Related Experiment Video
Updated: May 24, 2025
08:39
Electroporation of Functional Bacterial Effectors into Mammalian Cells
Published on: January 19, 2015
10.0K
Engineering non-pathogenic bacteria for auto-transporter-driven secretion of functional interferon.
May Tfilin Samuel1, Irina Rostovsky1, Alona Kuzmina1
1The Shraga Segal Department of Microbiology, Immunology, and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Gut Microbes
|March 3, 2025
Summary
Researchers engineered bacteria to deliver protein drugs orally using the EspC secretion system. This novel biologic delivery platform successfully secreted interferon-alpha (IFNα), demonstrating potential for effective gastrointestinal tract (GIT) therapeutics.
Area of Science:
- Biotechnology
- Microbiology
- Drug Delivery Systems
Background:
- Oral administration of protein therapeutics (biologics) is challenging due to gastrointestinal tract (GIT) degradation.
- Bacteria offer a potential solution as robust delivery vehicles capable of surviving the GIT.
- The type 5 secretion system (T5SS) is a bacterial mechanism for secreting proteins.
Purpose of the Study:
- To investigate bacteria as a delivery vehicle for biologics.
- To explore the use of the EspC T5SS for secreting therapeutic proteins under simulated gut conditions.
- To evaluate the efficacy of EspC-mediated secretion of interferon-alpha (IFNα).
Main Methods:
- Engineered nonpathogenic bacteria to express the EspC T5SS from enteropathogenic *Escherichia coli*.
- Investigated the secretion of an interferon-alpha (IFNα) variant using the EspC system.
- Assessed the biological activity of the secreted IFNα in cell-based assays, including JAK-STAT pathway activation and antiviral response.
Main Results:
- Successfully demonstrated that EspC facilitates the secretion of an IFNα variant in nonpathogenic bacteria.
- The EspC-secreted IFNα retained biological activity, activating the JAK-STAT pathway.
- The secreted IFNα upregulated IFN-stimulated genes and induced a significant antiviral response in cells.
Conclusions:
- The EspC protein from *E. coli* serves as a viable platform for delivering protein-based therapeutics.
- This bacterial secretion system offers a novel approach to overcome challenges in oral biologic drug delivery.
- The findings provide proof of concept for using engineered bacteria and T5SS for therapeutic protein delivery.
