Each day, nearly 270 Americans die as a result of healthcare-associated infections costing patients and medical providers ~$5 billion per year in attributable medical expenses (1).  Healthcare-associated infections are caused by an assortment of bacteria and fungi that are contracted by patients in a variety of medical settings (e.g., clinics, hospitals, adult care facilities, etc.) (2-4).  Notably, many of the microorganisms responsible for healthcare-associated infections are distinguished by the likelihood that they have acquired resistance to one or more antimicrobials (2).  One of the research goals of our group is to identify and develop novel antibacterial and antifungal agents from natural sources.  We are particularly interested in examining fungi from diverse environments since this is a chemically diverse and understudied resource for obtaining new antimicrobial lead compounds.

The multitude of transcriptionally silent gene clusters in fungi represents an outstanding resource of new fungal natural products.  These silent gene clusters are thought to require elicitation from a variety of external stimuli whose identities and functions remain largely irreproducible under artificial laboratory culture conditions.  The Natural Products Discovery Group uses a chemical epigenetics-based approach that provides unparalleled access to novel antimicrobial metabolites from silenced biosynthetic pathways in fungi.  These efforts have provide a wealth of intriguing leads that are being actively pursued by our group.

References

1. Klevens, R., Edwards, J., Richards Jr., C., Horan, T., Gaynes, R., Pollock, D. and Cardo, D. (2007) Estimating health care-associated infections and deaths in U.S. hospitals, 2002. Public Health Reports, 122, 160-166.
2. Kollef, M.H., Napolitano, L.M., Solomkin, J.S., Wunderink, R.G., Bae, I.-G., Fowler, V.G., Balk, R.A., Stevens, D.L., Rahal, J.J., Shorr, A.F. et al. (2008) Health care-associated infection (HAI): a critical appraisal of the emerging threat – proceedings of the HAI Summit. Clinical Infectious Diseases, 47, S55-S99.
3. Diekema, D.J. (2007) Healthcare-associated fungal infections: beyond Candida and Aspergillus. Southern Medical Journal, 100, 130-131.
4. Boucher, H.W., Talbot, G.H., Bradley, J.S., Edwards, J.E., Gilbert, D., Rice, L.B., Scheld, M., Spellberg, B. and Bartlett, J. (2009) Bad bugs, no drugs: No ESKAPE!  An update from the Infectious Diseases Society of America. Clinical Infectious Diseases, 48, 1-12.