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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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(a) Generation of d-ribulose-5-phosohate in the OPP pathway; (b) Degradation pathway of Ru5P to form 4,5-dihydroxy-2,3-dipentadione and HMF.
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f28-ijms-14-17694: (a) Generation of d-ribulose-5-phosohate in the OPP pathway; (b) Degradation pathway of Ru5P to form 4,5-dihydroxy-2,3-dipentadione and HMF.

Mentions: Another pathway to AI-2, which does not involve the activated methyl cycle, has also been proposed. It has been shown that in the presence of acid, both DPD and 4-hydroxy-5-methyl-3(2H)-furanone (HMF, 33) spontaneously form from d-ribulose-5-phosphate (Ru5P, 26) (Scheme 2b) [54]. MHF has been shown to have moderate effects on bioluminescence in V. harveyi [50]. Ru5P is formed during the catabolism of glucose via the oxidative pentose phosphate (OPP) pathway (Scheme 2a).


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)

(a) Generation of d-ribulose-5-phosohate in the OPP pathway; (b) Degradation pathway of Ru5P to form 4,5-dihydroxy-2,3-dipentadione and HMF.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f28-ijms-14-17694: (a) Generation of d-ribulose-5-phosohate in the OPP pathway; (b) Degradation pathway of Ru5P to form 4,5-dihydroxy-2,3-dipentadione and HMF.
Mentions: Another pathway to AI-2, which does not involve the activated methyl cycle, has also been proposed. It has been shown that in the presence of acid, both DPD and 4-hydroxy-5-methyl-3(2H)-furanone (HMF, 33) spontaneously form from d-ribulose-5-phosphate (Ru5P, 26) (Scheme 2b) [54]. MHF has been shown to have moderate effects on bioluminescence in V. harveyi [50]. Ru5P is formed during the catabolism of glucose via the oxidative pentose phosphate (OPP) pathway (Scheme 2a).

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