Novel Genetically Engineered Probiotics for Targeted Elimination of Pseudomonas aeruginosa in Intestinal Colonization

The intestinal carriage rates of Pseudomonas aeruginosa are notably elevated in immunosuppressed individuals and hospitalized patients, increasing the risk infection antibiotic-associated diarrhea. A potential solution to this issue lies autonomous antibacterial therapy, remaining inactive until a pathogen is detected, releasing compounds on demand eliminate pathogen. This study focuses development genetically engineered probiotics capable detecting eradicating P. by producing secreting PA2-GNU7, aeruginosa-selective antimicrobial peptide (AMP), triggered presence quorum-sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone (3OC12HSL). To achieve goal, plasmid-based systems were constructed produce AMPs response 3OC12HSL secrete them into extracellular medium using either microcin V secretion system or YebF as carrier protein. Following transfer these Escherichia coli Nissle 1917 (EcN), we successfully demonstrated ability EcN express leading inhibition growth vitro. In addition, mouse model colonization, administration resulted reduced levels both feces colon. These findings suggest that holds promise option for combating thus mitigating future endogenous infections vulnerable patients.