Communications Biology (Sep 2024)
Phagemid-based capsid system for CRISPR-Cas13a antimicrobials targeting methicillin-resistant Staphylococcus aureus
- Feng-Yu Li,
- Xin-Ee Tan,
- Yuzuki Shimamori,
- Kotaro Kiga,
- Srivani Veeranarayanan,
- Shinya Watanabe,
- Yutaro Nishikawa,
- Yoshifumi Aiba,
- Yusuke Sato’o,
- Kazuhiko Miyanaga,
- Teppei Sasahara,
- Sarah Hossain,
- Kanate Thitiananpakorn,
- Tomofumi Kawaguchi,
- Huong Minh Nguyen,
- Adeline Yeo Syin Lian,
- Sharmin Sultana,
- Ola Alessa,
- Geoffrey Kumwenda,
- Jayathilake Sarangi,
- Jastin Edrian Cocuangco Revilleza,
- Priyanka Baranwal,
- Mohammad Omar Faruk,
- Yuya Hidaka,
- Myat Thu,
- Mahmoud Arbaah,
- Anujin Batbold,
- Maniruzzaman,
- Yi Liu,
- Ho Thi My Duyen,
- Takashi Sugano,
- Nayanjin Tergel,
- Takayuki Shimojyo,
- Longzhu Cui
Affiliations
- Feng-Yu Li
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Xin-Ee Tan
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Yuzuki Shimamori
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Kotaro Kiga
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Srivani Veeranarayanan
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Shinya Watanabe
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Yutaro Nishikawa
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Yoshifumi Aiba
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Yusuke Sato’o
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Kazuhiko Miyanaga
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Teppei Sasahara
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Sarah Hossain
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Kanate Thitiananpakorn
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Tomofumi Kawaguchi
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Huong Minh Nguyen
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Adeline Yeo Syin Lian
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Sharmin Sultana
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Ola Alessa
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Geoffrey Kumwenda
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Jayathilake Sarangi
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Jastin Edrian Cocuangco Revilleza
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Priyanka Baranwal
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Mohammad Omar Faruk
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Yuya Hidaka
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Myat Thu
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Mahmoud Arbaah
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Anujin Batbold
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Maniruzzaman
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Yi Liu
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Ho Thi My Duyen
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Takashi Sugano
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Nayanjin Tergel
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- Takayuki Shimojyo
- Research Center for Drug and Vaccine Development, National Institute of Infectious Diseases
- Longzhu Cui
- Division of Bacteriology, Department of Infection and Immunity, School of Medicine, Jichi Medical University, Shimotsuke city
- DOI
- https://doi.org/10.1038/s42003-024-06754-w
- Journal volume & issue
-
Vol. 7,
no. 1
pp. 1 – 11
Abstract
Abstract In response to the escalating antibiotic resistance in multidrug-resistant pathogens, we propose an innovative phagemid-based capsid system to generate CRISPR-Cas13a-loaded antibacterial capsids (AB-capsids) for targeted therapy against multidrug-resistant Staphylococcus aureus. Our optimized phagemid system maximizes AB-capsid yield and purity, showing a positive correlation with phagemid copy number. Notably, an 8.65-fold increase in copy number results in a 2.54-fold rise in AB-capsid generation. Phagemids carrying terL-terS-rinA-rinB (prophage-encoded packaging site genes) consistently exhibit high packaging efficiency, and the generation of AB-capsids using lysogenized hosts with terL-terS deletion resulted in comparatively lower level of wild-type phage contamination, with minimal compromise on AB-capsid yield. These generated AB-capsids selectively eliminate S. aureus strains carrying the target gene while sparing non-target strains. In conclusion, our phagemid-based capsid system stands as a promising avenue for developing sequence-specific bactericidal agents, offering a streamlined approach to combat antibiotic-resistant pathogens within the constraints of efficient production and targeted efficacy.
