Phagemid-based capsid system for CRISPR-Cas13a antimicrobials targeting methicillin-resistant Staphylococcus aureus
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.
Authors
- Priyanka Baranwal (ORCID: https://orcid.org/0000-0002-7866-6748)
- Yusuke Sato’o (ORCID: https://orcid.org/0009-0008-3349-4154)
- Kotaro Kiga (ORCID: https://orcid.org/0000-0002-0248-6951)
- Adeline Yeo Syin Lian
- Teppei Sasahara (ORCID: https://orcid.org/0000-0002-5961-159X)
- Jastin Edrian Cocuangco Revilleza
- Jayathilake Sarangi
- Srivani Veeranarayanan (ORCID: https://orcid.org/0000-0001-5358-5039)
- Mohammad Omar Faruk (ORCID: https://orcid.org/0000-0003-3346-455X)
- Myat Myat Thu
- Yuya Hidaka
- Longzhu Cui (ORCID: https://orcid.org/0000-0002-8909-3885)
- Yi Liu (ORCID: https://orcid.org/0000-0002-4094-2663)
- Huong Minh Nguyen (ORCID: https://orcid.org/0000-0001-5302-2973)
- Yuzuki Shimamori
- Yoshifumi Aiba
- Yutaro Nishikawa
- Ola Alessa
- Xin-Ee Tan (ORCID: https://orcid.org/0000-0001-7847-2583)
- Kanate Thitiananpakorn
- Geoffrey Peterkins Kumwenda (ORCID: https://orcid.org/0000-0001-8687-2296)
- Kazuhiko Miyanaga (ORCID: https://orcid.org/0000-0002-3483-9491)
- Anujin Batbold
- Mahmoud Arbaah
- Shinya Watanabe (ORCID: https://orcid.org/0000-0003-3932-8575)
- Sharmin Sultana (ORCID: https://orcid.org/0000-0002-2687-1280)
- Feng-Yu Li
- Sarah Hossain
- Ho Thi My Duyen
- Takayuki Shimojyo
- Maniruzzaman
- Nayanjin Tergel
- Takashi Sugano
- Tomofumi Kawaguchi
Institutions
- Jichi Medical University (JP)
- National Institute of Infectious Diseases (JP)
- Eiken Chemical (Japan) (JP)
Publication Details
- Journal
- Communications Biology
- Published
- 2024-09-13
- DOI
- https://doi.org/10.1038/s42003-024-06754-w
- Citations
- 12
- Primary Topic
- CRISPR and Genetic Engineering
- Type
- article
- Field-Weighted Citation Impact
- 2.81
Funders
- Jichi Medical University
- Japan Society for the Promotion of Science
- Moonshot Research and Development Program