أعرض في EDS

Structure-based design of MptpB inhibitors that reduce multi-drug-resistant mycobacterium tuberculosis survival and infection burden in vivo

التفاصيل البيبلوغرافية
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

ResultId	1
Header	edsair OpenAIRE edsair.doi.dedup.....fab372acc4fc0cd48b1bbd78ce3550b7 677 3 unknown 676.999938964844
PLink	https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsair&AN=edsair.doi.dedup.....fab372acc4fc0cd48b1bbd78ce3550b7&custid=s6537998&authtype=sso
FullText	Array ( [Availability] => 0 )
Items	Array ( [Name] => Title [Label] => Title [Group] => Ti [Data] => Structure-based design of MptpB inhibitors that reduce multi-drug-resistant mycobacterium tuberculosis survival and infection burden in vivo ) Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Eric+J%2E+Thomas%22">Eric J. Thomas</searchLink><br /><searchLink fieldCode="AR" term="%22Barry+N+Kreiswith%22">Barry N Kreiswith</searchLink><br /><searchLink fieldCode="AR" term="%22Steven+Park%22">Steven Park</searchLink><br /><searchLink fieldCode="AR" term="%22Ajanta+Chakraborty%22">Ajanta Chakraborty</searchLink><br /><searchLink fieldCode="AR" term="%22Lydia+Tabernero%22">Lydia Tabernero</searchLink><br /><searchLink fieldCode="AR" term="%22Charis+R+Saville%22">Charis R Saville</searchLink><br /><searchLink fieldCode="AR" term="%22Jennifer+S%2E+Cavet%22">Jennifer S. Cavet</searchLink><br /><searchLink fieldCode="AR" term="%22Natalia+Kurepina%22">Natalia Kurepina</searchLink><br /><searchLink fieldCode="AR" term="%22Ana+P+G+Silva%22">Ana P G Silva</searchLink><br /><searchLink fieldCode="AR" term="%22Clare+F%2E+Vickers%22">Clare F. Vickers</searchLink><br /><searchLink fieldCode="AR" term="%22Maximiliano+G%2E+Gutierrez%22">Maximiliano G. Gutierrez</searchLink><br /><searchLink fieldCode="AR" term="%22Paulina+Fernandez%22">Paulina Fernandez</searchLink><br /><searchLink fieldCode="AR" term="%22David+S%2E+Perlin%22">David S. Perlin</searchLink><br /><searchLink fieldCode="AR" term="%22Laura+Schnettger%22">Laura Schnettger</searchLink><br /><searchLink fieldCode="AR" term="%22Yandi+Naranjo%22">Yandi Naranjo</searchLink><br /><searchLink fieldCode="AR" term="%22Miquel+Pons%22">Miquel Pons</searchLink> ) Array ( [Name] => Author [Label] => Contributors [Group] => Au [Data] => Universitat de Barcelona ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => Recercat. Dipósit de la Recerca de Catalunya<br />instname<br />Dipòsit Digital de la UB<br />Universidad de Barcelona ) Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => American Chemical Society ) Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%22Male%22">Male</searchLink><br /><searchLink fieldCode="DE" term="%22Models%2C+Molecular%22">Models, Molecular</searchLink><br /><searchLink fieldCode="DE" term="%220301+basic+medicine%22">0301 basic medicine</searchLink><br /><searchLink fieldCode="DE" term="%22Tuberculosis%22">Tuberculosis</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+Conformation%22">Protein Conformation</searchLink><br /><searchLink fieldCode="DE" term="%22medicine%2Edrug%5Fclass%22">medicine.drug_class</searchLink><br /><searchLink fieldCode="DE" term="%22Tuberculosi%22">Tuberculosi</searchLink><br /><searchLink fieldCode="DE" term="%22Guinea+Pigs%22">Guinea Pigs</searchLink><br /><searchLink fieldCode="DE" term="%22Antibiotics%22">Antibiotics</searchLink><br /><searchLink fieldCode="DE" term="%22Antitubercular+Agents%22">Antitubercular Agents</searchLink><br /><searchLink fieldCode="DE" term="%2201+natural+sciences%22">01 natural sciences</searchLink><br /><searchLink fieldCode="DE" term="%22Virulence+factor%22">Virulence factor</searchLink><br /><searchLink fieldCode="DE" term="%22Microbiology%22">Microbiology</searchLink><br /><searchLink fieldCode="DE" term="%22Mycobacterium+tuberculosis%22">Mycobacterium tuberculosis</searchLink><br /><searchLink fieldCode="DE" term="%22Structure-Activity+Relationship%22">Structure-Activity Relationship</searchLink><br /><searchLink fieldCode="DE" term="%2203+medical+and+health+sciences%22">03 medical and health sciences</searchLink><br /><searchLink fieldCode="DE" term="%22Fosforilació%22">Fosforilació</searchLink><br /><searchLink fieldCode="DE" term="%22Bacterial+Proteins%22">Bacterial Proteins</searchLink><br /><searchLink fieldCode="DE" term="%22In+vivo%22">In vivo</searchLink><br /><searchLink fieldCode="DE" term="%22Tuberculosis%2C+Multidrug-Resistant%22">Tuberculosis, Multidrug-Resistant</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+Discovery%22">Drug Discovery</searchLink><br /><searchLink fieldCode="DE" term="%22medicine%22">medicine</searchLink><br /><searchLink fieldCode="DE" term="%22Animals%22">Animals</searchLink><br /><searchLink fieldCode="DE" term="%22Multidrug-Resistant+Mycobacterium+tuberculosis%22">Multidrug-Resistant Mycobacterium tuberculosis</searchLink><br /><searchLink fieldCode="DE" term="%22Phosphorylation%22">Phosphorylation</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+Structure%22">Molecular Structure</searchLink><br /><searchLink fieldCode="DE" term="%22biology%22">biology</searchLink><br /><searchLink fieldCode="DE" term="%22010405+organic+chemistry%22">010405 organic chemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Chemistry%22">Chemistry</searchLink><br /><searchLink fieldCode="DE" term="%22Macrophages%22">Macrophages</searchLink><br /><searchLink fieldCode="DE" term="%22Antimicrobial%22">Antimicrobial</searchLink><br /><searchLink fieldCode="DE" term="%22medicine%2Edisease%22">medicine.disease</searchLink><br /><searchLink fieldCode="DE" term="%22biology%2Eorganism%5Fclassification%22">biology.organism_classification</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+Resistance%2C+Multiple%22">Drug Resistance, Multiple</searchLink><br /><searchLink fieldCode="DE" term="%220104+chemical+sciences%22">0104 chemical sciences</searchLink><br /><searchLink fieldCode="DE" term="%223%2E+Good+health%22">3. Good health</searchLink><br /><searchLink fieldCode="DE" term="%22030104+developmental+biology%22">030104 developmental biology</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+Design%22">Drug Design</searchLink><br /><searchLink fieldCode="DE" term="%22Molecular+Medicine%22">Molecular Medicine</searchLink><br /><searchLink fieldCode="DE" term="%22Structure+based%22">Structure based</searchLink><br /><searchLink fieldCode="DE" term="%22Female%22">Female</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+Tyrosine+Phosphatases%22">Protein Tyrosine Phosphatases</searchLink> ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => [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. ) Array ( [Name] => Format [Label] => File Description [Group] => SrcInfo [Data] => application/pdf ) Array ( [Name] => URL [Label] => Access URL [Group] => URL [Data] => <link linkTarget="URL" linkTerm="https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fab372acc4fc0cd48b1bbd78ce3550b7" linkWindow="_blank">https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fab372acc4fc0cd48b1bbd78ce3550b7</link><br /><link linkTarget="URL" linkTerm="http://hdl.handle.net/2445/138558" linkWindow="_blank">http://hdl.handle.net/2445/138558</link> ) Array ( [Name] => Copyright [Label] => Rights [Group] => Cpyrght [Data] => OPEN ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsair.doi.dedup.....fab372acc4fc0cd48b1bbd78ce3550b7 )
RecordInfo	Array ( [BibEntity] => Array ( [Languages] => Array ( [0] => Array ( [Text] => Undetermined ) ) [Subjects] => Array ( [0] => Array ( [SubjectFull] => Male [Type] => general ) [1] => Array ( [SubjectFull] => Models, Molecular [Type] => general ) [2] => Array ( [SubjectFull] => 0301 basic medicine [Type] => general ) [3] => Array ( [SubjectFull] => Tuberculosis [Type] => general ) [4] => Array ( [SubjectFull] => Protein Conformation [Type] => general ) [5] => Array ( [SubjectFull] => medicine.drug_class [Type] => general ) [6] => Array ( [SubjectFull] => Tuberculosi [Type] => general ) [7] => Array ( [SubjectFull] => Guinea Pigs [Type] => general ) [8] => Array ( [SubjectFull] => Antibiotics [Type] => general ) [9] => Array ( [SubjectFull] => Antitubercular Agents [Type] => general ) [10] => Array ( [SubjectFull] => 01 natural sciences [Type] => general ) [11] => Array ( [SubjectFull] => Virulence factor [Type] => general ) [12] => Array ( [SubjectFull] => Microbiology [Type] => general ) [13] => Array ( [SubjectFull] => Mycobacterium tuberculosis [Type] => general ) [14] => Array ( [SubjectFull] => Structure-Activity Relationship [Type] => general ) [15] => Array ( [SubjectFull] => 03 medical and health sciences [Type] => general ) [16] => Array ( [SubjectFull] => Fosforilació [Type] => general ) [17] => Array ( [SubjectFull] => Bacterial Proteins [Type] => general ) [18] => Array ( [SubjectFull] => In vivo [Type] => general ) [19] => Array ( [SubjectFull] => Tuberculosis, Multidrug-Resistant [Type] => general ) [20] => Array ( [SubjectFull] => Drug Discovery [Type] => general ) [21] => Array ( [SubjectFull] => medicine [Type] => general ) [22] => Array ( [SubjectFull] => Animals [Type] => general ) [23] => Array ( [SubjectFull] => Multidrug-Resistant Mycobacterium tuberculosis [Type] => general ) [24] => Array ( [SubjectFull] => Phosphorylation [Type] => general ) [25] => Array ( [SubjectFull] => Molecular Structure [Type] => general ) [26] => Array ( [SubjectFull] => biology [Type] => general ) [27] => Array ( [SubjectFull] => 010405 organic chemistry [Type] => general ) [28] => Array ( [SubjectFull] => Chemistry [Type] => general ) [29] => Array ( [SubjectFull] => Macrophages [Type] => general ) [30] => Array ( [SubjectFull] => Antimicrobial [Type] => general ) [31] => Array ( [SubjectFull] => medicine.disease [Type] => general ) [32] => Array ( [SubjectFull] => biology.organism_classification [Type] => general ) [33] => Array ( [SubjectFull] => Drug Resistance, Multiple [Type] => general ) [34] => Array ( [SubjectFull] => 0104 chemical sciences [Type] => general ) [35] => Array ( [SubjectFull] => 3. Good health [Type] => general ) [36] => Array ( [SubjectFull] => 030104 developmental biology [Type] => general ) [37] => Array ( [SubjectFull] => Drug Design [Type] => general ) [38] => Array ( [SubjectFull] => Molecular Medicine [Type] => general ) [39] => Array ( [SubjectFull] => Structure based [Type] => general ) [40] => Array ( [SubjectFull] => Female [Type] => general ) [41] => Array ( [SubjectFull] => Protein Tyrosine Phosphatases [Type] => general ) ) [Titles] => Array ( [0] => Array ( [TitleFull] => Structure-based design of MptpB inhibitors that reduce multi-drug-resistant mycobacterium tuberculosis survival and infection burden in vivo [Type] => main ) ) ) [BibRelationships] => Array ( [HasContributorRelationships] => Array ( [0] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Eric J. Thomas ) ) ) [1] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Barry N Kreiswith ) ) ) [2] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Steven Park ) ) ) [3] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Ajanta Chakraborty ) ) ) [4] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Lydia Tabernero ) ) ) [5] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Charis R Saville ) ) ) [6] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Jennifer S. Cavet ) ) ) [7] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Natalia Kurepina ) ) ) [8] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Ana P G Silva ) ) ) [9] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Clare F. Vickers ) ) ) [10] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Maximiliano G. Gutierrez ) ) ) [11] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Paulina Fernandez ) ) ) [12] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => David S. Perlin ) ) ) [13] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Laura Schnettger ) ) ) [14] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Yandi Naranjo ) ) ) [15] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Miquel Pons ) ) ) [16] => Array ( [PersonEntity] => Array ( [Name] => Array ( [NameFull] => Universitat de Barcelona ) ) ) ) [IsPartOfRelationships] => Array ( [0] => Array ( [BibEntity] => Array ( [Identifiers] => Array ( [0] => Array ( [Type] => issn-locals [Value] => edsair ) [1] => Array ( [Type] => issn-locals [Value] => edsairFT ) ) ) ) ) ) )
IllustrationInfo