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Passivating the Background of Living Microbes with a Zwitterionic Peptide for Therapies
Liang Fang1, Simian Cai1, Patrick McMullen1
1Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York 14853, United States.
Abstract:
Living microbial therapies have been proposed as a course of action for a variety of diseases. However, problematic interactions between the host immune system and the microbial organism present significant clinical concerns. Previously, we developed a genetically encoded superhydrophilic zwitterionic peptide, termed EKP, to mimic low-immunogenic zwitterionic materials, which have been used for the chemical modification of biologics such as protein and nucleic acid drugs to increase their in vivo circulation time and reduce their immunogenicity. Herein, we demonstrate the protective effects of the EKP polypeptide genetically cloaking the surface of Saccharomyces cerevisiae as a model microbe in both in vitro and in vivo systems. First, we show that EKP peptide cloaking suppresses the interactions between yeast cells and their specific antibodies, thereby illustrating its cloaking behavior. Then, we examine the in vitro interactions between EKP peptide surface cloaked yeast cells and murine macrophage cells, which exhibit phagocytotic behavior in the presence of foreign microbes. Our results indicate that EKP cloaking suppresses macrophage interactions and thus reduces phagocytosis. Furthermore, EKP cloaked yeast cells demonstrate a prolonged circulation time in mice in vivo.
Insights
Genetically engineered EKP peptide cloaks yeast cells, reducing immune interactions and phagocytosis. This microbial cloaking significantly extends the in vivo circulation time of Saccharomyces cerevisiae.
Area of Science:
- Biotechnology
- Immunology
- Microbiology
Background:
- Living microbial therapies offer therapeutic potential but face challenges due to host immune system interactions.
- Zwitterionic materials are used to modify biologics, enhancing circulation time and reducing immunogenicity.
- A genetically encoded superhydrophilic zwitterionic peptide, EKP, was developed to mimic these low-immunogenic materials.
Purpose of the Study:
- To demonstrate the protective effects of EKP polypeptide genetically cloaking Saccharomyces cerevisiae.
- To evaluate the in vitro and in vivo performance of EKP-cloaked yeast cells.
Main Methods:
- EKP peptide was genetically encoded to cloak the surface of Saccharomyces cerevisiae.
- In vitro studies assessed interactions between EKP-cloaked yeast and specific antibodies, and murine macrophage cells.
- In vivo studies evaluated the circulation time of EKP-cloaked yeast cells in mice.
Main Results:
- EKP cloaking suppressed interactions between yeast cells and specific antibodies.
- EKP cloaking reduced interactions between yeast cells and murine macrophages, decreasing phagocytosis.
- EKP-cloaked yeast cells exhibited prolonged circulation time in vivo.
Conclusions:
- Genetically cloaking yeast with EKP polypeptide effectively reduces immunogenicity and host immune interactions.
- EKP cloaking is a promising strategy to improve the efficacy and safety of microbial therapies.
- This approach has potential applications in developing advanced microbial-based therapeutics.
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