Antibacterial and Antifungal Activities of New Acylated Derivatives of Epigallocatechin Gallate

Yoshimi Matsumoto,Kunihiko Nishino,Miho Ogawa,Kunihiro Kaihatsu,Akihito Yamaguchi,Nobuo Kato

doi:10.3389/fmicb.2012.00053

Abstract

(−)-Epigallocatechin-3-O-gallate (EGCG) has useful antiviral, antimicrobial, antitoxin, and antitumor properties. Previously, Mori et al. (2008) found that addition of long acyl chains (C16–18) to EGCG enhanced its anti-influenza virus activity up to 44-fold. The chemical stability of EGCG against oxidative degradation was also enhanced by acylation. We further evaluated the in vitro activity spectrum of the EGCG derivatives against a wide range of bacteria and fungi. A series of EGCG O-acyl derivatives were synthesized by lipase-catalyzed transesterification. These derivatives exhibited several-fold higher activities than EGCG, particularly against Gram-positive organisms. Antifungal MICs of the derivatives were also two to fourfold lower than those of EGCG. The activities of the EGCG derivatives against Gram-negative bacteria were not distinguishable from those of EGCG. Among the derivatives evaluated, MICs of dioctanoate and palmitate (C16) for 17 Staphylococcus aureus strains were 4–32 μg/ml, although MIC of EGCG for these 17 strains was ≥128 μg/ml. C16 demonstrated rapid bactericidal activity against methicillin-resistant S. aureus (MRSA) ATCC43300 at ≥16 μg/ml. The enhanced activity of C16 against S. aureus was supported by its increased membrane-permeabilizing activity determined by increased SYTOX Green uptake. The EGCG derivatives were exported in Escherichia coli using the efflux pump AcrAB–TolC. The tolC deletion mutant exhibited higher sensitivity to EGCG and the derivatives than wild-type. Addition of long alkyl chains to EGCG significantly enhanced its activities against several bacteria and fungi, particularly against S. aureus including MRSA. C16 might potentially become under specified circumstances an alternative or supplement to antibiotics and disinfectants in the future.

Highlights

Green tea has long been a daily food in Japan with beneficial health effects
The effect of acyl chain length on antistaphylococcal activity was evaluated (Figure 2) on the basis of the results of a previous study on antiviral activities of the acylated EGCG derivatives against influenza virus. These antiviral activities were increased in an acyl chain length-dependent manner (Mori et al, 2008)
Interaction of catechin with lipid bilayers has been studied in detail (Kumazawa et al, 2004; Uekusa et al, 2007; Kajiya et al, 2008; Kamihira et al, 2008; Sirk et al, 2008, 2009, 2011; Sun et al, 2009)

Summary

Introduction

Green tea has long been a daily food in Japan with beneficial health effects. Antibacterial and antitoxin effects of tea (Camellia sinensis) leaves are already proved in Japan in 1930s (Shimamura, 2009). Recent studies proved that polyphenol components of tea leaves have antitoxin (Hara et al, 1990; Toda et al, 1990; Hisano et al, 2003), antiviral (Mukoyama et al, 1991; Nakayama et al., 1993; Yamaguchi et al, 2002), and antitumor properties (Mukhtar et al, 1992; Shimamura and Hara, 1997) other than antimicrobial activity (Toda et al, 1989; Yam et al, 1997). Tea polyphenols have broad antibacterial spectrum, and inhibit various kinds of pathogenic bacteria such as Bacillus cereus, Campylobacter spp., Clostridium perfringens, Escherichia coli O157, Helicobacter pylori, Legionella pneumophila, Mycobacterium tuberculosis, Mycoplasma www.frontiersin.org pneumonia, Proteus vulgaris, Pseudomonas aeruginosa, Salmonella spp., Serratia marcescens, Staphylococcus spp., oral pathogenic

Methods

Results

Conclusion