North Carolina State University

University of Virginia Patent Foundation

Evelyn Durmaz

Todd Robert Klaenhammer

Richard Littleton Guerrant

Michael Paul Timko

Cirle Alcantara Warren

Glynis L Kolling

Methods and compositions for targeted delivery of biotherapeutics are provided. The compositions comprise bile-sensitivebacteria modified to release a biotherapeutic agent following bile exposure. Biotherapeutic agents released by thebacteria disclosed herein include AQ and AQR rich peptides. Methods of the invention comprise administering to a subject abacterium modified to release a biotherapeutic agent following bile exposure. Administration of thebacterium promotes a desired therapeutic response. The bacterium may be modified to express and release AQ or AQR rich peptides which subsequently inhibit cellular apoptosis or reduce mucosal damage. Thus, methods of the invention find use in treating or preventing a variety of gastrointestinal disorders includinginfection and antibiotic-associated diarrhea.

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A first aspect of the present invention is an isolated nucleic acid encoding a phage abortive defense protein, the isolated nucleic acid selected from the group consisting of: (a) isolated nucleic acid having the sequence or coding sequence given in SEQ ID NO: 1 (by 'coding sequence' is meant nucleotides 373 to 1668 therein); (b) isolated nucleic acid encoding a phage abortive defense protein and which hybridizes to an nucleic acid having the sequence or coding sequence given in SEQ ID NO: 1, and/or having a sequence at least 60, 70, 80, 90, 92 or 95 percent identical to the sequence or coding sequence given in SEQ ID NO: 1; and (c) isolated nucleic acid encoding a phage abortive defense protein encoded by an isolated nucleic acid of (a) or (b) above, but differing in sequence therefrom due to the degeneracy of the genetic code (e.g., a nucleic acid encoding the protein given in SEQ ID NO: 2).

AbiZ phage resistance gene

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Evelyn Durmaz