Commensal bacteria as singal mediators within a mammalian host

摘要

Genetically engineered cells and microorganisms are provided for preventing or ameliorating diseases through genetically engineered quorum signaling. Therapeutic methods for using the cells and microorganisms to prevent or ameliorate diseases are also provided. The genetically engineered cells or microorganisms can be engineered to express a signal and used to interrupt the signaling-dependent virulence of an invading pathogen. The cells or microorganisms can be used to provide signal-dependent expression of a desirable gene in order to interrupt, prevent, and/or ameliorate a disease of mammals, such as parasitic diseases, infectious diseases, autoimmune diseases and genetic disorders.

主权项

1. A method of treating diabetes in a mammalian host comprising:
administering to the gastrointestinal tract of mammalian host a recombinant enteric commensal bacterium comprising a recombinant nucleic acid encoding a signal that comprises a mammalian insulin secretion-stimulating peptide glucagon-like peptide 1 (GLP-1), wherein:
the recombinant nucleic acid encoding the signal is under the control of a promoter,the signal is expressed and secreted by the recombinant enteric commensal bacterium in the gastrointestinal tract of the mammalian host, andthe signal stimulates glucose-responsive insulin production in the mammalian host.