4.7 Article

Biological properties of Staphylococcus virus ΦSA012 for phage therapy

Journal

SCIENTIFIC REPORTS
Volume 12, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41598-022-25352-6

Keywords

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Funding

  1. MEXT/JSPS KAKENHI [JP17H01506, JP19K15985]
  2. Japan Agency for Medical Research and Development (AMED) [JP21fk0108497, JP21fk0108496, JP22wm0325022, JP21gm1610002, JP20fk0108134, JP21gm1610002s0102, JP22fk0108134s0303]

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The study assessed the biological stability and clinical potential of Staphylococcus virus Phi SA012. The virus showed a wide host range and efficient lytic activity. Experiments on mice demonstrated the ability of Phi SA012 to spread and accumulate in specific organs without causing inflammation. Additionally, the study highlighted the importance of appropriate dosing and administration periods for effective phage therapy.
Staphylococcus virus Phi SA012 has a wide host range and efficient lytic activity. Here, we assessed the biological stability of Phi SA012 against temperature, freeze-thawing, and pH to clinically apply the phage. In addition, inoculation of Phi SA012 through i.p. and i.v. injections into mice revealed that phages were reached the limit of detection in serum and accumulated notably spleens without inflammation at 48 h post-inoculation. Furthermore, inoculation of Phi SA012 through s.c. injections in mice significantly induced IgG, which possesses neutralizing activity against Phi SA012 and other Staphylococcus viruses, Phi SA039 and Phi MR003, but not Pseudomonas viruses Phi S12-3 and Phi R18 or Escherichia viruses T1, T4, and T7 in vitro. Immunoelectron microscopic analysis showed that purified anti-phage IgG recognizes the long-tail fiber of staphylococcus viruses. Although S. aureus inoculation resulted in a 25% survival rate in a mouse i.p. model, Phi SA012 inoculation (i.p.) improved the survival rate to 75%; however, the survival rate of Phi SA012-immunized mice decreased to less than non-immunized mice with phage i.v. injection at a MOI of 100. These results indicated that Phi SA012 possesses promise for use against staphylococcal infections but we should carefully address the appropriate dose and periods of phage administration. Our findings facilitate understandings of staphylococcus viruses for phage therapy.

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