The polyphenol (−)-epicatechin gallate disrupts the secretion of virulence-related proteins by Staphylococcus aureus

Abstract

Aim: (−)‐Epicatechin gallate (ECg) modifies the morphology, cell wall architecture and β‐lactam antibiotic susceptibility of Staphylococcus aureus. As these effects result primarily from intercalation into the bacterial cytoplasmic membrane, the capacity of ECg to modulate the secretion of two key staphylococcal virulence factors, coagulase and α‐toxin, was examined. Methods and Results: Bioassays were used to determine coagulase and haemolysin activity in culture supernatants of a number of S. aureus isolates grown in the presence and absence of ECg; α‐toxin secretion was also evaluated by immunoblotting. Growth in ECg reduced the levels of activity of both proteins in culture supernatants; the effects could only be partly explained by ECg‐mediated inhibition of bioactivity and by induction of secreted proteases. Conclusion: ECg suppresses the secretion of coagulase and α‐toxin by clinical isolates of S. aureus. Significance and Impact of the Study: The observation that secretion of key components of staphylococcal virulence can be compromised by a naturally occurring polyphenol supports the notion that ECg and related compounds may have therapeutic utility for the control of infections that are currently difficult to treat due to the propensity of methicillin‐resistant S. aureus to accumulate antibiotic resistance genes.

Recent advances in understanding the antibacterial properties of flavonoids

“…This was demonstrated by examining supernatants from treated S. aureus cultures for the ability to coagulate blood plasma and to lyse erythrocytes. As in the study by Choi et al [20], some direct activity was detected from the flavonoid against ␣-toxin, but not enough to account for the results obtained [128]. The decrease in secretion is unlikely to be related to cell aggregation (and diminished surface area) either, because secretion of the enzyme protease was not inhibited.…”

“…Recent studies have shown that sub-MIC levels of flavonoid inhibit release of this bacterium's virulence factors. Shah et al found that epicatechin gallate prevents the secretion of coagulase and ␣-toxin [128]. This was demonstrated by examining supernatants from treated S. aureus cultures for the ability to coagulate blood plasma and to lyse erythrocytes.…”

Interference of Origanum vulgare L. essential oil on the growth and some physiological characteristics of Staphylococcus aureus strains isolated from foods

“…At 0.015 mL mL À1 the coagulase activity found for the cells were in a range of þ (level 1) to þþ (level 2). It is probable that the much of the reduction in coagulase activity of the cells is due to a prevention of secretion of the proteins as a result of changes in the physical nature of the staphylococcal cytoplasm membrane (Shah, Stapleton, & Taylor, 2008). Moreover, the intercalation of active plant compounds into the cytoplasm membrane may interfere with membrane-associated signal transduction process (Ikigai, Toda, Okubo, Hara, & Shimamura, 1990;Okubo, Ikigai, Toda, & Shimamura, 1989).…”

Impact of the β-Lactam Resistance Modifier (−)-Epicatechin Gallate on the Non-Random Distribution of Phospholipids across the Cytoplasmic Membrane of Staphylococcus aureus

“…Together with a large reduction in the degree of a d -alanyl esterification of cell wall teichoic acid [34], exposure to ECg results in major changes to the overall electrochemical charge profile of the staphylococcal surface (Figure 2). Thus, insertion of ECg into the lipid palisade of the EMRSA-16 CM results in a suboptimal environment in which membrane proteins are forced to operate and this is likely to account for the observed disruption of protein secretion [42] and loss of capacity to form biofilms [35]. …”