Natural products serve as critical drugs or drug precursors with broad pharmaceutical application, including serving as the most effective antibiotics. The widespread and rapid evolution of antibiotic-resistance in pathogenic microbes makes the discovery of novel therapeutics to treat infectious diseases of urgent importance. Despite this critical need, small molecule discovery has decreased substantially in recent decades and the pipeline of new antibiotics is rapidly diminishing. The broad goals of this project are to discover novel antibiotics with high therapeutic potential by identify new natural products from insect associated Actinobacteria (aim 1), using next-generation sequencing technology and bioinformatics to help discover novel compounds from symbiotic microbes (aim 2), and evaluating the natural products discovered in SAI and SA2 for their therapeutic potential (aim 3). Through its direct integration with the multidisciplinary team in the center, the work proposed holds the promise to generate numerous new drug leads with therapeutic potential, result in a new paradigm in drug discovery, and, by translation, to impact the treatment of drug-resistant infectious diseases on a global scale.
The emergence of antibiotic resistance in human pathogens represents a public health crisis. The goals of this project are to discover new antimicrobial drug leads from symbiotic Actinobacteria and to contribute to the development of genome-enabled approaches to drug discovery.
|Adnani, Navid; Rajski, Scott R; Bugni, Tim S (2017) Symbiosis-inspired approaches to antibiotic discovery. Nat Prod Rep 34:784-814|
|Lawry, Stephanie M; Tebbets, Brad; Kean, Iain et al. (2017) Fludioxonil Induces Drk1, a Fungal Group III Hybrid Histidine Kinase, To Dephosphorylate Its Downstream Target, Ypd1. Antimicrob Agents Chemother 61:|
|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|
|Mevers, Emily; Chouvenc, Thomas; Su, Nan-Yao et al. (2017) Chemical Interaction among Termite-Associated Microbes. J Chem Ecol 43:1078-1085|
|Zhang, Fan; Barns, Kenneth; Hoffmann, F Michael et al. (2017) Thalassosamide, a Siderophore Discovered from the Marine-Derived Bacterium Thalassospira profundimaris. J Nat Prod 80:2551-2555|
|Mevers, Emily; Saurí, Josep; Liu, Yizhou et al. (2016) Homodimericin A: A Complex Hexacyclic Fungal Metabolite. J Am Chem Soc 138:12324-7|
|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|
|Ruzzini, Antonio C; Clardy, Jon (2016) Gene Flow and Molecular Innovation in Bacteria. Curr Biol 26:R859-R864|
|Zhang, Yan; Adnani, Navid; Braun, Doug R et al. (2016) Micromonohalimanes A and B: Antibacterial Halimane-Type Diterpenoids from a Marine Micromonospora Species. J Nat Prod 79:2968-2972|
|Arango, R A; Carlson, C M; Currie, C R et al. (2016) Antimicrobial Activity of Actinobacteria Isolated From the Guts of Subterranean Termites. Environ Entomol 45:1415-1423|
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