The Discovery of a Novel Antibiotic Mechanism

HOBT (hydroxybenzotriazole), TBTU (o-benzotriazole-1-yl-1,1,3/3-tetramethyluronium tetrafluoroborate), /-PrjEtN, 0°C to rt, 62% (b) AcOH/HjO (9 1), Zn, 2h, rt, 67% (c) CHjClj, pentafluorophenol, EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide), 

MIC defines the smallest concentration of a chemical compound that is needed to prevent growth of bacteria in a standardized laboratory procedure. 

ADEP induces the CIpP-dependent degradation of FtsZ in bacterial cells. ADEP treatment of exponentially growing cells of S. aureus HG001 resulted in a decreased abundance of FtsZ over time, compared with the untreated control. Immunodetection of FtsZ was performed using a spedfic anti-FtsZ antibody. (Reprinted with permission from [7].) 

Forward chemical genetics approaches start with compounds that cause a particular phenotype in a biological system (e.g., ADEPs inhibit cell growth and trigger filamentation). Subsequently, the target of this small molecule and its mechanism of action are elucidated. Hence, the forward chemical genetics workflow is from compounds to gene. Usually, in vivo experiments are carried out ahead of in vitro experiments. 

Reverse chemical genetics approaches start with a known gene or protein target of interest of which it is known that alteration of its function causes a certain phenotype. Subsequently, a compound collection is screened to identify small molecules that bind the target and alter its function in the desired way. Hence, the reverse chemical genetics workflow is from gene to compounds. Usually, in vitro experiments are carried out ahead of in vivo experiments. 

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