New Tuberculosis Antibiotics from Filamentous Fungi

DESCRIPTION (provided by applicant): Approximately one third of the world's population is infected with the bacterium which causes tuberculosis (TB); one tenth of these will develop active TB. The current treatment for TB is complex and lengthy involving a cocktail of antibacterial agents. Patients who are co-infected with HIV convert to the active form of TB more readily, with the medicines for each disease interacting poorly. Drug resistant TB has emerged and spread; MDR-TB and XDR-TB are extremely difficult to cure. New medicines are urgently needed to combat this disease. Mycosynthetix owns a collection of approximately 55,000 filamentous fungi which were collected from around the world; these organisms have been used in discovery programs as a source for potential new medicines for a variety of diseases and as agricultural pesticides. In a preliminary study with the Institute for TB Research at the University of Illinois approximately 12,000 fungal samples have been tested for anti TB activity; a number of fungi have been shown to inhibit the growth of TB without effecting mammalian cells. This Phase I SBIR project is a proof of principle study which will investigate these lead cultures and prioritize them. In this study the lead fungi will be cultured using a variety of traditional and innovative culturing techniques with a goal of producing highly active cultures for further evaluation. In addition fermentation techniques involving the use of membrane supports will be evaluated as a method for producing active extracts containing minimal media components; this may introduce the possibility of simplifying the production process resulting in an inexpensive and therefore widely available medicine. Finally the three most promising fungi will be the subjects of a more extensive chemical and pharmacological evaluation to be conducted in a Phase II project. PUBLIC HEALTH RELEVANCE: TB infects approximately 2 billion people; because of complex regimes for treatment, which are made more complicated by HIV and HIV medicines, and the emergence of multiply drug resistant TB types (MDR-TB, XDR-TB) new drugs are urgently needed. In collaboration with the Institute for TB Research at the University of Illinois, Mycosynthetix has identified filamentous fungi collected from around the world which produce anti TB compounds. This project is a proof of concept that these fungal metabolites can form the basis for new medicines for TB.