Biological nanofactories target and activate epithelial cell surfaces for modulating bacterial quorum sensing and interspecies signaling.

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TitleBiological nanofactories target and activate epithelial cell surfaces for modulating bacterial quorum sensing and interspecies signaling.
Publication TypeJournal Article
Year of Publication2010
AuthorsHebert, CG, Gupta, A, Fernandes, R, Tsao, C-Y, Valdes, JJ, Bentley, WE
JournalACS Nano
Volume4
Issue11
Pagination6923-31
Date Published2010 Nov 23
ISSN1936-086X
KeywordsCaco-2 Cells, Coculture Techniques, Dipeptidyl Peptidase 4, Epithelial Cells, Escherichia coli, Homoserine, Humans, Immunoglobulin G, Lactones, Nanotechnology, Quorum Sensing, Recombinant Fusion Proteins, Vibrio
Abstract

In order to control the behavior of bacteria present at the surface of human epithelial cells, we have created a biological "nanofactory" construct that "coats" the epithelial cells and "activates" the surface to produce the bacterial quorum sensing signaling molecule, autoinducer-2 (AI-2). Specifically, we demonstrate directed modulation of signaling among Escherichia coli cells grown over the surface of human epithelial (Caco-2) cells through site-directed attachment of biological nanofactories. These "factories" comprise a fusion protein expressed and purified from E. coli containing two AI-2 bacterial synthases (Pfs and LuxS), a protein G IgG binding domain, and affinity ligands for purification. The final factory is fabricated ex vivo by incubating with an anti-CD26 antibody that binds the fusion protein and specifically targets the CD26 dipeptidyl peptidase found on the outer surface of Caco-2 cells. This is the first report of the intentional "in vitro" synthesis of bacterial autoinducers at the surface of epithelial cells for the redirection of quorum sensing behaviors of bacteria. We envision tools such as this will be useful for interrogating, interpreting, and disrupting signaling events associated with the microbiome localized in human intestine and other environments.

DOI10.1021/nn1013066
Alternate JournalACS Nano
PubMed ID21028779