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PNAS 107 (25): 11260-11264

Copyright © 2010 by the National Academy of Sciences.

From the Cover

BIOLOGICAL SCIENCES / APPLIED BIOLOGICAL SCIENCES

Engineered bacterial communication prevents Vibrio cholerae virulence in an infant mouse model

Faping Duan John C. March1

Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY 14853

Edited by Rita R. Colwell, University of Maryland, College Park, MD, and approved May 13, 2010 (received for review February 1, 2010)

Abstract: To investigate the possibility of using commensal bacteria as signal mediators for inhibiting the disease cholera, we stably transformed Escherichia coli Nissle 1917 (Nissle) to express the autoinducer molecule cholera autoinducer 1 (CAI-1) (shown previously to prevent virulence when present with another signaling molecule, autoinducer 2, at high concentrations) and determined the effect on Vibrio cholerae virulence gene expression and colonization in an infant mouse model. We found that pretreatment of mice for 8 h with Nissle 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 h increased survival by 77%, whereas ingesting Nissle-cqsA at the same time as V. cholerae increased survival rates by 27%. Immunostaining revealed an 80% reduction in cholera toxin binding to the intestines of mice pretreated for 8 h with Nissle-cqsA. Further, the numbers of V. cholerae in treated mouse intestines was reduced by 69% after 40 h. 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.

Key Words: quorum sensing • probiotic • signal engineering • prophylactic • enteric disease

Author contributions: F.D. and J.C.M. designed research; F.D. performed research; F.D. and J.C.M. analyzed data; and F.D. and J.C.M. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1001294107/-/DCSupplemental.

1To whom correspondence should be addressed at: Department of Biological and Environmental Engineering, 220 Riley Robb Hall, Ithaca, NY 14853. E-mail: jcm224{at}cornell.edu.

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