PlateEditor: A web-based application for the management of multi-well plate layouts and associated data.

Multi-well plates are convenient tools to work with in biology experiments, as they allow the probing of multiple conditions in a compact and economic way. Although both free and commercial software exist for the definition of plate layout and management of plate data, we were looking for a more flexible solution, available anywhere, free from download, installation and licensing constraints. In this context, we created PlateEditor, a free web-based, client-side application allowing rapid creation of even complex layouts, including dose-response curves and multiple combination experiments for any plate format up to 1536 wells. PlateEditor also provides heatmap visualization and aggregation features to speed-up the process of data analysis and formatting for export in other application. Written in pure JavaScript, it is fully open-source, can be integrated in various workflows and has the potential to be extended with more functionalities in the future.

Discovery of thienothiazolocarboxamide analogues as novel anti-tubercular agent.

In order to identify anti-tubercular agents with a novel scaffold, commercial libraries of small organic compounds were screened against a fluorescent strain of Mycobacterium tuberculosis H37Rv, using a dual phenotypic assay. Compounds were assessed against bacteria replicating in broth medium, as well as inside macrophages, and thienothiazolocarboxamide (TTCA) scaffold was identified as hit in both assays, with submicromolar inhibitory concentrations. Derivatives of TTCA were further synthesized and evaluated for their inhibitory effects on M.tuberculosis H37Rv. In the present study we report the structure-activity relationship of these TTCA derivatives. Compounds 28, 32 and 42 displayed good anti-tubercular activities, as well as favorable ADME and PK properties. Compound 42 exhibited excellent oral bioavailability in mice with high distribution to lungs, within 1 h. It was found to be efficacious in a dose dependent manner in a murine model of M. tuberculosis infection. Hence, compound 42 is now under evaluation as a potential lead candidate for treatment of tuberculosis.

Construction of Mycobacterium tuberculosis cdd knockout and evaluation of invasion and growth in macrophages.

Cytidine deaminase (MtCDA), encoded by cdd gene (Rv3315c), is the only enzyme identified in nucleotide biosynthesis pathway of Mycobacterium tuberculosis that is able to recycle cytidine and deoxycytidine. An M. tuberculosis knockout strain for cdd gene was obtained by allelic replacement. Evaluation of mRNA expression validated cdd deletion and showed the absence of polar effect. MudPIT LC-MS/MS data indicated thymidine phosphorylase expression was decreased in knockout and complemented strains. The cdd disruption does not affect M. tuberculosis growth both in Mid- dlebrook 7H9 and in RAW 264.7 cells, which indicates that cdd is not important for macrophage invasion and virulence.