A mechanism of salt bridge-mediated resistance to FtsZ inhibitor PC190723 revealed by a cell-based screen.

Bacterial cell division proteins, especially the tubulin homologue FtsZ, have emerged as strong targets for developing new antibiotics. Here, we have utilized the fission yeast heterologous expression system to develop a cell-based assay to screen for small molecules that directly and specifically target the bacterial cell division protein FtsZ. The strategy also allows for simultaneous assessment of the toxicity of the drugs to eukaryotic yeast cells. As a proof-of-concept of the utility of this assay, we demonstrate the effect of the inhibitors sanguinarine, berberine, and PC190723 on FtsZ. Though sanguinarine and berberine affect FtsZ polymerization, they exert a toxic effect on the cells. Further, using this assay system, we show that PC190723 affects Helicobacter pylori FtsZ function and gain new insights into the molecular determinants of resistance to PC190723. On the basis of sequence and structural analysis and site-specific mutations, we demonstrate that the presence of salt bridge interactions between the central H7 helix and ß-strands S9 and S10 mediates resistance to PC190723 in FtsZ. The single-step in vivo cell-based assay using fission yeast enabled us to dissect the contribution of sequence-specific features of FtsZ and cell permeability effects associated with bacterial cell envelopes. Thus, our assay serves as a potent tool to rapidly identify novel compounds targeting polymeric bacterial cytoskeletal proteins like FtsZ to understand how they alter polymerization dynamics and address resistance determinants in targets.

RecipeDB: a resource for exploring recipes.

Cooking is the act of turning nature into the culture, which has enabled the advent of the omnivorous human diet. The cultural wisdom of processing raw ingredients into delicious dishes is embodied in their cuisines. Recipes thus are the cultural capsules that encode elaborate cooking protocols for evoking sensory satiation as well as providing nourishment. As we stand on the verge of an epidemic of diet-linked disorders, it is eminently important to investigate the culinary correlates of recipes to probe their association with sensory responses as well as consequences for nutrition and health. RecipeDB (https://cosylab.iiitd.edu.in/recipedb) is a structured compilation of recipes, ingredients and nutrition profiles interlinked with flavor profiles and health associations. The repertoire comprises of meticulous integration of 118 171 recipes from cuisines across the globe (6 continents, 26 geocultural regions and 74 countries), cooked using 268 processes (heat, cook, boil, simmer, bake, etc.), by blending over 20 262 diverse ingredients, which are further linked to their flavor molecules (FlavorDB), nutritional profiles (US Department of Agriculture) and empirical records of disease associations obtained from MEDLINE (DietRx). This resource is aimed at facilitating scientific explorations of the culinary space (recipe, ingredient, cooking processes/techniques, dietary styles, etc.) linked to taste (flavor profile) and health (nutrition and disease associations) attributes seeking for divergent applications. Database URL:  https://cosylab.iiitd.edu.in/recipedb.