Structure-based design of MptpB inhibitors that reduce multi-drug-resistant mycobacterium tuberculosis survival and infection burden in vivo
| العنوان: | Structure-based design of MptpB inhibitors that reduce multi-drug-resistant mycobacterium tuberculosis survival and infection burden in vivo |
|---|---|
| المؤلفون: | Eric J. Thomas, Barry N Kreiswith, Steven Park, Ajanta Chakraborty, Lydia Tabernero, Charis R Saville, Jennifer S. Cavet, Natalia Kurepina, Ana P G Silva, Clare F. Vickers, Maximiliano G. Gutierrez, Paulina Fernandez, David S. Perlin, Laura Schnettger, Yandi Naranjo, Miquel Pons |
| المساهمون: | Universitat de Barcelona |
| المصدر: | Recercat. Dipósit de la Recerca de Catalunya instname Dipòsit Digital de la UB Universidad de Barcelona |
| بيانات النشر: | American Chemical Society |
| مصطلحات موضوعية: | Male, Models, Molecular, 0301 basic medicine, Tuberculosis, Protein Conformation, medicine.drug_class, Tuberculosi, Guinea Pigs, Antibiotics, Antitubercular Agents, 01 natural sciences, Virulence factor, Microbiology, Mycobacterium tuberculosis, Structure-Activity Relationship, 03 medical and health sciences, Fosforilació, Bacterial Proteins, In vivo, Tuberculosis, Multidrug-Resistant, Drug Discovery, medicine, Animals, Multidrug-Resistant Mycobacterium tuberculosis, Phosphorylation, Molecular Structure, biology, 010405 organic chemistry, Chemistry, Macrophages, Antimicrobial, medicine.disease, biology.organism_classification, Drug Resistance, Multiple, 0104 chemical sciences, 3. Good health, 030104 developmental biology, Drug Design, Molecular Medicine, Structure based, Female, Protein Tyrosine Phosphatases |
| الوصف: | [Image: see text] Mycobacterium tuberculosis protein-tyrosine-phosphatase B (MptpB) is a secreted virulence factor that subverts antimicrobial activity in the host. We report here the structure-based design of selective MptpB inhibitors that reduce survival of multidrug-resistant tuberculosis strains in macrophages and enhance killing efficacy by first-line antibiotics. Monotherapy with an orally bioavailable MptpB inhibitor reduces infection burden in acute and chronic guinea pig models and improves the overall pathology. Our findings provide a new paradigm for tuberculosis treatment. |
| وصف الملف: | application/pdf |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fab372acc4fc0cd48b1bbd78ce3550b7Test http://hdl.handle.net/2445/138558Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fab372acc4fc0cd48b1bbd78ce3550b7 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |