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The Mycophyte Discovery Group at UW-La Crosse is pioneering research in identifying novel antibiotics to combat chronic infections in cystic fibrosis (CF) patients. Utilizing an extensive library of wild mushroom species, our multidisciplinary team employs innovative screening techniques to isolate and synthesize active compounds. With the rise of antibiotic resistance, our mission focuses on finding effective treatments against pathogens like Pseudomonas aeruginosa and Burkholderia cepacia. Through collaboration and cutting-edge chemistry, we aim to improve the lives of CF patients.
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UW-L MYCOPHYTE DISCOVERY GROUP Chemistry Microbiology Biology Fighting Infection in Patients with Cystic Fibrosis Bill Schwan UW-La Crosse University of Wisconsin–La Crosse
Chemistry Microbiology Biology UW-L MYCO-PHYTE DISCOVERY GROUP a UW-La Crosse interdisciplinary initiative Chemistry Microbiology Biology University of Wisconsin–La Crosse
RELATIVELY RAPID (and inexpensive) MUCH SLOWER (and costly) UW-L MYCOPHYTE DISCOVERY GROUP General procedure: collect screen isolate screen elucidate synthesize derivatize screen screen screen Chemistry Microbiology Biology X inactive–stop X inactive–stop active partition & bioassay crude extract Isolate active cmpd(s) purify solve structure search literature protect IP myco / phyto active–go initial bioassay (other screens?) inactive–stop more bio (and tox) screens synthesis analogs protect IP pre-clinical studies clinical trials University of Wisconsin–La Crosse
Prof Tom Volk Biology, UW-L Prof Marc Rott Microbiology, UW-L Prof William Schwan Microbiology, UW-L Prof Aaron Monte Chemistry, UW-L Dr. Joe Toce Chemistry, UW-L Prof James Cook & M. S. Kabir Chemistry, UW-M Dr. Xueting Liu Chemistry, UW-L The WiSys Team: Mindy, Bill Maliyakal, Bethany, Lisa Jonathan Fritz, JD, MS, BS Whyte, Hirschboeck, & Dudek, S.C. MYCOPHYTE DISCOVERY UW-L the multidisciplinary team—these people and more! Chemistry Microbiology Biology University of Wisconsin–La Crosse
UW-L MYCOPHYTE DISCOVERY Chemistry Microbiology Biology progress / collaborative opportunities NOVEL ANALOGS PROJECT ACTIVITY STRUCTURE NOVEL? SYNTHESIS PRE-CLINICAL CLINICAL * + ~300 wild mushroom species with wide variety of activities… + ongoing collaborations w/ WI Native Americans / herbal remedies… COULD SHARE CRUDE EXTRACT LIBRARY TO SCREEN FOR ADDL ACTIVITIES NEED HELP HERE AND HERE! University of Wisconsin–La Crosse
UW-L MYCOPHYTE DISCOVERY GROUP Chemistry Microbiology Biology Project MD-2/F250 Screened fungal fruiting body library against bacteria that colonize the lungs of Cystic Fibrosis patients Goal: Find new antibiotic University of Wisconsin–La Crosse
UW-L MYCOPHYTE DISCOVERY GROUP Chemistry Microbiology Biology What is Cystic Fibrosis? www.nlm.nih.gov University of Wisconsin–La Crosse
UW-L MYCOPHYTE DISCOVERY GROUP Chemistry Microbiology Biology What is Cystic Fibrosis? • Homozygous recessive genetic disease • afflicting Caucasian individuals • Average lifespan of a CF patient is only 32 years • Characterized by chronic bronchial infections that • kill more than 90% of CF patients • Antibiotic resistance in the bacteria a big problem University of Wisconsin–La Crosse
UW-L MYCOPHYTE DISCOVERY GROUP Chemistry Microbiology Biology Screening Protocol • Screened a library of 260 fungal fruiting bodies • Used disk diffusion assays for screening • Target organisms were Pseudomonas aeruginosa • and Acinetobacter baumannii • Best hit was against fungus labeled F10/F250 • Expanded the assay to include • Burkholderia cepacia and • Stenotrophomonas maltophilia University of Wisconsin–La Crosse
UW-L MYCOPHYTE DISCOVERY GROUP Chemistry Microbiology Biology Disk Diffusion Assays Against Glucose Nonfermenting Gram-negative Rods University of Wisconsin–La Crosse
UW-L MYCOPHYTE DISCOVERY GROUP Chemistry Microbiology Biology Purification of the Active Drug • First, thin-layer chromatography • Second, HPLC separation of active peak • Elucidation of structure of active drug using • Mass Spectrometry • NMR Spectroscopy University of Wisconsin–La Crosse
UW-L MYCOPHYTE DISCOVERY GROUP Chemistry Microbiology Biology Structure of Active Natural Product Drug University of Wisconsin–La Crosse
UW-L MYCOPHYTE DISCOVERY GROUP Chemistry Microbiology Biology 2-AQ MICs Against Glucose Nonfermenting Gram-negative Rods University of Wisconsin–La Crosse
UW-L MYCOPHYTE DISCOVERY GROUP Chemistry Microbiology Biology What To Do Next? • Synthesize 2-AQ • Make analogs of 2-AQ • Proceed with pre-clinical testing of 2-AQ • More cytotoxicity testing in vitro • Safety testing in mice/rats • Efficacy testing in mice/rats University of Wisconsin–La Crosse
UW-L MYCOPHYTE DISCOVERY GROUP Chemistry Microbiology Biology Possible 2-AQ Analogs University of Wisconsin–La Crosse
UW-L MYCOPHYTE DISCOVERY GROUP Chemistry Microbiology Biology Synthetic Route #1 Merck Patent Approach University of Wisconsin–La Crosse
UW-L MYCOPHYTE DISCOVERY GROUP Chemistry Microbiology Biology Synthetic Route #2 Wittig-Style Approach University of Wisconsin–La Crosse
UW-L MYCOPHYTE DISCOVERY GROUP Chemistry Microbiology Biology Acknowledgements Mycophyte Discovery Co-Founders: Aaron Monte, Marc Rott, Joe Toce, Tom Volk UW-L Helpers: Craig Dunek, Kathleen Engelbrecht, Mike Gebhardt, Aaron McCoy, Ron McKelvey, Maria Drieta, Will Fiers, Nathan Connell Others: David Lewis, Jim Cook, Maliyakal John Monetary Assistance: UW-L, UW-System ARG and ARG-WiTAG grants University of Wisconsin–La Crosse
become a player in WI biotech? be the first startup in Western WI? …can it be done? UW-L MYCOPHYTE DISCOVERY business opportunities? Chemistry Microbiology Biology University of Wisconsin–La Crosse
