Probiotics in a Gram-Negative Organism

Use of Engineered Bacteria as Probiotic Therapeutics

Our plan is to turn the Type 6 Secretion System (T6SS)/Tse2 from Pseudomonas aeruginosa into a targeted antibiotic suitable for use in E. coli. The T6SS is a 22 protein complex found in many gram-negative species ( including P. aeruginosa, but not E. coli). The T6SS acts much like a spear, physically puncturing the cell membrane of the target cell and providing a channel through which proteins can be secreted. In P. aeruginosa, one of the major substrates of the T6SS is the toxic protein Tse2 (Type Six Excreted 2). Normally, Tse2 forms a complex with Tsi2 ( Type Six Immunity 2), a protein co-expressed with Tse2 that acts as an antitoxin. Before secrfetion of Tse2, Tsi2 dissociates from Tse2. Tse2 is then secreted into the target cell by the T6SS, killing the target cell. One of the goals of this projedct is to regulate

Type VI Secretion

Inducing Tse2/Tsi2 Circuit