Inhibition of CorA-Dependent Magnesium Homeostasis Is Cidal in Mycobacterium tuberculosis-Reference-Cited by-同舟云学术

Inhibition of CorA-Dependent Magnesium Homeostasis Is Cidal in Mycobacterium tuberculosis

Published:2019-10 Issue:10 Volume:63 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Park Yumi¹^ORCID,Ahn Yong-Mo¹,Jonnala Surendranadha¹,Oh Sangmi¹,Fisher Julia M.¹,Goodwin Michael B.¹,Ioerger Thomas R.²,Via Laura E.¹,Bayliss Tracy³,Green Simon R.³,Ray Peter C.³,Wyatt Paul G.³,Barry Clifton E.¹,Boshoff Helena I.¹

Affiliation:

1. Tuberculosis Research Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA

2. Department of Computer Science and Engineering, Texas A&M University, College Station, Texas, USA

3. Drug Discovery Unit, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom

Abstract

Mechanisms of magnesium homeostasis in Mycobacterium tuberculosis are poorly understood. Here, we describe the characterization of a pyrimidinetrione amide scaffold that disrupts magnesium homeostasis in the pathogen by direct binding to the CorA Mg 2+ /Co 2+ transporter. Mutations in domains of CorA that are predicted to regulate the pore opening in response to Mg 2+ ions conferred resistance to this scaffold.

Funder

HHS | National Institutes of Health

Foundation for the National Institutes of Health

Bill and Melinda Gates Foundation

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.01006-19

Reference28 articles.

1. Tuberculosis: Current state of knowledge: An Epilogue