Journal: Cell chemical biology

Article Title: Antibiotic target discovery by integrated phenotypic and activity-based profiling of electrophilic fragments

doi: 10.1016/j.chembiol.2025.02.001

Figure Lengend Snippet: Relative bacterial growth was determined by normalizing the OD600 value to the DMSO control. (A) Growth inhibition screen in S. aureus (MSSA476). (B) Growth inhibition screen in V. cholerae (SAD30). Hits (relative growth ≤10%) are labeled in red.

Article Snippet: S. aureus MSSA476 , ATCC , BAA-1721.

Techniques: Control, Inhibition, Labeling

Journal: Cell chemical biology

Article Title: Antibiotic target discovery by integrated phenotypic and activity-based profiling of electrophilic fragments

doi: 10.1016/j.chembiol.2025.02.001

Figure Lengend Snippet: (A) Time-dependent killing of S. flexneri M90T by 10-F05 ( n = 2, mean ± SD). (B) Resistance development of S. flexneri M90T to 10-F05 and kanamycin during daily serial passaging with sub-MIC concentrations. (C) Resistance development of S. aureus MSSA476 to 10-F05 and methicillin during daily serial passaging with sub-MIC concentrations. (D) MIC fold change of the 10-F05-resistant S. aureus MSSA476 toward other classes of antibiotics. MIC values were reported in .

Article Snippet: S. aureus MSSA476 , ATCC , BAA-1721.

Techniques: Passaging

Journal: Cell chemical biology

Article Title: Antibiotic target discovery by integrated phenotypic and activity-based profiling of electrophilic fragments

doi: 10.1016/j.chembiol.2025.02.001

Figure Lengend Snippet: (A) Structural-based sequence alignment of FabH proteins from different bacteria species. BS, B. subtilis strain 168; SA, S. aureus MSSA476; EF, E. faecium ; PA, P. aeruginosa ATCC 15692; EC, E. coli K12; SF, S. flexneri M90T; En, Enterobacter sp. (strain 638); KP, K. pneumoniae subsp. pneumoniae ATCC 700721; VC, V. cholerae serotype O1; AB, A. baumannii NCGM 237. The conserved cysteines are highlighted with a red box. (B) Left, structure of a reported FabH inhibitor, platencin. Right, MIC fold change of 10-F05 and platencin tested in WT and 10-F05-resistant S. aureus (passage 19 from ). (C) Scheme for chemical genetic interaction. MIC shifts correspond to the target overexpression and knock-out. (D) YiiD bypasses FabH to generate acetoacetyl-ACP in E. coli . (E) MIC fold change of 10-F05 tested in target-overexpression E. coli strains (ASKA collection). (F) MIC fold change of 10-F05 tested in target knockout E. coli strains (Keio collection). >: No full growth inhibition was observed at the highest concentration tested, indicating that the real MIC was higher than the number reported here. (G) Plate 10 of Cys-library was rescreened in YiiD overexpressing E. coli (K12) strains at 25 µM. Triazole ring-conjugated chloromethyl ketone hits are labeled in red. Other hits are labeled in black.

Article Snippet: S. aureus MSSA476 , ATCC , BAA-1721.

Techniques: Sequencing, Bacteria, Over Expression, Knock-Out, Inhibition, Concentration Assay, Labeling

Journal: Cell chemical biology

Article Title: Antibiotic target discovery by integrated phenotypic and activity-based profiling of electrophilic fragments

doi: 10.1016/j.chembiol.2025.02.001

Figure Lengend Snippet: KEY RESOURCES TABLE

Article Snippet: S. aureus MSSA476 , ATCC , BAA-1721.

Techniques: Virus, Recombinant, Viability Assay, Luciferase, Reporter Assay, Reverse Transcription, SYBR Green Assay, Activity Assay, Mass Spectrometry, Drug discovery, Mutagenesis, Software