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Catechin-mediated restructuring of a bacterial toxin inhibits activity

Author:
Chang, En Hyung, Huang, Joanne, Lin, Zixiang, Brown, Angela C.
Source:
Biochimica et biophysica acta 2019 v.1863 no.1 pp. 191-198
ISSN:
0304-4165
Subject:
Actinobacillus actinomycetemcomitans, antibacterial properties, bacteria, bacterial toxins, catechin, cholesterol, circular dichroism spectroscopy, confocal microscopy, cytotoxicity, fluorescence, humans, leaves, leukocytes, leukotoxins, mechanism of action, polyphenols, staining, tea, virulence
Abstract:
Catechins, polyphenols derived from tea leaves, have been shown to have antibacterial properties, through direct killing of bacteria as well as through inhibition of bacterial toxin activity. In particular, certain catechins have been shown to have bactericidal effects on the oral bacterium, Aggregatibacter actinomycetemcomitans, as well as the ability to inhibit a key virulence factor of this organism, leukotoxin (LtxA). The mechanism of catechin-mediated inhibition of LtxA has not been shown.In this work, we studied the ability of six catechins to inhibit LtxA-mediated cytotoxicity in human white blood cells, using Trypan blue staining, and investigated the mechanism of action using a combination of techniques, including fluorescence and circular dichroism spectroscopy, confocal microscopy, and surface plasmon resonance.We found that all the catechins except (−)-catechin inhibited the activity of this protein, with the galloylated catechins having the strongest effect. Pre-incubation of the toxin with the catechins increased the inhibitory action, indicating that the catechins act on the protein, rather than the cell. The secondary structure of LtxA was dramatically altered in the presence of catechin, which resulted in an inhibition of toxin binding to cholesterol, an important initial step in the cytotoxic mechanism of the toxin.These results demonstrate that the catechins inhibit LtxA activity by altering its structure to prevent interaction with specific molecules present on the host cell surface.Galloylated catechins modify protein toxin structure, inhibiting the toxin from binding to the requisite molecules on the host cell surface.
Agid:
6179522