Natural products, collectively known as small molecules that are biosynthesized by microorganisms, fungi and invertebrates, are engendered with diverse chemical structures that give rise to a broad range of biological activities. As such, natural products or their synthetic derivatives account for the majority of therapeutics currently in clinical use, especially among the antibiotic and antitumor drug classes. With the growing incidence of bacterial infections, many of which are caused by bacteria that are unaffected by standard antibiotic treatments (so-called drug-resistant bacteria), there is a particular need for basic and clinical research aimed at the discovery and development of new classes of antibiotics. With an emphasis on marine invertebrates as natural product source organisms, we have identified several classes of novel marine natural products that potently inhibit growth of wild type and drug-resistant pathogens, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium. Whole cell and in vitro assays have led to the hypothesis that one class of our recently reported antibiotics exerts its antibacterial activity through interactions with the bacterial cell division machinery, a validated target for antibiotic discovery. Ongoing studies in our laboratory include identification of the target/s of these novel antibiotics through an interdisciplinary approach involving chemical synthesis and whole cell localization and mechanistic studies. A long-term goal of this research includes identification of tractable lead compounds that can be used to treat bacterial infections caused by antibiotic-resistant bacteria.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$635,515
Indirect Cost
City
State
Country
Zip Code
Shi, Jingmin; Xie, Cen; Liu, Hongbing et al. (2016) Metabolism and Bioactivation of Fluorochloridone, a Novel Selective Herbicide, in Vivo and in Vitro. Environ Sci Technol 50:9652-60
Sclafani, Anthony; Koepsell, Hermann; Ackroff, Karen (2016) SGLT1 sugar transporter/sensor is required for post-oral glucose appetition. Am J Physiol Regul Integr Comp Physiol 310:R631-9
Sclafani, Anthony; Ackroff, Karen (2015) Advantame sweetener preference in C57BL/6J mice and Sprague-Dawley rats. Chem Senses 40:181-6
Sclafani, Anthony; Zukerman, Steven; Ackroff, Karen (2015) Postoral glucose sensing, not caloric content, determines sugar reward in C57BL/6J mice. Chem Senses 40:245-58
Acharya, Priyamvada; Lusvarghi, Sabrina; Bewley, Carole A et al. (2015) HIV-1 gp120 as a therapeutic target: navigating a moving labyrinth. Expert Opin Ther Targets 19:765-83
Lusvarghi, Sabrina; Ghirlando, Rodolfo; Wong, Chi-Huey et al. (2015) Glycopeptide mimetics recapitulate high-mannose-type oligosaccharide binding and function. Angew Chem Int Ed Engl 54:5603-8
Sastry, Mallika; Bewley, Carole A; Kwong, Peter D (2015) Effective isotope labeling of proteins in a mammalian expression system. Methods Enzymol 565:289-307
Vassilopoulos, Athanassios; Xiao, Cuiying; Chisholm, Cristine et al. (2014) Synergistic Therapeutic Effect of Cisplatin and Phosphatidylinositol 3-Kinase (PI3K) Inhibitors in Cancer Growth and Metastasis of Brca1 Mutant Tumors. J Biol Chem 289:24202-14
Sclafani, Anthony; Zukerman, Steven; Ackroff, Karen (2014) Fructose- and glucose-conditioned preferences in FVB mice: strain differences in post-oral sugar appetition. Am J Physiol Regul Integr Comp Physiol 307:R1448-57
Sclafani, Anthony; Ackroff, Karen (2014) Maltodextrin and fat preference deficits in ""taste-blind"" P2X2/P2X3 knockout mice. Chem Senses 39:507-14

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