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Small molecule inhibitors of AI-2 signaling in bacteria: state-of-the-art and future perspectives for anti-quorum sensing agents.

Guo M, Gamby S, Zheng Y, Sintim HO - Int J Mol Sci (2013)

Bottom Line: These molecules, called autoinducers, are classified as intraspecies (i.e., molecules produced and perceived by the same bacterial species) or interspecies (molecules that are produced and sensed between different bacterial species).Additionally, these molecules have the potential to be used in synthetic biology applications whereby these small molecules are used as inputs to switch on and off AI-2 receptors.In this review, we highlight the state-of-the-art in the development of small molecules that perturb AI-2 signaling in bacteria and offer our perspective on the future development and applications of these classes of molecules.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of Maryland, Building 091, College Park, MD 20742, USA.

ABSTRACT
Bacteria respond to different small molecules that are produced by other neighboring bacteria. These molecules, called autoinducers, are classified as intraspecies (i.e., molecules produced and perceived by the same bacterial species) or interspecies (molecules that are produced and sensed between different bacterial species). AI-2 has been proposed as an interspecies autoinducer and has been shown to regulate different bacterial physiology as well as affect virulence factor production and biofilm formation in some bacteria, including bacteria of clinical relevance. Several groups have embarked on the development of small molecules that could be used to perturb AI-2 signaling in bacteria, with the ultimate goal that these molecules could be used to inhibit bacterial virulence and biofilm formation. Additionally, these molecules have the potential to be used in synthetic biology applications whereby these small molecules are used as inputs to switch on and off AI-2 receptors. In this review, we highlight the state-of-the-art in the development of small molecules that perturb AI-2 signaling in bacteria and offer our perspective on the future development and applications of these classes of molecules.

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Acetate-protected AI-2 synthesized by Doutheau and co-workers. (a) Structure of bis-(O)-acetylated-DPD; (b) Bioluminescence induction in V. harveyi, (S)-170 (●) and (S)-DPD 11(■); (c) β-gal production in S. typhimurium, (S)-170 (●) and (S)-DPD 11(■); (d) Biofilm inhibition in B. cereus, (S)-170 (●) and (S)-DPD 11 (■) at 8 μM; (Adapted from [138] with permission. Copyright 2007, Elsevier).
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f24-ijms-14-17694: Acetate-protected AI-2 synthesized by Doutheau and co-workers. (a) Structure of bis-(O)-acetylated-DPD; (b) Bioluminescence induction in V. harveyi, (S)-170 (●) and (S)-DPD 11(■); (c) β-gal production in S. typhimurium, (S)-170 (●) and (S)-DPD 11(■); (d) Biofilm inhibition in B. cereus, (S)-170 (●) and (S)-DPD 11 (■) at 8 μM; (Adapted from [138] with permission. Copyright 2007, Elsevier).

Mentions: Both AI-2 and analogs have issues with stability and to address the potential instability of AI-2 analogs [61], Doutheau and co-workers demonstrated that acetate protected analogs of AI-2 were as effective as natural AI-2 but had the added advantage of being stable (see Figure 24).


Small molecule inhibitors of AI-2 signaling in bacteria: state-of-the-art and future perspectives for anti-quorum sensing agents.

Guo M, Gamby S, Zheng Y, Sintim HO - Int J Mol Sci (2013)

Acetate-protected AI-2 synthesized by Doutheau and co-workers. (a) Structure of bis-(O)-acetylated-DPD; (b) Bioluminescence induction in V. harveyi, (S)-170 (●) and (S)-DPD 11(■); (c) β-gal production in S. typhimurium, (S)-170 (●) and (S)-DPD 11(■); (d) Biofilm inhibition in B. cereus, (S)-170 (●) and (S)-DPD 11 (■) at 8 μM; (Adapted from [138] with permission. Copyright 2007, Elsevier).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3794749&req=5

f24-ijms-14-17694: Acetate-protected AI-2 synthesized by Doutheau and co-workers. (a) Structure of bis-(O)-acetylated-DPD; (b) Bioluminescence induction in V. harveyi, (S)-170 (●) and (S)-DPD 11(■); (c) β-gal production in S. typhimurium, (S)-170 (●) and (S)-DPD 11(■); (d) Biofilm inhibition in B. cereus, (S)-170 (●) and (S)-DPD 11 (■) at 8 μM; (Adapted from [138] with permission. Copyright 2007, Elsevier).
Mentions: Both AI-2 and analogs have issues with stability and to address the potential instability of AI-2 analogs [61], Doutheau and co-workers demonstrated that acetate protected analogs of AI-2 were as effective as natural AI-2 but had the added advantage of being stable (see Figure 24).

Bottom Line: These molecules, called autoinducers, are classified as intraspecies (i.e., molecules produced and perceived by the same bacterial species) or interspecies (molecules that are produced and sensed between different bacterial species).Additionally, these molecules have the potential to be used in synthetic biology applications whereby these small molecules are used as inputs to switch on and off AI-2 receptors.In this review, we highlight the state-of-the-art in the development of small molecules that perturb AI-2 signaling in bacteria and offer our perspective on the future development and applications of these classes of molecules.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of Maryland, Building 091, College Park, MD 20742, USA.

ABSTRACT
Bacteria respond to different small molecules that are produced by other neighboring bacteria. These molecules, called autoinducers, are classified as intraspecies (i.e., molecules produced and perceived by the same bacterial species) or interspecies (molecules that are produced and sensed between different bacterial species). AI-2 has been proposed as an interspecies autoinducer and has been shown to regulate different bacterial physiology as well as affect virulence factor production and biofilm formation in some bacteria, including bacteria of clinical relevance. Several groups have embarked on the development of small molecules that could be used to perturb AI-2 signaling in bacteria, with the ultimate goal that these molecules could be used to inhibit bacterial virulence and biofilm formation. Additionally, these molecules have the potential to be used in synthetic biology applications whereby these small molecules are used as inputs to switch on and off AI-2 receptors. In this review, we highlight the state-of-the-art in the development of small molecules that perturb AI-2 signaling in bacteria and offer our perspective on the future development and applications of these classes of molecules.

Show MeSH