Discovery of platencin, a dual FabF and FabH inhibitor with in vivo antibiotic properties
Year: 2007
Type: article
Abstract: Emergence of bacterial resistance is a major issue for all classes of antibiotics; therefore, the identification of new classes is critically needed. Recently we reported the discovery of platensimycin by screening natural product extracts using a target-based whole-cell strategy with antisense silencing technology in concert with cell free biochemical validations. Continued screening efforts led to the discovery of platencin, a novel natural product that is chemically and biologically related but different from platensimycin. Platencin exhibits a broad-spectrum Gram-positive antibacterial activity through inhibition of fatty acid biosynthesis. It does not exhibit cross-resistance to key antibiotic resistant strains tested, including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate S. aureus, and vancomycin-resistant Enterococci. Platencin shows potent in vivo efficacy without any observed toxicity. It targets two essential proteins, beta-ketoacyl-[acyl carrier protein (ACP)] synthase II (FabF) and III (FabH) with IC50 values of 1.95 and 3.91 microg/ml, respectively, whereas platensimycin targets only FabF (IC50 = 0.13 microg/ml) in S. aureus, emphasizing the fact that more antibiotics with novel structures and new modes of action can be discovered by using this antisense differential sensitivity whole-cell screening paradigm.
Authors: Jun Wang, Srinivas Kodali, Sang Ho Lee, Andrew Galgoci, Ronald Painter, Karen Dorso, Fred Racine, Mary Motyl, Lorraine Hernandez, Elizabeth Tinney, Steven L. Colletti, Kithsiri Herath, Richard Cummings, Oscar Salazar, Ignacio González, Angela Basilio, Francisca Vicente, Olga Genilloud, Fernando Pelaez, Hiranthi Jayasuriya, Katherine Young, Doris F. Cully, Sheo B. Singh
Language: English
Subfield: Applied Microbiology and Biotechnology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2042856986