Stereochemical Diversity Of AI-2 Analogs Modulates Quorum Sensing In Vibrio Harveyi And Escherichia Coli

Document Type

Article

Publication Date

1-1-2012

Published In

Bioorganic And Medicinal Chemistry

Abstract

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.

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