to phage JF1
Summary
Trueperella pyogenes (T. pyogenes), previously described as Arcanobacterium pyogenes or Actinomyces pyogenes, is an important opportunistic and prevalent pathogen worldwide (Zhang D. et al, 2017). As a zoonotic pathogen, T. pyogenes is responsible for a number of human diseases, such as septicemia, endocarditis, arthritis, endemic leg ulcers, pneumonia, arthritis, various suppurative lesions, and abscesses (Rzewuska et al, 2019). Antibiotics, such as beta-lactams, tetracyclines, and macrolides, have been used to treat liver abscesses caused by T. pyogenes (Jost and Billington, 2005; Zhang D. et al, 2017). Exploiting alternative efficient and safe strategies for controlling T. pyogenes infection is essential
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