Biochemometric analysis reveals complimentary bacterial inhibitory functionalities of the medicinal lichen Usnea barbata
14 December 2016 (online)
Resistance to traditional antibacterials is a global problem, and new strategies are needed against bacterial pathogens. Bacteria produce an arsenal of virulence factors, which are controlled by a density-dependent regulatory system known as 'quorum sensing.' Targeting the pathways that produce these virulence factors is a promising new strategy for anti-infective therapeutics. With this research project, we sought to identify antimicrobial and anti-virulence compounds from the lichen Usnea barbata. U. barbata has been widely employed by native peoples across North America, and has documented medical use in Europe as early as the 18th century [1,2]. To identify active compounds from this lichen, biochemometric approaches were applied, which integrate chemical and biological activity datasets to identify putative bioactive components from complex mixtures . U. barbata evidenced activity in multiple mechanistic pathways of inhibiting growth and signalling in methicillin-resistant Staphylococcus aureus (MRSA). Biochemometric analysis of U. barbata crude extract and flash chromatography fractions revealed known antimicrobial compounds, including usnic acid, as well as potentially new bioactive metabolites which inhibited MRSA growth at low µg/mL levels. In addition, three subfractions were potent inhibitors of the MRSA quorum sensing system, but not antibacterial. Analysis identified several unknown bioactive metabolites that are currently undergoing structure elucidation. The application of biochemometric methods could be a particularly effective tool for integrating biological and chemical data sets, and efficiently guide isolation and discovery efforts for novel bioactive natural products. To date, only a few natural products have been identified as quorum sensing inhibitors, and the identification of new leads with this activity could be extremely important to the future development of anti-infective therapeutics.
Acknowledgements: Dr. Daniel Todd is acknowledged for technical assistance.
Keywords: Biochemometrics, quorum sensing, antibacterial, lichen, ethnopharmacology, Usnea barbata, anti-virulence,.
 Crawford, SD. Lichens Used in Traditional Medicine. In: Rankovic', B, editor. Lichen Secondary Metabolites. Switzerland: Springer International; 2015: 27 – 80
 Lebail, J.B.E.F., Des lichens, considérés sous le point de vue économique, médical, et physiologique (nutrition). M.D. thesis, Faculté de Médecine de Paris, France, 1853
 Kellogg, JJ, Todd, DA, Egan, JM, Raja, HA, Oberlies, NH, Kvalheim, OM, Cech, NB. Biochemometrics for natural products research: comparison of data analysis approaches and application to identification of bioactive compounds. J Nat Prod 2016; 79: 376 – 386
No conflict of interest has been declared by the author(s).