Abstract
Clostridioides difficile is the single most significant cause of hospital-acquired infections in the US with 500,000 infections per year, characterised by inflammation, diarrhea, bowel perforation and potential death. The predominant treatment for C. difficile infection is antibiotic prescription which disrupts the gut microbiome and exacerbates resistance concerns. Our solution is to engineer a Lactobacillus reuteri probiotic chassis to detect the quorum signaling autoinducing peptide of C. difficile in the intestinal lumen. Detection uses the C. difficile two component signaling system, to induce secretion of a C. difficile-specific endolysin to cleave its cell wall and leave the remaining intestinal flora intact. Monte Carlo simulations were performed to analyse the population dynamics of both species and refine our system within the spatial constraints of the human gut topology. Our design offers a targeted therapeutic for C. difficile infection, opening the possibility of a new modular system to treat gastrointestinal bacterial infection.
