Andrea Stierle

Title : Further studies on a new family of Antibiotics produced by Cryptic biosynthesis in Extremophilic Fungi

Abstract:

According to the CDC, at least two million people are infected with antibiotic-resistant bacteria every year, and over 35,000 die annually as a direct result of these infections. The Infectious Disease Society of America published a policy report that outlined the consequences of the alarming rates of antibiotic resistance and the dire need for reinvestment in the search for new antibiotics to overcome the lean development pipeline. In 2017 the Stierle research lab reported a new class of fungal macrolide antibiotics produced in co-culture by two extremophilic fungi. These fungi were isolated from the Berkeley Pit, an acid mine waste lake in Butte, Montana, USA. Unlike canonical bacterial macrolide antibiotics, the berkeleylactones lack the sugar moieties responsible for both the activity and induced resistance associated with other classes of macrolide antibiotics. The berkeleylactones also have a unique mode of action. The lead compound, Berkeleylactone A, targets multi-drug resistant strains of Staphylococcus aureus and Bacillus anthracis with MIC values near 1 μg/mL. The berkeleylactones are undetectable in axenic cultures of the contributing fungi, which suggests that co-culture can elicit cryptic biosynthesis in participating organisms.
Efforts to determine the mode and mechanism of action of the berkeleylactones, to develop more potent analogues of this new class of antibiotics, and to assess their in vivo efficacy will be discussed.

Biography:

Dr. Andrea received her PhD in Organic Chemistry from Montana State University in 1988. She and her husband Don search for fungi growing in unusual environments as a source of new drug-like molecules that target diseases like cancer or stubborn bacterial infections. They have studied microbes from sponges living in the pristine waters of Bermuda and from yew trees from the temperate rain forests of the Pacific Northwest. In 1995, they began to explore the acidic, metal contaminated waters of the Berkeley Pit, a mine-waste lake in Butte, Montana. They discovered a rich microbiome and have mined these microbes for compounds with promising drug-like properties. They have found compounds that can block the metastatic spread of cancer cells, inflammation, and most recently, a new antibiotic that targets multi-drug resistant Staphylococcus aureus.