Screening the PRISM library against Staphylococcus aureus reveals a sesquiterpene lactone from Liriodendron tulipifera with inhibitory activity

Abstract

Infections caused by the bacterium Staphylococcus aureus continue to pose threats to human health and put a financial burden on the healthcare system. The overuse of antibiotics has contributed to mutations leading to the emergence of methicillin-resistant Staphylococcus aureus, and there is a critical need for the discovery and development of new antibiotics to evade drug resistant bacteria. Medicinal plants have shown promise as sources of new small molecule therapeutics with potential uses against pathogenic infections. The Principal Rhode Island Secondary Metabolite (PRISM) library is a botanical extract library generated from specimens in the URI Heber W. Youngken Jr. Medicinal Garden by upper-division undergraduate students. PRISM extracts were screened for activity against strains of methicillin-susceptible S. aureus (MSSA). An extract generated from the tulip tree (Liriodendron tulipifera) demonstrated growth inhibition against MSSA, and a bioassay-guided approach identified a sesquiterpene lactone, laurenobiolide, as the active constituent. Intriguingly, its isomers tulipinolide and epi-tulipinolide lacked potent activity against MSSA. Laurenobiolide also proved to be more potent against MSSA than the structurally similar sesquiterpene lactones constunolide and dehydrocostus lactone. Laurenobioloide was most abundant in the twig bark of the tulip tree, supporting the historical and cultural usage of twig bark in poultices and teas. ABSTRACT GRAPHIC O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=94 SRC="FIGDIR/small/494747v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@952221org.highwire.dtl.DTLVardef@f3a5daorg.highwire.dtl.DTLVardef@d91daorg.highwire.dtl.DTLVardef@e2a845_HPS_FORMAT_FIGEXP M_FIG C_FIG