ORIGINAL ARTICLE Detailed studies on Quercus infectoria Olivier (nutgalls) as an alternative treatment for methicillin-resistant Staphylococcus aureus infections S. Chusri 1 and S.P. Voravuthikunchai 1,2 1 Department of Microbiology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, Thailand 2 Natural Products Research Center, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, Thailand Introduction The continuing emergence and development of resistance to existing antibacterial agents by bacteria has created the need for new antibacterial compounds that exhibit acti- vity against these resistant strains (Levy and Marshall 2004; Norrby et al. 2005). Methicillin-resistant Staphylo- coccus aureus (MRSA) has become increasingly wide- spread as a major cause of both nosocomial and community infections. This situation has placed limits on our options to treat infections by this organism. Glyco- peptide derivatives, such as vancomycin and teicoplanin, are now considered to be agents of last resort for the treatment of MRSA infections (Ferrara 2007). In 2002, vancomycin-resistant Staph. aureus (VRSA) strains emerged in the United States (Centers for Disease Control and Prevention 2002; Chang et al. 2003), followed by reports of these isolates from other parts of the world (Biedenbach et al. 2007; Emaneini et al. 2007). Therefore, before therapy with vancomycin and teicoplanin fails completely, we need to find some alternative antibacterial agents against MRSA infections. Natural products and their derivatives have continued to be the most significant sources of new leads into the development of new pharmaceutical agents. Approxi- mately 25% of modern medications have been derived from previously used plant remedies (Liu and Wang 2008). More than 50% of both anti-infectious and Keywords amoxicillin, methicillin-resistant Staphylococcus aureus, oxacillin, penicillin, pseudomulticellular bacteria, Quercus infectoria. Correspondence Supayang P. Voravuthikunchai, Department of Microbiology and Natural Products Research Center, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand. E-mail: supayang.v@psu.ac.th 2008 ⁄ 0613: received 10 April 2008, revised 4 July 2008 and accepted 05 July 2008 doi:10.1111/j.1365-2672.2008.03979.x Abstract Aims: To investigate the antimethicillin-resistant Staphylococcus aureus (MRSA) mechanism of Quercus infectoria (nutgalls) extract and its components. Methods and Results: Ethanol extract, an ethyl acetate fraction I, gallic acid and tannic acid could inhibit the growth of clinically isolated MRSA strains with minimum inhibitory concentration values between 63 and 250 lg ml )1 . Clumps of partly divided cocci with thickened cell wall were observed by trans- mission electron microscopy in the cultures of MRSA incubated in the presence of the ethanol extract, the ethyl acetate fraction I and tannic acid. Because cell wall structure of the organism structures seemed to be a possible site for anti- bacterial mechanisms, their effect with representative b-lactam antibiotics were determined. Synergistic effects with fractional inhibitory concentration index ranged from 0Æ24 to 0Æ37 were observed with 76% and 53% of the tested strains for the combination of the ethanol extract with amoxicillin and penicillin G, respectively. Conclusions: The appearance of pseudomulticellular bacteria in the treated cells and the synergistic effect of the plant extract with b-lactamase-susceptible penicillins suggest that the extract may interfere with staphylococcal enzymes including autolysins and b-lactamase. Significance and Impact of the Study: Our results provide scientific data on the use of the nutgalls, which contain mainly tannin contents up to 70% for the treatment of staphylococcal infections. Journal of Applied Microbiology ISSN 1364-5072 ª 2008 The Authors Journal compilation ª 2008 The Society for Applied Microbiology, Journal of Applied Microbiology 106 (2009) 89–96 89