Harnessing a T1 Phage-Derived Spanin for Developing Phage-Based Antimicrobial Development
The global increase in the prevalence of drug-resistant bacteria has necessitated the development of alternative treatments that do not rely on conventional antimicrobial agents. Using bacteriophage-derived lytic enzymes in antibacterial therapy shows promise; however, a thorough comparison and eval...
Main Authors: | , , , , , , , , , , , , |
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Format: | Article |
Language: | English |
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American Association for the Advancement of Science (AAAS)
2024-01-01
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Series: | BioDesign Research |
Online Access: | https://spj.science.org/doi/10.34133/bdr.0028 |
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author | Wakana Yamashita Shinjiro Ojima Azumi Tamura Aa Haeruman Azam Kohei Kondo Zhang Yuancheng Longzhu Cui Masaki Shintani Masato Suzuki Yoshimasa Takahashi Koichi Watashi Satoshi Tsuneda Kotaro Kiga |
author_facet | Wakana Yamashita Shinjiro Ojima Azumi Tamura Aa Haeruman Azam Kohei Kondo Zhang Yuancheng Longzhu Cui Masaki Shintani Masato Suzuki Yoshimasa Takahashi Koichi Watashi Satoshi Tsuneda Kotaro Kiga |
author_sort | Wakana Yamashita |
collection | DOAJ |
description | The global increase in the prevalence of drug-resistant bacteria has necessitated the development of alternative treatments that do not rely on conventional antimicrobial agents. Using bacteriophage-derived lytic enzymes in antibacterial therapy shows promise; however, a thorough comparison and evaluation of their bactericidal efficacy are lacking. This study aimed to compare and investigate the bactericidal activity and spectrum of such lytic enzymes, with the goal of harnessing them for antibacterial therapy. First, we examined the bactericidal activity of spanins, endolysins, and holins derived from 2 Escherichia coli model phages, T1 and T7. Among these, T1-spanin exhibited the highest bactericidal activity against E. coli. Subsequently, we expressed T1-spanin within bacterial cells and assessed its bactericidal activity. T1-spanin showed potent bactericidal activity against all clinical isolates tested, including bacterial strains of 111 E. coli, 2 Acinetobacter spp., 3 Klebsiella spp., and 3 Pseudomonas aeruginosa. In contrast, T1 phage-derived endolysin showed bactericidal activity against E. coli and P. aeruginosa, yet its efficacy against other bacteria was inferior to that of T1-spanin. Finally, we developed a phage-based technology to introduce the T1-spanin gene into target bacteria. The synthesized non-proliferative phage exhibited strong antibacterial activity against the targeted bacteria. The potent bactericidal activity exhibited by spanins, combined with the novel phage synthetic technology, holds promise for the development of innovative antimicrobial agents. |
first_indexed | 2024-04-24T21:45:13Z |
format | Article |
id | doaj.art-e6648894c7274c73982c6f8070c4657f |
institution | Directory Open Access Journal |
issn | 2693-1257 |
language | English |
last_indexed | 2024-04-24T21:45:13Z |
publishDate | 2024-01-01 |
publisher | American Association for the Advancement of Science (AAAS) |
record_format | Article |
series | BioDesign Research |
spelling | doaj.art-e6648894c7274c73982c6f8070c4657f2024-03-21T03:25:50ZengAmerican Association for the Advancement of Science (AAAS)BioDesign Research2693-12572024-01-01610.34133/bdr.0028Harnessing a T1 Phage-Derived Spanin for Developing Phage-Based Antimicrobial DevelopmentWakana Yamashita0Shinjiro Ojima1Azumi Tamura2Aa Haeruman Azam3Kohei Kondo4Zhang Yuancheng5Longzhu Cui6Masaki Shintani7Masato Suzuki8Yoshimasa Takahashi9Koichi Watashi10Satoshi Tsuneda11Kotaro Kiga12Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke-shi, Tochigi 329-0498, Japan.Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke-shi, Tochigi 329-0498, Japan.Department of Engineering, Graduate School of Integrated Science and Technology, Shizuoka University, 3-5-1 Johoku, Naka-ku, Hamamatsu, Shizuoka, 432-8561, Japan.Antimicrobial Resistance Research Center, National Institute of Infectious Diseases, Tokyo, Japan.Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.Department of Life Science and Medical Bioscience, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan.Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases, Tokyo 162-8640, Japan.The global increase in the prevalence of drug-resistant bacteria has necessitated the development of alternative treatments that do not rely on conventional antimicrobial agents. Using bacteriophage-derived lytic enzymes in antibacterial therapy shows promise; however, a thorough comparison and evaluation of their bactericidal efficacy are lacking. This study aimed to compare and investigate the bactericidal activity and spectrum of such lytic enzymes, with the goal of harnessing them for antibacterial therapy. First, we examined the bactericidal activity of spanins, endolysins, and holins derived from 2 Escherichia coli model phages, T1 and T7. Among these, T1-spanin exhibited the highest bactericidal activity against E. coli. Subsequently, we expressed T1-spanin within bacterial cells and assessed its bactericidal activity. T1-spanin showed potent bactericidal activity against all clinical isolates tested, including bacterial strains of 111 E. coli, 2 Acinetobacter spp., 3 Klebsiella spp., and 3 Pseudomonas aeruginosa. In contrast, T1 phage-derived endolysin showed bactericidal activity against E. coli and P. aeruginosa, yet its efficacy against other bacteria was inferior to that of T1-spanin. Finally, we developed a phage-based technology to introduce the T1-spanin gene into target bacteria. The synthesized non-proliferative phage exhibited strong antibacterial activity against the targeted bacteria. The potent bactericidal activity exhibited by spanins, combined with the novel phage synthetic technology, holds promise for the development of innovative antimicrobial agents.https://spj.science.org/doi/10.34133/bdr.0028 |
spellingShingle | Wakana Yamashita Shinjiro Ojima Azumi Tamura Aa Haeruman Azam Kohei Kondo Zhang Yuancheng Longzhu Cui Masaki Shintani Masato Suzuki Yoshimasa Takahashi Koichi Watashi Satoshi Tsuneda Kotaro Kiga Harnessing a T1 Phage-Derived Spanin for Developing Phage-Based Antimicrobial Development BioDesign Research |
title | Harnessing a T1 Phage-Derived Spanin for Developing Phage-Based Antimicrobial Development |
title_full | Harnessing a T1 Phage-Derived Spanin for Developing Phage-Based Antimicrobial Development |
title_fullStr | Harnessing a T1 Phage-Derived Spanin for Developing Phage-Based Antimicrobial Development |
title_full_unstemmed | Harnessing a T1 Phage-Derived Spanin for Developing Phage-Based Antimicrobial Development |
title_short | Harnessing a T1 Phage-Derived Spanin for Developing Phage-Based Antimicrobial Development |
title_sort | harnessing a t1 phage derived spanin for developing phage based antimicrobial development |
url | https://spj.science.org/doi/10.34133/bdr.0028 |
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