There is a critical need to identify new antifungal drugs to deal with the rapid increase in invasive fungal pathogens that are resistant to existing antifungal agents. Associate Program 4 will help address this through the collaborative efforts of this ICBG. Specifically, we will couple a unique and highly efficient antifungal discovery platform with the natural product ICBG-created molecular libraries. A successful antimicrobial drug development program requires the ability to rapidly forecast the efficacy and safety of candidate compounds in humans. The goal of this screening and development project is to utilize high-throughput in vitro screens and select infection models with an established track record for projecting human antifungal therapy outcomes to identify novel antimicrobial natural product scaffolds from the ICBG collection. The UW Antimicrobial Testing Facility has extensive experience with clinically relevant in vitro and murine models for the drug-resistant fungal pathogens on which AP5 is focusing. Studies from this facility have frequently been used in FDA submissions. This Facility will perform both the primary, secondary and in vivo assays along with the pharmacological assays needed to select high-value antifungal drugs. In fact, the above UW facility has successfully utilized these tools to discern the clinical efficacy of more than 100 individual compounds, including more than a dozen that have progressed into clinical use. The Facility has designed a natural product compound progression plan to use efficacy and safety in these in vitro screen and clinically relevant in vivo models as an early decision point in lead optimization. AP4 will work closely with the other APs, especially AP2 and AP5, to test promising compounds that advance from AP1, AP2, and AP3 via a logical and progressive screening and development plan.

National Institute of Health (NIH)
Fogarty International Center (FIC)
Research Program--Cooperative Agreements (U19)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-BCMB-H (50))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Harvard Medical School
United States
Zip Code
Van Arnam, Ethan B; Currie, Cameron R; Clardy, Jon (2018) Defense contracts: molecular protection in insect-microbe symbioses. Chem Soc Rev 47:1638-1651
Silva-Junior, Eduardo A; Ruzzini, Antonio C; Paludo, Camila R et al. (2018) Pyrazines from bacteria and ants: convergent chemistry within an ecological niche. Sci Rep 8:2595
Li, Hongjie; Sosa-Calvo, Jeffrey; Horn, Heidi A et al. (2018) Convergent evolution of complex structures for ant-bacterial defensive symbiosis in fungus-farming ants. Proc Natl Acad Sci U S A 115:10720-10725
Paludo, Camila R; Menezes, Cristiano; Silva-Junior, Eduardo A et al. (2018) Stingless Bee Larvae Require Fungal Steroid to Pupate. Sci Rep 8:1122
Ortega, Humberto E; Batista Jr, João M; Melo, Weilan G P et al. (2017) Absolute Configurations of Griseorhodins A and C. Tetrahedron Lett 58:4721-4723
Ramadhar, Timothy R; Zheng, Shao-Liang; Chen, Yu-Sheng et al. (2017) The Crystalline Sponge Method: A Solvent-Based Strategy to Facilitate Noncovalent Ordered Trapping of Solid and Liquid Organic Compounds. CrystEngComm 19:4528-4534
Gemperline, Erin; Horn, Heidi A; DeLaney, Kellen et al. (2017) Imaging with Mass Spectrometry of Bacteria on the Exoskeleton of Fungus-Growing Ants. ACS Chem Biol 12:1980-1985
Wyche, Thomas P; Ruzzini, Antonio C; Schwab, Laura et al. (2017) Tryptorubin A: A Polycyclic Peptide from a Fungus-Derived Streptomycete. J Am Chem Soc 139:12899-12902
Adnani, Navid; Rajski, Scott R; Bugni, Tim S (2017) Symbiosis-inspired approaches to antibiotic discovery. Nat Prod Rep 34:784-814
Lewin, Gina R; Carlos, Camila; Chevrette, Marc G et al. (2016) Evolution and Ecology of Actinobacteria and Their Bioenergy Applications. Annu Rev Microbiol 70:235-54

Showing the most recent 10 out of 17 publications