Planta Med 2013; 79 - PK12
DOI: 10.1055/s-0033-1348636

Optimized Marine Natural Products Discovery and Screening: Searching for Novel “Superbug” Antibiotics

V Macherla 1, M Hensler 2, H Houson 1, P Adhikari 1, W Thienphrapa 2, J Beverage 1, V Nizet 2, E Esquenazi 1
  • 1Sirenas Marine Discovery, 3550 General Atomics Ct., Bldg 02/211, San Diego, CA 92121
  • 2Department of Pediatrics and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093

The 2013 World Economic Forum Global Risks report proclaims antibiotic resistant bacteria to be one of the greatest and most far reaching global risks over the next ten years. Although de-emphasized over the last two decades, screening of natural products for novel antibiotics has a long, productive history. In this study we show that with combination of modern advances in mass spectrometry, metabolomics and high throughput isolation and screening, the search for novel antibiotics from marine organisms can be transformed to a fruitful and viable approach. In a span of seven months, 15 organisms yielded over 3500 fractions fully characterized by LC/MS/MS, of these 1100 had unique profiles with many above 80% purity. These 1100 fractions were subjected to metabolomic analysis as well as high-throughput screening against a panel of problematic pathogens including methicillin-resistant Staphylococcus aureus (MRSA). Several initial hits were verified in formal antibiotic susceptibility (MIC/MBC) testing, supporting the promise of the novel discovery platform.