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The pursuit of mechanism of action: uncovering drug complexity in TB drug discovery

Autor: Nicole S. Sampson, Tianao Yuan, Joshua M. Werman

Publikováno v: RSC Chem Biol

Whole cell-based phenotypic screens have become the primary mode of hit generation in tuberculosis (TB) drug discovery during the last two decades. Different drug screening models have been developed to mirror the complexity of TB disease in the labo

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::69a7fe10dad63ef7e4cf3e842d51ff74
https://doi.org/10.1039/d0cb00226g

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Post-translational Succinylation of Mycobacterium tuberculosis Enoyl-CoA Hydratase EchA19 Slows Catalytic Hydration of Cholesterol Catabolite 3-Oxo-chol-4,22-diene-24-oyl-CoA

Autor: Nicole S. Sampson, Rui Lu, Joshua M. Werman, Tianao Yuan, Natasha M. Nesbitt, Amber C. Bonds, Miguel Garcia-Diaz, Jungwon Jang

Publikováno v: ACS Infectious Diseases. 6:2214-2224

Cholesterol is a major carbon source for Mycobacterium tuberculosis (Mtb) during infection, and cholesterol utilization plays a significant role in persistence and virulence within host macrophages. Elucidating the mechanism by which cholesterol is d

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::b0df48c12d219c125ac94c350e63ecab
https://doi.org/10.1021/acsinfecdis.0c00329

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IpdE1-IpdE2 Is a Heterotetrameric Acyl Coenzyme A Dehydrogenase That Is Widely Distributed in Steroid-Degrading Bacteria

Autor: John E. Gadbery, Jie Liu, Israël Casabon, Nicole S. Sampson, Xinxin Yang, Lindsay D. Eltis, Tianao Yuan, James W. Round, Keith T Story, Matthew F. Wipperman, Adam M. Crowe

Publikováno v: Biochemistry

Steroid-degrading bacteria, including Mycobacterium tuberculosis (Mtb), utilize an architecturally distinct subfamily of acyl coenzyme A dehydrogenases (ACADs) for steroid catabolism. These ACADs are α2β2 heterotetramers that are usually encoded by

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c9c46afd01103899593f37a9c24fb299
https://doi.org/10.1021/acs.biochem.0c00005

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Reductive Power Generated by Mycobacterium leprae Through Cholesterol Oxidation Contributes to Lipid and ATP Synthesis

Autor: Patrick J. Brennan, Marcia Berrêdo-Pinho, Katherine Antunes de Mattos, Zachary DeBoard, Kelly Hutchins, Nicole S. Sampson, Georgia C. Atella, Maria Cristina Vidal Pessolani, Thabatta L. S. A. Rosa, John T. Belisle, Christine R Montague, Julio J. Amaral, Maria Angela M. Marques, Tianao Yuan, Patrícia Sammarco Rosa, Ramanuj Lahiri, Carlos Adriano A Silva, Brian C. VanderVen

Publikováno v: Frontiers in Cellular and Infection Microbiology, Vol 11 (2021)
Frontiers in Cellular and Infection Microbiology

Upon infection, Mycobacterium leprae, an obligate intracellular bacillus, induces accumulation of cholesterol-enriched lipid droplets (LDs) in Schwann cells (SCs). LDs are promptly recruited to M. leprae-containing phagosomes, and inhibition of this

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e825f5ea41804d2917ba785f768d5366
https://doi.org/10.3389/fcimb.2021.709972

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Mce3R Stress-Resistance Pathway Is Vulnerable to Small-Molecule Targeting That Improves Tuberculosis Drug Activities

Autor: Rui Ma, Nicole S. Sampson, Scott G. Franzblau, Harm van Bakel, Melissa Smith, Robert Sebra, Gintaras Deikus, Tianao Yuan, Kieran I. Chacko, Xinxin Yang, Andrew Kasarskis

Publikováno v: ACS Infectious Diseases. 5:1239-1251

[Image: see text] One-third of the world’s population carries Mycobacterium tuberculosis (Mtb), the infectious agent that causes tuberculosis (TB), and every 17 s someone dies of TB. After infection, Mtb can live dormant for decades in a granuloma

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3811109c65cb6c38b5f946d32ee3cc4c
https://doi.org/10.1021/acsinfecdis.9b00099

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Enzymatic β-Oxidation of the Cholesterol Side Chain in

Autor: Tianao, Yuan, Joshua M, Werman, Xingyu, Yin, Meng, Yang, Miguel, Garcia-Diaz, Nicole S, Sampson

Publikováno v: ACS Infectious Diseases

The unique ability of Mycobacterium tuberculosis (Mtb) to utilize host lipids such as cholesterol for survival, persistence, and virulence has made the metabolic pathway of cholesterol an area of great interest for therapeutics development. Herein, w

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=pmid________::b42e8425339854084f0330753f81df93
https://pubmed.ncbi.nlm.nih.gov/33826843

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Post-translational Succinylation of

Autor: Amber C, Bonds, Tianao, Yuan, Joshua M, Werman, Jungwon, Jang, Rui, Lu, Natasha M, Nesbitt, Miguel, Garcia-Diaz, Nicole S, Sampson

Publikováno v: ACS Infect Dis

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=pmid________::f7e6c0369fede26c6666c443ff0cac83
https://pubmed.ncbi.nlm.nih.gov/32649175

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Hit Generation in TB Drug Discovery: From Genome to Granuloma

Autor: Nicole S. Sampson, Tianao Yuan

Publikováno v: Chemical Reviews

Current tuberculosis (TB) drug development efforts are not sufficient to end the global TB epidemic. Recent efforts have focused on the development of whole-cell screening assays because biochemical, target-based inhibitor screens during the last two

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b205f56b8762c5159804bca9a8aa0faf
http://europepmc.org/articles/PMC5832989

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