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 S. 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 Youngken 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, costunolide and dehydrocostus lactone. Laurenobiolide was the most abundant in the twig bark of the tulip tree, supporting the twig bark's historical and cultural usage in poultices and teas.

Figure 1

Primary active compound against MSSA was determined to be the sesquiterpene lactone laurenobiolide in this study. Other sesquiterpene lactones identified from Liriodendron tulipifera and magnolias were tulipinolide, epi-tulipinolide, costunolide, and dehydrocostus lactone.

Figure 2

MSSA inhibition assay with L. tulipifera plant parts. Twig, trunk bark, flower, and leaf were directly placed onto MSSA plates. Plant parts were surface sterilized with methanol and dried prior to evaluation. The zone of inhibition can be seen for the twig specimen. Gentamicin sulfate was used as the positive control.

Figure 3

Sesquiterpene lactones in Liriodendron tulipifera and three other Magnolia spp. (A) Epi-tulipinolide (E), laurenobiolide (L), and tulipinolide (T) were only detected in L. tulipifera extracts. (B) Extracted ion chromatogram (m/z 231) shows the base peak of the three acetylated sesquiterpene lactones in L. tulipifera, and an unidentified metabolite in M. virginiana and M. acuminata. (C) Extracted ion chromatogram (m/z 233) shows the presence of costunolide in L. tulipifera, M. virginiana and M. acuminata. (D) Among the magnolias tested, only the M. macrophylla extract showed anti-MSSA activity. Gentamicin sulfate, an aminoglycoside antibiotic, was used as the positive control (20 μg/disk; upper left quadrant on each plate). The test concentration of the extracts was 200 μg/disk, and each extract was tested in duplicate. Negative controls are in the bottom left quadrant of each plate.