Rationale redesign of type III secretion systems: toward the development of non-pathogenic E. coli for in vivo delivery of therapeutic payloads.

Transkingdom secretion systems that bacteria use to inject proteins directly into the cytosol of mammalian host cells play an essential role in the virulence of many Gram-negative bacterial pathogens. Current efforts are underway to repurpose these machines as novel therapeutics; type III secretion systems as vectors for the delivery of proteins of therapeutic value including heterologous antigens for vaccine development and type IV secretion systems as vectors for DNA. While initial studies focused on the use of attenuated or replication incompetent pathogens, the recent development of non-pathogenic Escherichia coli that encode programmable type III secretion systems expands possibilities for the in vivo directed delivery of therapeutic payloads.