Stereochemical diversity of AI-2 analogs modulates quorum sensing in Vibrio harveyi and Escherichia coli |
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| Authors: | Rui Fabio Marques João C Miller Stephen T Maycock Christopher D Xavier Karina B Ventura M Rita |
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| Institution: | 1. Instituto de Tecnologia Química e Biológica, Av. da República, Estação Agronómica Nacional, 2780-157 Oeiras, Portugal;2. Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, 2780-156 Oeiras, Portugal;3. Presently at Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Av. Brasília s/n, 1400-038 Lisboa, Portugal;4. Department of Chemistry and Biochemistry, Swarthmore College, Swarthmore, PA 19081, USA;5. Faculdade de Ciências da Universidade de Lisboa, Departamento de Química e Bioquímica, 1749-016 Lisboa, Portugal |
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| 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 (EC(50)=0.65μM) in this organism. Thus, modification at C-5 opens the way to novel methods to manipulate quorum sensing as a method for controlling bacteria. |
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