Homo-BacPROTAC-induced degradation of ClpC1 as a strategy against drug-resistant mycobacteria.

Antimicrobial resistance is a global health threat that requires the development of new treatment concepts. These should not only overcome existing resistance but be designed to slow down the emergence of new resistance mechanisms. Targeted protein degradation, whereby a drug redirects cellular proteolytic machinery towards degrading a specific target, is an emerging concept in drug discovery.

Clp-targeting BacPROTACs impair mycobacterial proteostasis and survival.

The ClpC1:ClpP1P2 protease is a core component of the proteostasis system in mycobacteria. To improve the efficacy of antitubercular agents targeting the Clp protease, we characterized the mechanism of the antibiotics cyclomarin A and ecumicin. Quantitative proteomics revealed that the antibiotics cause massive proteome imbalances, including upregulation of two unannotated yet conserved stress response factors, ClpC2 and ClpC3.

The Update of the Italian Food Composition Database of Gluten-Free Products and Its Application in Food-Based Dietary Guidelines Menus.

Complete food composition databases (FCDBs) on gluten-free (GF) foods are needed to assess the nutrient intakes of celiac disease patients. The aim of the present work was to update the previously developed version of the Italian GF-FCDB and to apply it to a theoretical GF diet. The updated GF-FCDB includes the composition of 108 GF cereal-based foods, as sold, in terms of energy and macro- and micro-nutrients, imputed using food label information combined with the standard recipe approach.