High-Throughput Small Molecule Screening Reveals Structurally Diverse Compounds That Inhibit the Growth of Escherichia coli O157:H7 In Vitro
Abstract:Escherichia coli O157:H7 colonizes the gastrointestinal tract of ruminants asymptomatically and may enter the human food supply through fecal contamination. A fraction of individuals infected by E. coli O157:H7 develop hemolytic uremic syndrome, a life-threatening condition. When individuals infected by E. coli O157:H7 are treated with certain antibiotics, an increased incidence of hemolytic uremic syndrome may result. This finding supports the need to identify novel compounds that can either reduce the load of E. coli O157:H7 entering the human food supply or serve as alternative therapeutic treatments for infected individuals. We developed a high-throughput turbidometric assay to identify novel compounds that inhibit E. coli O157:H7 growth. Pin transfers were performed to introduce small molecule libraries into 384-well plates, where each well contained approximately 5.0 log CFU of E. coli O157:H7. Plates were incubated at 37°C for 18 h, and the optical density was measured to determine the effect of each small molecule. A total of 64,562 compounds were screened in duplicate, and 43 unique compounds inhibited E. coli O157:H7 growth. Thirty-eight of the 43 inhibitory compounds belonged to known bioactive libraries, and the other 5 compounds were from commercial libraries derived from splitting and pooling. Inhibitory compounds from known bioactive libraries were most frequently therapeutic antibiotics (n = 34) but also included an antiviral compound, a compound that disrupts the citric acid cycle, and two biguanide compounds, which have been used for various nonclinical applications. We identified two novel compounds (i.e., biguanides) that should be studied further for their ability to reduce pathogen populations in foods.
Document Type: Research Article
Affiliations: 1: Department of Animal Sciences, Colorado State University, Fort Collins, Colorado 80523, USA 2: Department of Animal Sciences, Colorado State University, Fort Collins, Colorado 80523, USA; Harris Ranch Beef Company, Selma, CA 93662, USA
Publication date: December 1, 2011
- IAFP Members with personal subscriptions to JFP Online: To access full-text JFP or JMFT articles, you must sign-in in the upper-right corner using your Ingenta sign-in details (your IAFP Member Login does not apply to this website). The Journal of Food Protection (JFP) is a refereed monthly publication. Each issue contains scientific research and authoritative review articles reporting on a variety of topics in food science pertaining to food safety and quality. The Journal is internationally recognized as the leading publication in the field of food microbiology with a readership exceeding 11,000 scientists from 70 countries. The Journal of Food Protection is indexed in Index Medicus, Current Contents, BIOSIS, PubMed, Medline, and many others.
Print and online subscriptions are available to IAFP Members and institutional subscribers. IAFP Members with a subscription to JFP Online will have access to all available JFP and JMFT content. Online visitors who are not IAFP Members or journal subscribers will be charged on a pay-per-view basis. Membership and subscription information is available at www.foodprotection.org.
- Information for Authors
- Submit a Paper
- Subscribe to this Title
- Membership Information
- Information for Advertisers
- Ingenta Connect is not responsible for the content or availability of external websites