Activity of Scottish Plant, Lichen and Fungal Endophyte Extracts against Mycobacterium aurum and Mycobacterium tuberculosis Andréa Y. Gordien 1 , Alexander I. Gray 1 , Kevin Ingleby 2 , Scott G. Franzblau 3 and Véronique Seidel 1 * 1 Natural Products Research Laboratories, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK 2 Centre for Ecology and Hydrology, Edinburgh, Bush Estate, Penicuik, UK 3 Institute for Tuberculosis Research, College of Pharmacy, University of Illinois, Chicago, USA With tuberculosis the leading bacterial killer worldwide and other mycobacterial diseases on the increase, the search for new antimycobacterial agents is timely. In this study, extracts from plants, lichens and fungal endo- phytes of Scottish provenance were screened for activity against Mycobacterium aurum and M. tuberculosis H 37 Rv. The best activity against M. aurum was observed for extracts of Juniperus communis roots and Cladonia arbuscula (MIC = 4 μg/mL), and a fungal endophyte isolated from Vaccinium myrtillus (MIC = 8 μg/mL). The best activity against M. tuberculosis was observed for extracts of C. arbuscula, Empetrum nigrum, J. communis roots, Calluna vulgaris aerial parts, Myrica gale roots and stems (93 to 99% inhibition at 100 μg/mL). Potent antitubercular activity (90 to 96% inhibition at 100 μg/mL) was also observed for the ethanol extracts of Xero- comus badius, Chalciporus piperatus, Suillus luteus and of endophytes isolated from C. vulgaris, E. nigrum, Vaccinium vitis-idaea and V. myrtillus. The results obtained this study provide, in part, some scientific basis for the traditional use of some of the selected plants in the treatment of tuberculosis. They also indicate that fungal endophytes recovered from Scottish plants are a source of antimycobacterial agents worthy of further investigation. Copyright © 2009 John Wiley & Sons, Ltd. Keywords: antimycobacterial activity; endophytes; Scottish plants; lichens; Mycobacterium aurum; Mycobacterium tuberculosis. INTRODUCTION Tuberculosis (TB) is currently the leading bacterial killer worldwide and has been declared a global health emergency. The resurgence of TB over the past two decades, due in part to the spread of HIV/AIDS, is now posing a serious threat to healthcare systems, especially with the increase in multidrug resistant (MDR-TB) cases (WHO, 2008). Current antitubercular treatments involve a long course of a combination of antibiotics with toxic side effects leading to poor patient compli- ance, which contributes to sustaining MDR-TB. There- fore, it has become timely to discover new antitubercular drugs (O’Brien and Nunn, 2001). Additionally, new antimycobacterial agents are needed to improve the treatment of opportunistic diseases caused by non- tuberculous mycobacteria (NTM) which are also on the increase (Gillespie et al., 2001). Mycobacteria thrive in soils which are wet, acidic and covered with dense vegetation primarily composed of mosses, ericaceous plants and conifers (Kazda, 2000). Such an environment is typical of the heaths and bog- lands of Scotland where many ericaceous and conifer plants grow well, often in symbiosis with beneficial micro-organisms (i.e., endophytes) (Piercey et al., 2002; Urcelay, 2002; Verkley et al., 2003; Pirttila et al., 2003; 2005). Given the tendency of such plants to develop in this unique ecosystem despite the mycobacterial chal- lenge in the soil, we anticipated that they, and/or their associated endophytes, were likely to exhibit some anti- mycobacterial activity. Thus, this study was initiated, as part of our ongoing work on antimicrobial products from natural sources (Habeeb et al., 2007; Liu, et al., 2007; Rahman et al., 2008), to explore the activity of a selection of Scottish plants and endophytes against tuberculous and non-tuberculous mycobacteria (Tables 1–5). Several plants, as well as a lichen species, used as traditional remedies for the treatment of tuberculosis and other respiratory diseases were also included in the screening program. MATERIALS AND METHODS Plant and lichen material. The botanical names and voucher code numbers of the plant and lichen species investigated are presented in Table 1. Pulmonaria offi- cinalis was collected in Maryhill, Glasgow, Scotland, in April 2004. Skimmia japonica was collected in Bishopbriggs; Polygonum persicaria and Rumex obtusi- folius were colleted in Helensburgh, Scotland, in July 2005. C. vulgaris, E. nigrum and C. arbuscula were col- lected in Whim Moss; Anemone nemorosa and Lonicera * Correspondence to: Dr V. Seidel, Natural Products Research Labora- tories, Strathclyde Institute of Pharmacy and Biomedical Sciences, Uni- versity of Strathclyde, Glasgow, UK. E-mail: veronique.seidel@strath. ac.uk Contract/grant sponsor: EPSRC; contract/grant number: EP/D504988/1. Received 12 June 2009 Revised 09 July 2009 Copyright © 2009 John Wiley & Sons, Ltd. Accepted 14 July 2009 PHYTOTHERAPY RESEARCH Phytother. Res. 24: 692–698 (2010) Published online 13 October 2009 in Wiley InterScience (www.interscience.wiley.com) DOI: 10.1002/ptr.2988