Secretion of functional interferon by the type 3 secretion system of enteropathogenic Escherichia coli

Abstract

BackgroundType I interferons (IFN-I)—a group of cytokines with immunomodulatory, antiproliferative, and antiviral properties—are widely used as therapeutics for various cancers and viral diseases. Since IFNs are proteins, they are highly susceptible to degradation by proteases and by hydrolysis in the strong acid environment of the stomach, and they are therefore administered parenterally. In this study, we examined whether the intestinal bacterium, enteropathogenic Escherichia coli (EPEC), can be exploited for oral delivery of IFN-Is. EPEC survives the harsh conditions of the stomach and, upon reaching the small intestine, expresses a type III secretion system (T3SS) that is used to translocate effector proteins across the bacterial envelope into the eukaryotic host cells.ResultsIn this study, we developed an attenuated EPEC strain that cannot colonize the host but can secrete functional human IFNα2 variant through the T3SS. We found that this bacteria-secreted IFN exhibited antiproliferative and antiviral activities similar to commercially available IFN.ConclusionThese findings present a potential novel approach for the oral delivery of IFN via secreting bacteria.