The CARB-X Portfolio of Nontraditional Antibacterial Products.

The growing prevalence of antibiotic-resistant bacterial pathogens and the lack of new medicines to treat the infections they cause remain a significant global threat. In recent years, this ongoing unmet need has encouraged more research groups to focus on the discovery and development of nontraditional antibacterial agents, ranging from anti-virulence strategies to bacteriophage and ways to modulate the microbiome. The Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) is a global nonprofit public-private partnership dedicated to accelerating antibacterial-related research. Importantly, the CARB-X portfolio supports a wide variety of novel and innovative nontraditional programs to help the global antibacterial research ecosystem understand the potential that these modalities can play in the management or prevention of serious infections. We describe here the breadth of the CARB-X pipeline of novel nontraditional products.

Screensaver: an open source lab information management system (LIMS) for high throughput screening facilities.

BACKGROUND: Shared-usage high throughput screening (HTS) facilities are becoming more common in academe as large-scale small molecule and genome-scale RNAi screening strategies are adopted for basic research purposes. These shared facilities require a unique informatics infrastructure that must not only provide access to and analysis of screening data, but must also manage the administrative and technical challenges associated with conducting numerous, interleaved screening efforts run by multiple independent research groups. RESULTS: We have developed Screensaver, a free, open source, web-based lab information management system (LIMS), to address the informatics needs of our small molecule and RNAi screening facility. Screensaver supports the storage and comparison of screening data sets, as well as the management of information about screens, screeners, libraries, and laboratory work requests. To our knowledge, Screensaver is one of the first applications to support the storage and analysis of data from both genome-scale RNAi screening projects and small molecule screening projects. CONCLUSIONS: The informatics and administrative needs of an HTS facility may be best managed by a single, integrated, web-accessible application such as Screensaver. Screensaver has proven useful in meeting the requirements of the ICCB-Longwood/NSRB Screening Facility at Harvard Medical School, and has provided similar benefits to other HTS facilities.

Construction of a mariner-based transposon for epitope-tagging and genomic targeting.

Mobile genetic elements are often employed for constructing gene fusions or to perform mutagenesis. mariner transposons are well-suited to such applications because of their low site specificity, in vitro activity, and exceptionally broad host range. This report describes a mariner-based method for rapidly creating a large number of insertion mutants that can be converted to in-frame epitope fusions in a single step. First, a mariner-based vector is used to deliver a FLP recombinase substrate randomly into a target molecule. Expression of the FLP recombinase is then induced to catalyse the excision of sequences flanked by FLP recombinase target recognition sites, leaving behind a triple-FLAG epitope. The reversibility of the excision event provides opportunities for using genomic targeting methods easily to create transcriptional or translational fusions to genes of interest.