Using Engineered Gut Bacteria to Prevent Cholera

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Engineered bacteria introduced to the digestive system of lab mice was shown to increase the survival rate of the mice exposed to the cholera bacteria, V. chloerae.

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To investigate the possibility of using commensal bacteria as signal mediators for inhibiting the disease cholera (caused by infection with the marine bacterium V. cholerae), we stably transformed commensal bacteria to express the autoinducer molecule CAI-1 (shown previously to prevent virulence when present with another signaling molecule, AI-2 at high concentrations) and determined the effect on V. cholerae virulence gene expression and infectivity in an infant mouse model. We found that pretreatment of mice for 8 hours with commensal bacteria engineered to express CAI-1 (Nissle-cqsA) greatly increased the mice’s survival (92%) from ingestion of V. cholerae. Pretreatment with Nissle-cqsA for only 4 hours increased survival by 77%, while ingesting Nissle-cqsA at the same time as V. cholerae increased survival rates by 27%. Immuno-staining revealed an 80% reduction in cholera toxin binding to the intestines of mice pretreated for 8 hours with Nissle-cqsA. Further, the numbers of V. cholerae in treated mouse intestines was reduced by 69% after 40 hours. This finding points to an easily administered and inexpensive approach where commensal bacteria are engineered to communicate with invasive species and potentially prevent human disease. Source

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www.cornell.edu