Biological properties of Staphylococcus virus ΦSA012 for phage therapy

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 revea...

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Main Authors: Jumpei Fujiki, Tomohiro Nakamura, Keisuke Nakamura, Keita Nishida, Yurika Amano, Yusaku Watanabe, Satoshi Gondaira, Masaru Usui, Masaru Shimizu, Kazuhiko Miyanaga, Shinya Watanabe, Tomohito Iwasaki, Kotaro Kiga, Tomoko Hanawa, Hidetoshi Higuchi, Teiji Sawa, Yasunori Tanji, Yutaka Tamura, Longzhu Cui, Hidetomo Iwano
Format: Article
Language:English
Published: Nature Portfolio 2022-12-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-022-25352-6
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author Jumpei Fujiki
Tomohiro Nakamura
Keisuke Nakamura
Keita Nishida
Yurika Amano
Yusaku Watanabe
Satoshi Gondaira
Masaru Usui
Masaru Shimizu
Kazuhiko Miyanaga
Shinya Watanabe
Tomohito Iwasaki
Kotaro Kiga
Tomoko Hanawa
Hidetoshi Higuchi
Teiji Sawa
Yasunori Tanji
Yutaka Tamura
Longzhu Cui
Hidetomo Iwano
author_facet Jumpei Fujiki
Tomohiro Nakamura
Keisuke Nakamura
Keita Nishida
Yurika Amano
Yusaku Watanabe
Satoshi Gondaira
Masaru Usui
Masaru Shimizu
Kazuhiko Miyanaga
Shinya Watanabe
Tomohito Iwasaki
Kotaro Kiga
Tomoko Hanawa
Hidetoshi Higuchi
Teiji Sawa
Yasunori Tanji
Yutaka Tamura
Longzhu Cui
Hidetomo Iwano
author_sort Jumpei Fujiki
collection DOAJ
description 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 Staphylococcus viruses, ΦSA039 and ΦMR003, but not Pseudomonas viruses ΦS12-3 and ΦR18 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, ΦSA012 inoculation (i.p.) improved the survival rate to 75%; 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.
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spelling doaj.art-6f8f05107af54089ad955e98197452652022-12-22T04:18:47ZengNature PortfolioScientific Reports2045-23222022-12-0112111510.1038/s41598-022-25352-6Biological properties of Staphylococcus virus ΦSA012 for phage therapyJumpei Fujiki0Tomohiro Nakamura1Keisuke Nakamura2Keita Nishida3Yurika Amano4Yusaku Watanabe5Satoshi Gondaira6Masaru Usui7Masaru Shimizu8Kazuhiko Miyanaga9Shinya Watanabe10Tomohito Iwasaki11Kotaro Kiga12Tomoko Hanawa13Hidetoshi Higuchi14Teiji Sawa15Yasunori Tanji16Yutaka Tamura17Longzhu Cui18Hidetomo Iwano19Laboratory of Veterinary Biochemistry, Rakuno Gakuen University School of Veterinary MedicineLaboratory of Veterinary Biochemistry, Rakuno Gakuen University School of Veterinary MedicineLaboratory of Veterinary Biochemistry, Rakuno Gakuen University School of Veterinary MedicineLaboratory of Veterinary Biochemistry, Rakuno Gakuen University School of Veterinary MedicineLaboratory of Veterinary Biochemistry, Rakuno Gakuen University School of Veterinary MedicineLaboratory of Veterinary Biochemistry, Rakuno Gakuen University School of Veterinary MedicineLaboratory of Animal Health, Rakuno Gakuen University School of Veterinary MedicineLaboratory of Food Microbiology and Food Safety, Rakuno Gakuen University School of Veterinary MedicineDepartment of Anesthesiology, Kyoto Prefectural University of MedicineDivision of Bacteriology, Department of Infection and Immunology, School of Medicine, Jichi Medical UniversityDivision of Bacteriology, Department of Infection and Immunology, School of Medicine, Jichi Medical UniversityDepartment of Food Science and Human Wellness, College of Agriculture, Food and Environment Science, Rakuno Gakuen UniversityResearch Center for Drug and Vaccine Development, National Institute of Infectious DiseasesDepartment of Infectious Diseases, Kyorin University School of MedicineLaboratory of Animal Health, Rakuno Gakuen University School of Veterinary MedicineDepartment of Anesthesiology, Kyoto Prefectural University of MedicinePhage Therapy Institute, Waseda UniversityLaboratory of Food Microbiology and Food Safety, Rakuno Gakuen University School of Veterinary MedicineDivision of Bacteriology, Department of Infection and Immunology, School of Medicine, Jichi Medical UniversityLaboratory of Veterinary Biochemistry, Rakuno Gakuen University School of Veterinary MedicineAbstract 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 Staphylococcus viruses, ΦSA039 and ΦMR003, but not Pseudomonas viruses ΦS12-3 and ΦR18 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, ΦSA012 inoculation (i.p.) improved the survival rate to 75%; 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.https://doi.org/10.1038/s41598-022-25352-6
spellingShingle Jumpei Fujiki
Tomohiro Nakamura
Keisuke Nakamura
Keita Nishida
Yurika Amano
Yusaku Watanabe
Satoshi Gondaira
Masaru Usui
Masaru Shimizu
Kazuhiko Miyanaga
Shinya Watanabe
Tomohito Iwasaki
Kotaro Kiga
Tomoko Hanawa
Hidetoshi Higuchi
Teiji Sawa
Yasunori Tanji
Yutaka Tamura
Longzhu Cui
Hidetomo Iwano
Biological properties of Staphylococcus virus ΦSA012 for phage therapy
Scientific Reports
title Biological properties of Staphylococcus virus ΦSA012 for phage therapy
title_full Biological properties of Staphylococcus virus ΦSA012 for phage therapy
title_fullStr Biological properties of Staphylococcus virus ΦSA012 for phage therapy
title_full_unstemmed Biological properties of Staphylococcus virus ΦSA012 for phage therapy
title_short Biological properties of Staphylococcus virus ΦSA012 for phage therapy
title_sort biological properties of staphylococcus virus φsa012 for phage therapy
url https://doi.org/10.1038/s41598-022-25352-6
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