Activity of the tea component epicatechin gallate and analogues against methicillin-resistant Staphylococcus aureus

J. M. T. Hamilton-Miller* and S. Shah

Department of Medical Microbiology, Royal Free and University College Medical School, Royal Free Campus, London NW3 2PF, UK

Sir,

We have reported1 that a crude extract of tea (Camellia sinensis), besides exerting a direct antibacterial effect on methicillin-resistant Staphylococcus aureus (MRSA) (MIC 280 mg/L, or approximately one-tenth ‘cup-of-tea’ concentration), reversed methicillin resistance in such organisms. The latter activity (which we call ‘activity II’) could be separated from the former (‘activity I’), and was more potent, manifesting at concentrations as low as a 100-fold dilution of a ‘cup-of-tea’. We also reported the isolation of the active constituent, which we called ‘compound P’. At the time of publication, we were constrained by Intellectual Property considerations from disclosing the chemical nature of compound P.

Since we published, Shiota et al.2 have shown that the tea component epicatechin gallate (ECG) acts synergically with oxacillin against four MRSA strains. In view of this, we wish to state here that our compound P was ECG (Patent Application PCT GB/95/02107, filed 6 September 1995) and also to report on the ability of compounds of related chemical structure to show activities I and II.

The 15 compounds shown in the TableGo (obtained from Unilever Ltd, Colworth, UK) were assayed for activity I and activity II as described previously,1 with S. aureus Oxford and MRSA US12, respectively, as indicator strains.


View this table:
[in this window]
[in a new window]
 
Table. Assay of compounds structurally analogous to epicatechin gallate for inhibitory activity (‘activity I’) and synergic activity with methicillin (‘activity II’)
 
Ten compounds showed activity I, as briefly reported previously,3 with MNICs between 200 and 25 mg/L. Five compounds also showed activity II (MNICs 58–4 mg/L), which was always the more potent. ECG had the greatest activity II (MNIC 1.6 mg/L), but had very little activity I (MIC 512 mg/L in brain heart infusion broth).4

Correlating these results with the known chemical composition of the brews made from green and black tea5 shows that the direct antistaphylococcal effect of the former (activity I) is accounted for by epigallocatechin gallate and epigallocatechin, and of the latter mainly by its content of theaflavins. The methicillin-resistance-reversing action (activity II) of either brew is due chiefly to ECG.

ECG appears to act by inhibiting the synthesis of PBP2', as has also been reported recently for diterpenes such as totarol.6 The mechanisms of action of two other compounds7,8 that act synergically with methicillin, tellimagrandin I and Cibacron Blue F3GA, are not known.

Notes

J Antimicrob Chemother 2000; 46: 852–853

* Corresponding author. Tel: + 44-20-7794-0500; Fax: + 44-20-7435-9694; E-mail: j.hamilton-miller{at}rfhsm.ac.uk Back

References

1 . Yam, T. S., Hamilton-Miller, J. M. T. & Shah, S. (1998). The effect of a component of tea (Camellia sinensis) on methicillin resistance, PBP2' synthesis and ß-lactamase production in Staphylococcus aureus. Journal of Antimicrobial Chemotherapy 42, 211–16.[Abstract]

2 . Shiota, S., Shimizu, M., Mizushima, T., Ito, H., Hatano, T., Yoshida, T. et al. (1999). Marked reduction in the minimum inhibitory concentration (MIC) of ß-lactams in methicillin-resistant Staphylococcus aureus produced by epicatechin gallate, an ingredient of green tea (Camellia sinensis). Biological and Pharmaceutical Bulletin 22, 1388–90.[Medline]

3 . Yam, T. S., Shah, S. & Hamilton-Miller, J. M. T. (1997). Microbiological activity of whole and fractionated crude extracts of tea (Camellia sinensis), and of tea components. FEMS Microbiology Letters 152, 169–74.[ISI][Medline]

4 . Hamilton-Miller, J. M. T. & Shah, S. (1999). Disorganization of cell division of methicillin-resistant Staphylococcus aureus by a component of tea (Camellia sinensis): a study by electron microscopy. FEMS Microbiology Letters 176, 463–9.[ISI][Medline]

5 . Anonymous (1991). Tea. IARC Monographs 51, 207–71.[Medline]

6 . Nicolson, K., Evans, G. & O'Toole, P. W. (1999). Potentiation of methicillin activity against methicillin-resistant Staphylococcus aureus by diterpenes. FEMS Microbiology Letters 179, 233–9.[ISI][Medline]

7 . Shoita, S., Shimizu, M., Mizusima, T., Ito, H., Hatano, T., Yoshida, T. et al. (2000). Restoration of effectiveness of ß-lactams on methicillin-resistant Staphylococcus aureus by tellimagrandin I from rose red. FEMS Microbiology Letters 185, 135–8.[ISI][Medline]

8 . Shirai, C., Sugai, M., Komatsuzawa, H., Ohta, K., Yamakido, M. & Suginaka, H. (1998). A triazine dye, Cibacron Blue F3GA, decreases oxacillin resistance levels in methicillin-resistant Staphylococcus aureus. Antimicrobial Agents and Chemotherapy 42, 1278–80.[Abstract/Free Full Text]