Antibacterial-guided fractionation of the Dictyoceratid sponges Lamellodysidea sp. and two samples of Dysidea granulosa yielded 14 polybrominated, diphenyl ethers including one new methoxy-containing compound (8). Their structures were elucidated by interpretation of spectroscopic data of the natural product and their methoxy derivatives. Most of the compounds showed strong antimicrobial activity with low- to sub-microgram mL−1 minimum inhibitory concentrations against drug-susceptible and drug-resistant strains of Staphylococcus aureus and Enterococcus faecium, and two compounds inhibited Escherichia coli in a structure-dependent manner.

Chemical screening libraries often feature natural product extracts (NPEs) due to the intriguing biological activities they possess and the structural diversity found in their individual components. A research project originally designed to create an extract library of every specimen in the University of Rhode Island (URI) Heber W. Youngken Jr. Medicinal Garden soon turned into a laboratory-based teaching project in which upper-division undergraduate students generated and analyzed extracts in an academic minisemester project. Additionally, motivated upper-division undergraduates carried out independent research isolating biologically active molecules. Hands-on laboratory activities enhanced students’ knowledge of methodologies and workflows associated with extract analysis and biological evaluation of botanical extracts. The synergy of the laboratory course with the independent study contributed to workforce preparation and library generation.

The emergence of multi-drug resistant pathogenic bacteria represents a serious and growing threat to national healthcare systems. Most pressing is an immediate need for the development of novel antibacterial agents to treat Gram-negative multi-drug resistant infections, including the opportunistic, hospital-derived pathogen, Acinetobacter baumannii. Herein we report a naturally occurring 1,2-benzisoxazole with minimum inhibitory concentrations as low as 6.25 μg ml−1 against clinical strains of multi-drug resistant A. baumannii and investigate its possible mechanisms of action. This molecule represents a new chemotype for antibacterial agents against A. baumannii and is easily accessed in two steps via de novo synthesis. In vitro testing of structural analogs suggest that the natural compound may already be optimized for activity against this pathogen. Our results demonstrate that supplementation of 4-hydroxybenzoate in minimal media was able to reverse 1,2-benzisoxazole’s antibacterial effects in A. baumannii. A search of metabolic pathways involving 4-hydroxybenzoate coupled with molecular modeling studies implicates two enzymes, chorismate pyruvate-lyase and 4-hydroxybenzoate octaprenyltransferase, as promising leads for the target of 3,6-dihydroxy-1,2-benzisoxazole.

Growth in the biomedical and biotechnology sectors requires a highly trained and highly skilled workforce to answer the next great scientific questions. Undergraduate laboratory courses incorporating hands-on training based in authentic research position soon-to-be graduates to learn in environments that mirror those of academic, industrial, and government laboratories. Mass spectrometry is one of the most broadly applied analyses carried out in the biomedical and pharmaceutical sciences, and thus, it is essential that upper-division students gain hands-on experience in techniques and analytical workflows in mass spectrometry. Our precourse assessments identified weaknesses in student experience and knowledge in the fundamentals of mass spectrometry, supporting that it was a necessary area for improvement. We incorporated a laboratory experiment focused on tandem mass spectrometry and database searching into a preexisting mini-semester project devoted to identifying metabolites from medicinal plants. Implementation of the experiment allowed students to make more confident metabolite identifications, introduced them to a cutting-edge database analysis platform (GNPS: Global Natural Products Social Molecular Networking), and increased student experience and knowledge of mass spectrometry in addition to the principle of dereplication of samples derived from nature.