Sclerotiorin inhibits protein kinase G from Mycobacterium tuberculosis and impairs mycobacterial growth in macrophages

• Published in: Tuberculosis (Edinburgh, Scotland) Vol. 103; pp. 37 - 43
• Main Authors: Chen, Dongni, Ma, Shuangshuang, He, Lei, Yuan, Peibo, She, Zhigang, Lu, Yongjun
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.03.2017; Elsevier Science Ltd
• Subjects: Animals; Anti-tuberculosis; Antibiotics; Antitubercular Agents - chemistry; Antitubercular Agents - metabolism; Antitubercular Agents - pharmacology; Azaphilone; Bacterial Load; Bacterial Proteins - antagonists & inhibitors; Bacterial Proteins - chemistry; Bacterial Proteins - metabolism; Benzopyrans - chemistry; Benzopyrans - metabolism; Benzopyrans - pharmacology; Binding; Binding Sites; Catalysis; Cell culture; Cell survival; Cytotoxicity; Development strategies; Docking; Dose-Response Relationship, Drug; Drug development; Eukaryotes; Fungi; HeLa Cells; Humans; Infectious Disease; Inhibitors; Kinases; Macrophages; Macrophages - drug effects; Macrophages - microbiology; MCF-7 Cells; Mice; Molecular Docking Simulation; Molecular Targeted Therapy; Mycobacterium bovis - drug effects; Mycobacterium bovis - enzymology; Mycobacterium bovis - growth & development; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - enzymology; Mycobacterium tuberculosis - growth & development; Protein Binding; Protein Interaction Domains and Motifs; Protein kinase; Protein kinase G; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - metabolism; Protein Kinase Inhibitors - pharmacology; Protein-Serine-Threonine Kinases - antagonists & inhibitors; Protein-Serine-Threonine Kinases - chemistry; Protein-Serine-Threonine Kinases - metabolism; Proteins; Pulmonary/Respiratory; Rifampin; Survival; Toxicity; Tuberculosis; Tuberculosis - drug therapy; Tuberculosis - microbiology; Viability; Azaphilone; Inhibitors; Macrophages; Anti-tuberculosis; Protein kinase G

As a eukaryotic-like Ser/Thr protein kinase, Mycobacterium tuberculosis virulent effector protein kinase G (PknG) mediates mycobacterial survival by regulating bacterial cell metabolic processes and preventing phagosome-lysosome fusion in host macrophages. Targeting PknG is an effective strategy for...