Biological properties of Staphylococcus virus ΦSA012 for phage therapy

Author:

Fujiki Jumpei1,Nakamura Tomohiro1,Nakamura Keisuke1,Nishida Keita1,Amano Yurika1,Watanabe Yusaku1,Gondaira Satoshi1,Usui Masaru1,Shimizu Masaru2,Miyanaga Kazuhiko3,Watanabe Shinya3,Iwasaki Tomohito4,Kiga Kotaro5,Hanawa Tomoko6,Higuchi Hidetoshi1,Sawa Teiji2,Tanji Yasunori7,Tamura Yutaka1,Cui Longzhu3,Iwano Hidetomo1

Affiliation:

1. Rakuno Gakuen University School of Veterinary Medicine

2. Kyoto Prefectural University of Medicine

3. Jichi Medical University

4. Rakuno Gakuen University

5. National Institute of Infectious Disease

6. Kyorin University School of Medicine

7. Waseda University

Abstract

Abstract Staphylococcus virus ΦSA012 has a wide host range and efficient lytic activity. Here, we assessed the biological stability of ΦSA012 against temperature, freeze-thawing, and pH to clinically apply the phage. In addition, inoculation of ΦSA012 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 ΦSA012 through s.c. injections in mice significantly induced IgG, which possesses neutralizing activity against ΦSA012 and other Staphylococcusviruses, ΦSA039 and ΦMR003, but not Pseudomonasviruses ΦS12-3 and ΦR18 or Escherichiaviruses 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, ΦSA012 inoculation (i.p.) improved the survival rate to 70%; however, the survival rate of ΦSA012-immunized mice decreased to less than non-immunized mice with phage i.v. injection at a MOI of 100. These results indicated that ΦSA012 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.

Publisher

Research Square Platform LLC

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