Sci. Signal., 29 June 2010
Synthetic Biology Rallying the Commensal Troops
Elizabeth M. Adler
Science Signaling, AAAS, Washington, DC 20005, USA
Individual bacteria secrete signaling molecules sensed by other bacteria, so that bacterial behavior at high population density is frequently different from that at low population density. For instance, Vibrio cholerae, the pathogen that causes cholera, secretes autoinducer 2 (AI-2) and cholera autoinducer 1 (CAI-1), which decrease virulence at high population density by synergistically inhibiting production of cholera toxin and of the toxin coregulated pilus (TCP) that enables bacterial attachment to the intestinal wall. Unlike CAI-1, AI-2 is produced by many bacterial species, including commensal bacteria found in the human gastrointestinal tract. Duan and March transformed the commensal bacterium Escherichia coli Nissle 1917 (Nissle), which produces AI-2, with the gene encoding the final CAI-1 synthetic enzyme so that the engineered bacteria (Nissle-csqA) produced CAI-1 in amounts comparable to those of V. cholerae. Two- to three-day-old mice were protected against cholera by ingestion of Nissle-csqA but not by unmodified Nissle. Whereas no mice survived V. cholerae ingestion without ingesting Nissle-csqA, 92% of those prefed 109 Nissle-csqA 8 hours before ingesting V. cholerae were alive 48 hours after V. cholerae exposure, as were 77% of those prefed 109 Nissle-csqA hours before exposure and 27% of those given 109 Nissle-csqA concurrently with V. cholerae. Analyses of mouse intestinal tracts revealed comparable numbers of V. cholerae in mice prefed Nissle-csqA to those prefed Nissle or given no pretreatment 16 hours after V. cholerae ingestion but substantially decreased numbers 40 hours after infection. Moreover, immunohistochemical analysis revealed decreased cholera toxin in the GI tracts of the Nissle-csqA–treated mice. The authors conclude that engineering commensal bacteria to signal to V. cholerae could provide one approach to protect against cholera in humans.
Citation: E. M. Adler, Rallying the Commensal Troops. Sci. Signal. 3, ec193 (2010).
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