Identification of Ellagic Acid Rhamnoside as a Bioactive Component of a Complex Botanical Extract with Anti-biofilm Activity

Abstract

<i>Staphylococcus aureus</i> is a leading cause of hospital-acquired infections. It is listed among the top "serious threats" to human health in the USA, due in large part to rising rates of resistance. Many <i>S. aureus</i> infections are recalcitrant to antibiotic therapy due to their ability to form a biofilm, which acts not only as a physical barrier to antibiotics and the immune system, but results in differences in metabolism that further restricts antibiotic efficacy. Development of a modular strategy to synthesize a library of phenolic glycosides allowed for bioactivity testing and identification of anti-biofilm compounds within an extract of the elmleaf blackberry (<i>Rubus ulmifolius</i>). Two ellagic acid (EA) derivatives, EA xyloside and EA rhamnoside, have been identified as components of the <i>Rubus</i> extract. In addition, EA rhamnoside has been identified as an inhibitor of biofilm formation, with activity comparable to the complex extract 220D-F2 (composed of a mixture of EA glycosides), and confirmed by confocal laser scanning microscopy analyses.