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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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Thiazolidinediones and dioxazaborocanes synthesized by Brackman et al. [124] and tested as QS inhibitors in V. harveyi.
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f15-ijms-14-17694: Thiazolidinediones and dioxazaborocanes synthesized by Brackman et al. [124] and tested as QS inhibitors in V. harveyi.

Mentions: Brackman and co-workers designed and evaluated two libraries of compounds (thiazolidinediones and dioxazaborocanes) for anti-QS activities. The authors suggested that the thiazolidinediones (such as 115, 117 and 118, see Figure 15) are structural mimics of brominated furanones, such as 117 and 118, and hence, could potentially act on biomolecular targets that furanones are known to target, such as LuxS. Also, the dioxazaborocanes (119–123) resemble boronated AI-2 (see Figure 15) [124,125]. A few of them (119–121) acted as potent AI-2 QS inhibitors against V. harveyi, with EC50 at low micromolar level (see Figure 15 for EC50 values).


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)

Thiazolidinediones and dioxazaborocanes synthesized by Brackman et al. [124] and tested as QS inhibitors in V. harveyi.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f15-ijms-14-17694: Thiazolidinediones and dioxazaborocanes synthesized by Brackman et al. [124] and tested as QS inhibitors in V. harveyi.
Mentions: Brackman and co-workers designed and evaluated two libraries of compounds (thiazolidinediones and dioxazaborocanes) for anti-QS activities. The authors suggested that the thiazolidinediones (such as 115, 117 and 118, see Figure 15) are structural mimics of brominated furanones, such as 117 and 118, and hence, could potentially act on biomolecular targets that furanones are known to target, such as LuxS. Also, the dioxazaborocanes (119–123) resemble boronated AI-2 (see Figure 15) [124,125]. A few of them (119–121) acted as potent AI-2 QS inhibitors against V. harveyi, with EC50 at low micromolar level (see Figure 15 for EC50 values).

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