Journal: Nature Communications

Article Title: Homo-BacPROTAC-induced degradation of ClpC1 as a strategy against drug-resistant mycobacteria

doi: 10.1038/s41467-024-46218-7

Figure Lengend Snippet: MICs of Homo-BacPROTACs and monomers against clinical isolates resistant to single Mtb drugs

Article Snippet: The different Mtb strains used were drug-sensitive strains (H37Rv ATCC 27294 and 11291), mono drug resistant strains Isoniazid resistant H37Rv (katG del ) ATCC 35822 , Rifampicin resistant H37Rv (rpoB S450L ) ATCC 35838 , moxifloxacin resistant H37Rv clinical isolate FNDR-M1 as well as multidrug resistant strains (ATCC 35825 and 8673) with drug-resistance against 1st and 2nd-line anti-TB drugs.

Techniques:

Journal: Nature Communications

Article Title: Homo-BacPROTAC-induced degradation of ClpC1 as a strategy against drug-resistant mycobacteria

doi: 10.1038/s41467-024-46218-7

Figure Lengend Snippet: a , b Exit vector 6-based Homo-BacPROTACs 7 and 8 (UdSBI-0545), as well as exit vector 7-based Homo-BacPROTACs 11 and 12 (UdSBI-4377) were assessed in a 4- and 7-day incubation on THP-1 macrophages following infection with Mtb H37Rv. The Homo-BacPROTACs were compared to their corresponding monomers ( 5 for exit vector 6 and 10 for exit vector 7) and the reference antibiotics rifampicin and moxifloxacin, which are known to inhibit the intracellular propagation of Mtb H37Rv. Exit vector 6 Homo-BacPROTACs showed a more efficient concentration-dependent reduction of cfu/ml over time with an E max of 1.22 − 1.27 at 50 µM, as compared to exit vector 7 based Homo-BacPROTACs or matched monomers. The various compound concentrations are indicated in different colours, matching across the panels. CC means Mtb culture control, where no drug treatment was given. For further details see text. Error bars indicate mean ± SD of n = 2 well replicates. The CC, rifampicin and moxifloxacin values were taken as common reference points in the various graphs. Source data are provided as a Source Data file.

Article Snippet: The different Mtb strains used were drug-sensitive strains (H37Rv ATCC 27294 and 11291), mono drug resistant strains Isoniazid resistant H37Rv (katG del ) ATCC 35822 , Rifampicin resistant H37Rv (rpoB S450L ) ATCC 35838 , moxifloxacin resistant H37Rv clinical isolate FNDR-M1 as well as multidrug resistant strains (ATCC 35825 and 8673) with drug-resistance against 1st and 2nd-line anti-TB drugs.

Techniques: Plasmid Preparation, Incubation, Infection, Concentration Assay, Control

Journal: Nature Communications

Article Title: Homo-BacPROTAC-induced degradation of ClpC1 as a strategy against drug-resistant mycobacteria

doi: 10.1038/s41467-024-46218-7

Figure Lengend Snippet: Structure-activity relationships of monomeric dCym derivatives and Homo-BacPROTACs

Article Snippet: The different Mtb strains used were drug-sensitive strains (H37Rv ATCC 27294 and 11291), mono drug resistant strains Isoniazid resistant H37Rv (katG del ) ATCC 35822 , Rifampicin resistant H37Rv (rpoB S450L ) ATCC 35838 , moxifloxacin resistant H37Rv clinical isolate FNDR-M1 as well as multidrug resistant strains (ATCC 35825 and 8673) with drug-resistance against 1st and 2nd-line anti-TB drugs.

Techniques: Permeability