Throughout her research career in infectious diseases, Dr. Beth Fuchs has endeavored to elucidate the genetic and physical traits that convey virulence to microbial pathogens and investigate host defenses that can combat these infections. The invertebrate hosts employed in her studies are the greater wax moth Galleria mellonella, and the nematode Caenorhabditis elegans. She has shown that these model systems can be useful in evaluating the genetic requirements for microbial virulence and biofilm formation, a condition that occurs within a host, allowing tissue invasion and drug resistance. Notably, the use of infection models has made high throughput, automated screening of antimicrobial compounds feasible. In particular, C. elegans are amenable to liquid handling, are small, and can be tested with minute quantities of compound in a short period of time. Dr. Fuchs’ work has identified a number of compounds with antimicrobial properties.
There is a significant need for new antimicrobial compounds, capable of providing therapeutic relief to drug resistant strains of bacteria or fungi. Using the in vivo C. elegans infection model for fungal or bacterial pathogens, she screened drug and small molecule libraries in search of compounds that prolong the survival of infected nematodes. Towards the identification of new antibiotics, Dr. Fuchs and her colleagues discovered compounds that inhibit methicillin-resistant Staphylococcus aureus, including FDA approved drugs: auranofin, closantel, niclosamide, oxyclozanide, and rafoxanide. Further, compounds were identified to inhibit the Gram-negative bacteria Acinetobacter baumannii using the in vivo infection models, finding a family of cecropin peptides that inhibited the bacteria by screening a library of insect-derived antimicrobial peptides. The identification of microbial inhibitory compounds has led her to further explore thioredoxin reductase as a potential drug target site.
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