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A pro-drug approach for selective modulation of AI-2-mediated bacterial cell-to-cell communication.

Guo M, Gamby S, Nakayama S, Smith J, Sintim HO - Sensors (Basel) (2012)

Bottom Line: Analogs of AI-2 have the potential to modulate bacterial behavior.Herein, we demonstrate that when an AI-2 analog, isobutyl DPD (which has been previously shown to be a quorum sensing, QS, quencher in both Escherichia coli and Salmonella typhimurium) is modified with ester groups, which get hydrolyzed once inside the bacterial cells, only QS in E. coli, but not in S. typhimurium, is inhibited.The origin of this differential QS inhibition could be due to differences in analog permeation of the bacterial membranes or ester hydrolysis rates.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA. mguo@umd.edu

ABSTRACT
The universal quorum sensing autoinducer, AI-2, is utilized by several bacteria. Analogs of AI-2 have the potential to modulate bacterial behavior. Selectively quenching the communication of a few bacteria, in the presence of several others in an ecosystem, using analogs of AI-2 is non-trivial due to the ubiquity of AI-2 processing receptors in many bacteria that co-exist. Herein, we demonstrate that when an AI-2 analog, isobutyl DPD (which has been previously shown to be a quorum sensing, QS, quencher in both Escherichia coli and Salmonella typhimurium) is modified with ester groups, which get hydrolyzed once inside the bacterial cells, only QS in E. coli, but not in S. typhimurium, is inhibited. The origin of this differential QS inhibition could be due to differences in analog permeation of the bacterial membranes or ester hydrolysis rates. Such differences could be utilized to selectively target QS in specific bacteria amongst a consortium of other species that also use AI-2 signaling.

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Inhibition of AI-2-mediated β-galactosidase expression in E. coli with various bis-ester analogs of hexyl DPD. [DPD] = 20 μM, [analogs] = 20 μM. Compounds 27–30 represent ester protected hexyl DPD analogs; 27: hexyl DPD bis-methyl ester; 28: hexyl DPD bis-propyl ester; 29: hexyl DPD bis-butyl ester; 30: hexyl DPD bis-pentyl ester.
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f5-sensors-12-03762: Inhibition of AI-2-mediated β-galactosidase expression in E. coli with various bis-ester analogs of hexyl DPD. [DPD] = 20 μM, [analogs] = 20 μM. Compounds 27–30 represent ester protected hexyl DPD analogs; 27: hexyl DPD bis-methyl ester; 28: hexyl DPD bis-propyl ester; 29: hexyl DPD bis-butyl ester; 30: hexyl DPD bis-pentyl ester.

Mentions: Increasing the length of the ester chain to butyl or pentyl either reduced (butyl) or abrogated (pentyl) the inhibitory profile of the DPD analog. In E. coli, the same trend was also observed for the bis-ester derivatives of hexyl DPD (bis-methyl and bis-propyl analogs, but not butyl or pentyl derivatives, were QS inhibitors, Figure 5).


A pro-drug approach for selective modulation of AI-2-mediated bacterial cell-to-cell communication.

Guo M, Gamby S, Nakayama S, Smith J, Sintim HO - Sensors (Basel) (2012)

Inhibition of AI-2-mediated β-galactosidase expression in E. coli with various bis-ester analogs of hexyl DPD. [DPD] = 20 μM, [analogs] = 20 μM. Compounds 27–30 represent ester protected hexyl DPD analogs; 27: hexyl DPD bis-methyl ester; 28: hexyl DPD bis-propyl ester; 29: hexyl DPD bis-butyl ester; 30: hexyl DPD bis-pentyl ester.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376627&req=5

f5-sensors-12-03762: Inhibition of AI-2-mediated β-galactosidase expression in E. coli with various bis-ester analogs of hexyl DPD. [DPD] = 20 μM, [analogs] = 20 μM. Compounds 27–30 represent ester protected hexyl DPD analogs; 27: hexyl DPD bis-methyl ester; 28: hexyl DPD bis-propyl ester; 29: hexyl DPD bis-butyl ester; 30: hexyl DPD bis-pentyl ester.
Mentions: Increasing the length of the ester chain to butyl or pentyl either reduced (butyl) or abrogated (pentyl) the inhibitory profile of the DPD analog. In E. coli, the same trend was also observed for the bis-ester derivatives of hexyl DPD (bis-methyl and bis-propyl analogs, but not butyl or pentyl derivatives, were QS inhibitors, Figure 5).

Bottom Line: Analogs of AI-2 have the potential to modulate bacterial behavior.Herein, we demonstrate that when an AI-2 analog, isobutyl DPD (which has been previously shown to be a quorum sensing, QS, quencher in both Escherichia coli and Salmonella typhimurium) is modified with ester groups, which get hydrolyzed once inside the bacterial cells, only QS in E. coli, but not in S. typhimurium, is inhibited.The origin of this differential QS inhibition could be due to differences in analog permeation of the bacterial membranes or ester hydrolysis rates.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742, USA. mguo@umd.edu

ABSTRACT
The universal quorum sensing autoinducer, AI-2, is utilized by several bacteria. Analogs of AI-2 have the potential to modulate bacterial behavior. Selectively quenching the communication of a few bacteria, in the presence of several others in an ecosystem, using analogs of AI-2 is non-trivial due to the ubiquity of AI-2 processing receptors in many bacteria that co-exist. Herein, we demonstrate that when an AI-2 analog, isobutyl DPD (which has been previously shown to be a quorum sensing, QS, quencher in both Escherichia coli and Salmonella typhimurium) is modified with ester groups, which get hydrolyzed once inside the bacterial cells, only QS in E. coli, but not in S. typhimurium, is inhibited. The origin of this differential QS inhibition could be due to differences in analog permeation of the bacterial membranes or ester hydrolysis rates. Such differences could be utilized to selectively target QS in specific bacteria amongst a consortium of other species that also use AI-2 signaling.

Show MeSH
Related in: MedlinePlus