Stereochemical Diversity Of AI-2 Analogs Modulates Quorum Sensing In Vibrio Harveyi And Escherichia Coli
Bioorganic And Medicinal Chemistry
Bacteria coordinate population-dependent behaviors such as virulence by intra-and inter-species communication (quorum sensing). Autoinducer-2 (AI-2) regulates inter-species quorum sensing. AI-2 derives from the spontaneous cyclisation of linear (S)-4,5-dihydroxypentanedione (DPD) into two isomeric forms in dynamic equilibrium. Different species of bacteria have different classes of AI-2 receptors (LsrB and LuxP) which bind to different cyclic forms. In the present work, DPD analogs with a new stereocenter at C-5 (4,5-dihydroxyhexanediones (DHDs)) have been synthesized and their biological activity tested in two bacteria. (4S, 5R)-DHD is a synergistic agonist in Escherichia coli (which contains the LsrB receptor), while it is an agonist in Vibrio harveyi (LuxP), displaying the strongest agonistic activity reported so far (EC50 = 0.65 mu M) in this organism. Thus, modification at C-5 opens the way to novel methods to manipulate quorum sensing as a method for controlling bacteria. (C) 2011 Elsevier Ltd. All rights reserved.
F. Rui, J. C. Marques, Stephen T. Miller, C. D. Maycock, K. B. Xavier, and M. R. Ventura.
"Stereochemical Diversity Of AI-2 Analogs Modulates Quorum Sensing In Vibrio Harveyi And Escherichia Coli".
Bioorganic And Medicinal Chemistry.