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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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Black bars: AI-2 or analogs-mediated expression of β-galactosidase in S. typhimurium (MET715: LuxS−). Pink bars: AI-2 or analogs-mediated expression of β-galactosidase in E. coli LW7/LuxS−. AI-2 or bis-ester analogs of AI-2 (20 μM) were added to the bacterial strains, which do not produce their own AI-2. Compounds 19–22 represent ester-protected DPD analogs: 19: DPD bis-methyl ester; 20: DPD bis-propyl ester; 21: DPD bis-butyl ester; 22: DPD bis-pentyl ester.
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f3-sensors-12-03762: Black bars: AI-2 or analogs-mediated expression of β-galactosidase in S. typhimurium (MET715: LuxS−). Pink bars: AI-2 or analogs-mediated expression of β-galactosidase in E. coli LW7/LuxS−. AI-2 or bis-ester analogs of AI-2 (20 μM) were added to the bacterial strains, which do not produce their own AI-2. Compounds 19–22 represent ester-protected DPD analogs: 19: DPD bis-methyl ester; 20: DPD bis-propyl ester; 21: DPD bis-butyl ester; 22: DPD bis-pentyl ester.

Mentions: Bis-ester-protected AI-2 analogs (with different ester chains; methyl, propyl, butyl and pentyl) were all effective lsr expression inducers in E. coli (see Figure 3). For S. typhimurium, it appears that LsrR is not as good a repressor (compared to E. coli) and significant expression of the lacZ gene was observed even in the absence of added DPD (see control, Figure 3). Nonetheless, it is apparent that more LacZ protein was present in S. typhimurium in the presence of AI-2 than when AI-2 was not present [about 30% more LacZ present when AI-2 is added; see Figure 3, compare the histograms for “LuxS- + AI-2” and LuxS- (no AI-2 added)].


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)

Black bars: AI-2 or analogs-mediated expression of β-galactosidase in S. typhimurium (MET715: LuxS−). Pink bars: AI-2 or analogs-mediated expression of β-galactosidase in E. coli LW7/LuxS−. AI-2 or bis-ester analogs of AI-2 (20 μM) were added to the bacterial strains, which do not produce their own AI-2. Compounds 19–22 represent ester-protected DPD analogs: 19: DPD bis-methyl ester; 20: DPD bis-propyl ester; 21: DPD bis-butyl ester; 22: DPD bis-pentyl ester.
© Copyright Policy
Related In: Results  -  Collection

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

f3-sensors-12-03762: Black bars: AI-2 or analogs-mediated expression of β-galactosidase in S. typhimurium (MET715: LuxS−). Pink bars: AI-2 or analogs-mediated expression of β-galactosidase in E. coli LW7/LuxS−. AI-2 or bis-ester analogs of AI-2 (20 μM) were added to the bacterial strains, which do not produce their own AI-2. Compounds 19–22 represent ester-protected DPD analogs: 19: DPD bis-methyl ester; 20: DPD bis-propyl ester; 21: DPD bis-butyl ester; 22: DPD bis-pentyl ester.
Mentions: Bis-ester-protected AI-2 analogs (with different ester chains; methyl, propyl, butyl and pentyl) were all effective lsr expression inducers in E. coli (see Figure 3). For S. typhimurium, it appears that LsrR is not as good a repressor (compared to E. coli) and significant expression of the lacZ gene was observed even in the absence of added DPD (see control, Figure 3). Nonetheless, it is apparent that more LacZ protein was present in S. typhimurium in the presence of AI-2 than when AI-2 was not present [about 30% more LacZ present when AI-2 is added; see Figure 3, compare the histograms for “LuxS- + AI-2” and LuxS- (no AI-2 added)].

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