Whole-cell screen of fragment library identifies gut microbiota metabolite indole propionic acid as antitubercular

• Main Authors: Negatu, D.A, Liu, J.J.J, Zimmerman, M, Kaya, F, Dartois, V, Aldrich, C.C, Gengenbacher, M, Dicka, T
• Other Authors: MEDICINE
• Format: Article
• Published: American Society for Microbiology 2020
• Subjects: 2 (2,2,4,7 tetramethyl 1,2,3,4 tetrahydroquinolin 1 yl)ethan 1 ol hydrate; 2 (3 chlorophenoxy)ethanethioamide; 2 methyl 1h imidazole 4 carbothioamide; 2 methyl 1h indol 5 amine; 2,5 dimethyl 1 (2 thienylmethyl) 1 pyrrole 3 carboxylic acid; 3 (4 fuorophenyl) 5 (methylsulfanyl) 1h pyrazole; 4 (4 chlorophenoxy) 3,5 dimethyl 1 pyrazole; 5 (4 chlorophenyl) n,n,2 trimethyl 3 furamide; 5 phenylthiophene 2 carboxylic acid; 6 chloro 1 (1,4 diazepan 1 yl) 1,3 benzothiazole; 6 methyl 4 piperazino 2 (trifluoromethyl)quinoline; 6,7,8,9 tetrahydrodibenzo[b,d]furan 2 amine; 7 hydroxy 4 (trifluoromethyl) 2h chromen 2 one; beta carboline; carboxymethylcellulose; dimethyl sulfoxide; ethambutol; ethyl 2 amino 5 methyl 4 phenylthiophene 3 carboxylate; indolepropionic acid; isoniazid; isoquinoline 3 carboxylic acid; macrogol 400; methyl 3 hydroxy 1 benzothiophene 2 carboxylate; methyl isoquinoline 3 carboxylate; pyrazinamide; rifampicin; tuberculostatic agent; unclassified drug; unindexed drug; [2,2 bithiophene] 5 carboxylic acid; [6 (piperidin 1 yl)pyridin 2 yl]methanamine; propionic acid; propionic acid derivative; acute toxicity; animal experiment; animal model; animal tissue; antibacterial activity; antitubercular activity; area under the curve; Article; AUC (0-24 h); bacterial load; bactericidal activity; CC50; chemotherapy; controlled study; cytotoxicity; drug bioavailability; drug blood level; drug delivery system; drug determination; drug efficacy; drug half life; drug mechanism; drug potency; drug screening; drug tolerability; elimination rate constant; erythrocyte; Escherichia coli; female; growth inhibition; HC50; hemolysis; Hep-G2 cell line; human; human cell; hydrogen bond; in vitro study; in vivo study; intestine flora; limit of quantitation; lung tuberculosis; maximum concentration; MIC50; MIC90; molecular library; molecule; monotherapy; mouse; Mycobacterium abscessus; Mycobacterium smegmatis; Mycobacterium tuberculosis; nonhuman; partition coefficient; plasma concentration-time curve; priority journal; selectivity index; single drug dose; splenic tuberculosis; Staphylococcus aureus; THP-1 cell line; whole cell; animal; Bagg albino mouse; drug effect; microbial sensitivity test; Animals; Antitubercular Agents; Female; Gastrointestinal Microbiome; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Propionates; Pyrazinamide
• Online Access: https://scholarbank.nus.edu.sg/handle/10635/175122
• Institution: National University of Singapore

10.1128/AAC.01571-17