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Unravelling the Structural and Molecular Basis Responsible for the Anti-Biofilm Activity of Zosteric Acid.

Cattò C, Dell'Orto S, Villa F, Villa S, Gelain A, Vitali A, Marzano V, Baroni S, Forlani F, Cappitelli F - PLoS ONE (2015)

Bottom Line: Despite its potential, the lack of information concerning the structural and molecular mechanism of action involved in its anti-biofilm activity has limited efforts to generate more potent anti-biofilm strategies.Considerations concerning the relationship between structure and anti-biofilm activity revealed that i) the para-sulfoxy ester group is not needed to exploit the anti-biofilm activity of the molecule, it is the cinnamic acid scaffold that is responsible for anti-biofilm performance; ii) the anti-biofilm activity of ZA derivatives depends on the presence of a carboxylate anion and, consequently, on its hydrogen-donating ability; iii) the conjugated aromatic system is instrumental to the anti-biofilm activities of ZA and its analogues.Using a protein pull-down approach, combined with mass spectrometry, the herein-defined active structure of ZA was matrix-immobilized, and was proved to interact with the E. coli NADH:quinone reductase, WrbA, suggesting a possible role of this protein in the biofilm formation process.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Environmental and Nutritional Sciences, Università degli Studi di Milano, Milano, Italy.

ABSTRACT
The natural compound zosteric acid, or p-(sulfoxy)cinnamic acid (ZA), is proposed as an alternative biocide-free agent suitable for preventive or integrative anti-biofilm approaches. Despite its potential, the lack of information concerning the structural and molecular mechanism of action involved in its anti-biofilm activity has limited efforts to generate more potent anti-biofilm strategies. In this study a 43-member library of small molecules based on ZA scaffold diversity was designed and screened against Escherichia coli to understand the structural requirements necessary for biofilm inhibition at sub-lethal concentrations. Considerations concerning the relationship between structure and anti-biofilm activity revealed that i) the para-sulfoxy ester group is not needed to exploit the anti-biofilm activity of the molecule, it is the cinnamic acid scaffold that is responsible for anti-biofilm performance; ii) the anti-biofilm activity of ZA derivatives depends on the presence of a carboxylate anion and, consequently, on its hydrogen-donating ability; iii) the conjugated aromatic system is instrumental to the anti-biofilm activities of ZA and its analogues. Using a protein pull-down approach, combined with mass spectrometry, the herein-defined active structure of ZA was matrix-immobilized, and was proved to interact with the E. coli NADH:quinone reductase, WrbA, suggesting a possible role of this protein in the biofilm formation process.

No MeSH data available.


Related in: MedlinePlus

Biological activity of ZA-related compounds.Biological activity of each ZA-related compound at the different tested concentrations. For an understanding of the meaning of each trend refer to the ‘Results and discussion’ section. Yellow: no biological activity; Green: anti-biofilm activity; Blu: promotion of biofilm formation; Red: biocidal effect.
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pone.0131519.g006: Biological activity of ZA-related compounds.Biological activity of each ZA-related compound at the different tested concentrations. For an understanding of the meaning of each trend refer to the ‘Results and discussion’ section. Yellow: no biological activity; Green: anti-biofilm activity; Blu: promotion of biofilm formation; Red: biocidal effect.

Mentions: With the aim of identifying trends, planktonic growth and cell adhesion data were grouped to obtain a global picture of the biological activity of each ZA-related compound at the different concentrations (Fig 6). The compounds showed: i) no biological activity (no reduction of the number of adhered cells and no planktonic growth effect), ii) anti-biofilm activity (reduction of the number of adhered cells and no planktonic growth effect), iii) increased biofilm formation (increase in the number of adhered cells and no planktonic growth effect), and iv) biocidal effect (in contrast to the above trends, planktonic growth was inhibited while the number of adhered cells either increased or decreased). Five molecules (7, 12, 18, 19, 39) induced no biological activity at low and middle concentrations, or biocidal effect at the maximum concentration (Trend 1). Nine molecules (24, 25, 27, 29–31, 40, 42, 43) promoted biofilm formation at the lowest concentration but showed no biological activity or biocidal effect at middle and high concentrations (Trend 2). Nineteen molecules (1–6, 8–11, 13–15, 20, 21, 23, 26, 28, 41) had no biological activity at low concentration, showed an anti-biofilm activity at middle concentrations and induced biocidal effect at the maximum concentration (Trend 3). Eight molecules (ZA, 16, 17, 22, 33–36) promoted biofilm formation at the lowest concentration, showed an anti-biofilm activity at middle concentrations, and induced a biocidal effect at the maximum concentration (Trend 4). Finally, molecules 32, 37 and 38 showed a peculiar trend (Trend 5): molecule 32 showed anti-biofilm activity at the lowest concentration, no biological activity at middle concentrations and biocidal effect at the highest concentration, molecule 37 promoted biofilm formation at concentrations 0.183, 1.83 and 183 μM, inhibited biofilm formation at 18.3 μM and induced a biocidal effect at the highest concentration; molecule 38 promoted biofilm formation at all tested concentrations except for the 183 μM, where there was no biological activity.


Unravelling the Structural and Molecular Basis Responsible for the Anti-Biofilm Activity of Zosteric Acid.

Cattò C, Dell'Orto S, Villa F, Villa S, Gelain A, Vitali A, Marzano V, Baroni S, Forlani F, Cappitelli F - PLoS ONE (2015)

Biological activity of ZA-related compounds.Biological activity of each ZA-related compound at the different tested concentrations. For an understanding of the meaning of each trend refer to the ‘Results and discussion’ section. Yellow: no biological activity; Green: anti-biofilm activity; Blu: promotion of biofilm formation; Red: biocidal effect.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4488431&req=5

pone.0131519.g006: Biological activity of ZA-related compounds.Biological activity of each ZA-related compound at the different tested concentrations. For an understanding of the meaning of each trend refer to the ‘Results and discussion’ section. Yellow: no biological activity; Green: anti-biofilm activity; Blu: promotion of biofilm formation; Red: biocidal effect.
Mentions: With the aim of identifying trends, planktonic growth and cell adhesion data were grouped to obtain a global picture of the biological activity of each ZA-related compound at the different concentrations (Fig 6). The compounds showed: i) no biological activity (no reduction of the number of adhered cells and no planktonic growth effect), ii) anti-biofilm activity (reduction of the number of adhered cells and no planktonic growth effect), iii) increased biofilm formation (increase in the number of adhered cells and no planktonic growth effect), and iv) biocidal effect (in contrast to the above trends, planktonic growth was inhibited while the number of adhered cells either increased or decreased). Five molecules (7, 12, 18, 19, 39) induced no biological activity at low and middle concentrations, or biocidal effect at the maximum concentration (Trend 1). Nine molecules (24, 25, 27, 29–31, 40, 42, 43) promoted biofilm formation at the lowest concentration but showed no biological activity or biocidal effect at middle and high concentrations (Trend 2). Nineteen molecules (1–6, 8–11, 13–15, 20, 21, 23, 26, 28, 41) had no biological activity at low concentration, showed an anti-biofilm activity at middle concentrations and induced biocidal effect at the maximum concentration (Trend 3). Eight molecules (ZA, 16, 17, 22, 33–36) promoted biofilm formation at the lowest concentration, showed an anti-biofilm activity at middle concentrations, and induced a biocidal effect at the maximum concentration (Trend 4). Finally, molecules 32, 37 and 38 showed a peculiar trend (Trend 5): molecule 32 showed anti-biofilm activity at the lowest concentration, no biological activity at middle concentrations and biocidal effect at the highest concentration, molecule 37 promoted biofilm formation at concentrations 0.183, 1.83 and 183 μM, inhibited biofilm formation at 18.3 μM and induced a biocidal effect at the highest concentration; molecule 38 promoted biofilm formation at all tested concentrations except for the 183 μM, where there was no biological activity.

Bottom Line: Despite its potential, the lack of information concerning the structural and molecular mechanism of action involved in its anti-biofilm activity has limited efforts to generate more potent anti-biofilm strategies.Considerations concerning the relationship between structure and anti-biofilm activity revealed that i) the para-sulfoxy ester group is not needed to exploit the anti-biofilm activity of the molecule, it is the cinnamic acid scaffold that is responsible for anti-biofilm performance; ii) the anti-biofilm activity of ZA derivatives depends on the presence of a carboxylate anion and, consequently, on its hydrogen-donating ability; iii) the conjugated aromatic system is instrumental to the anti-biofilm activities of ZA and its analogues.Using a protein pull-down approach, combined with mass spectrometry, the herein-defined active structure of ZA was matrix-immobilized, and was proved to interact with the E. coli NADH:quinone reductase, WrbA, suggesting a possible role of this protein in the biofilm formation process.

View Article: PubMed Central - PubMed

Affiliation: Department of Food Environmental and Nutritional Sciences, Università degli Studi di Milano, Milano, Italy.

ABSTRACT
The natural compound zosteric acid, or p-(sulfoxy)cinnamic acid (ZA), is proposed as an alternative biocide-free agent suitable for preventive or integrative anti-biofilm approaches. Despite its potential, the lack of information concerning the structural and molecular mechanism of action involved in its anti-biofilm activity has limited efforts to generate more potent anti-biofilm strategies. In this study a 43-member library of small molecules based on ZA scaffold diversity was designed and screened against Escherichia coli to understand the structural requirements necessary for biofilm inhibition at sub-lethal concentrations. Considerations concerning the relationship between structure and anti-biofilm activity revealed that i) the para-sulfoxy ester group is not needed to exploit the anti-biofilm activity of the molecule, it is the cinnamic acid scaffold that is responsible for anti-biofilm performance; ii) the anti-biofilm activity of ZA derivatives depends on the presence of a carboxylate anion and, consequently, on its hydrogen-donating ability; iii) the conjugated aromatic system is instrumental to the anti-biofilm activities of ZA and its analogues. Using a protein pull-down approach, combined with mass spectrometry, the herein-defined active structure of ZA was matrix-immobilized, and was proved to interact with the E. coli NADH:quinone reductase, WrbA, suggesting a possible role of this protein in the biofilm formation process.

No MeSH data available.


Related in: MedlinePlus