Actinomycetes. We have completed the screening of 65,000 actinomycete fermention extracts from the Extract Collection of Useful Microorganisms (ECUM), at Myongji University in South Korea. In this collaboration ECUM performs fermentations and primary extractions and and the ITR does both the natural products chemistry as well as all of the biology. A small number of extracts were prioritized based on potency, selective toxicity, spectrum of activity and lack of cross resistance with TB strains resistant to rifamycins and aminoglycosides. Large scale re-fermentations have provided sufficient biomass to allow the isolation of a number of active principles with MICs below 1 ug/ml. Structural elucidation of these compounds is now in progress and will be followed by isolation in larger quantity and advanced in vitro and in vivo profiling. This project makes extensive use of high speed countercurrent chromatography using new techniques developed in the laboratory of Dr. Guido Pauli, an affiliate faculty member. This work is supported by a small grant from the Potts Memorial Foundation.
Fungi. We have an on-going collaboration with Mycosynthetix which holds a collection of 55,000 fungi. Over 15,000 cultures have been screened and hits have been subjected to several counterscreens, Initial fractionations are currently in progress.This work is supported by a NIH SBIR grant.
Mushrooms. We are involved with 2 small companies in the exploration of mushrooms for novel anti-TB agents. With LifePharms, led by a former Pfizer scientist, we have screened hundreds of extracts and partially purified fractions while the fractionations are performed by the company. This work is supported by an NIH SBIR grant. With Fungi Perfecti, founded by the well-known mycologist and visionary Paul Stamets, we are focusing on species of mushrooms used for treating TB centuries ago and we perform the natural products chemistry as well as the biological profiling. See the search for one such species in the Pacific Northwest.
Marine invertebrates. We have active collaborations with U. Mississippi, Georgia Tech University (supported by an International Cooperative Biodiversity Group grant), and the University of Puerto Rico. In all cases the natural products chemistry is done by the /partner institution and the biology at UIC.
Terrestrial plants. With respect to terrestrial plants, we continue to support selected projects that 1) use new approaches such as HSCCC or pre-fractionation for detecting the activity of minor components, 2) use abundant plant-based skeletons as starting material for semi-synthesis or 3) focus on ethnobotanicals, an approach that has yielded some interesting results. Among the latter is a project being conducted with an indigenous healer in Iquitos, Peru.
Essential oil volatiles for inhalation therapy. In an attempt to offer something to reduce the contagiousness of patients with extensively drug resistant tuberculosis (XDR-TB), we evaluated the volatile components of approximately 100 essential oils for in vitro anti-TB activity. Five oils with exceptional in vitro activity in a gaseous contact assay were prioritized and are now the subject of a bioassay-guided isolation of the active principle(s).