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A Pro-Drug Approach for Selective Modulation of AI-2-Mediated Bacterial Cell-to-Cell Communication
Department of Chemistry and Biochemistry, University of Maryland, Building 091, College Park, MD 20742, USA
* Author to whom correspondence should be addressed.
Received: 29 December 2011; in revised form: 26 February 2012 / Accepted: 15 March 2012 / Published: 21 March 2012
Abstract: The universal quorum sensing autoinducer, AI-2, is utilized by several bacteria. Analogs of AI-2 have the potential to modulate bacterial behavior. Selectively quenching the communication of a few bacteria, in the presence of several others in an ecosystem, using analogs of AI-2 is non-trivial due to the ubiquity of AI-2 processing receptors in many bacteria that co-exist. Herein, we demonstrate that when an AI-2 analog, isobutyl DPD (which has been previously shown to be a quorum sensing, QS, quencher in both Escherichia coli and Salmonella typhimurium) is modified with ester groups, which get hydrolyzed once inside the bacterial cells, only QS in E. coli, but not in S. typhimurium, is inhibited. The origin of this differential QS inhibition could be due to differences in analog permeation of the bacterial membranes or ester hydrolysis rates. Such differences could be utilized to selectively target QS in specific bacteria amongst a consortium of other species that also use AI-2 signaling.
Keywords: AI-2; DPD analog; quorum sensing inhibitor; ester pro-drug; lsr expression; autoinducer cell permeation; autoinducer processing; enteric bacteria
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Guo, M.; Gamby, S.; Nakayama, S.; Smith, J.; Sintim, H.O. A Pro-Drug Approach for Selective Modulation of AI-2-Mediated Bacterial Cell-to-Cell Communication. Sensors 2012, 12, 3762-3772.
Guo M, Gamby S, Nakayama S, Smith J, Sintim HO. A Pro-Drug Approach for Selective Modulation of AI-2-Mediated Bacterial Cell-to-Cell Communication. Sensors. 2012; 12(3):3762-3772.
Guo, Min; Gamby, Sonja; Nakayama, Shizuka; Smith, Jacqueline; Sintim, Herman O. 2012. "A Pro-Drug Approach for Selective Modulation of AI-2-Mediated Bacterial Cell-to-Cell Communication." Sensors 12, no. 3: 3762-3772.