PLoS ONE (2015-01-01)

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

  • Cristina Cattò,
  • Silvia Dell'Orto,
  • Federica Villa,
  • Stefania Villa,
  • Arianna Gelain,
  • Alberto Vitali,
  • Valeria Marzano,
  • Sara Baroni,
  • Fabio Forlani,
  • Francesca Cappitelli

DOI
https://doi.org/10.1371/journal.pone.0131519
Journal volume & issue
Vol. 10, no. 7
p. e0131519

Abstract

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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.