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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
BACH1 promotes tissue necrosis and Mycobacterium tuberculosis susceptibility
Nature Microbiology, Year 2023
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Description
Oxidative stress triggers ferroptosis, a form of cellular necrosis characterized by iron-dependent lipid peroxidation, and has been implicated in Mycobacterium tuberculosis (Mtb) pathogenesis. We investigated whether Bach1, a transcription factor that represses multiple antioxidant genes, regulates host resistance to Mtb. We found that BACH1 expression is associated clinically with active pulmonary tuberculosis. Bach1 deletion in Mtb-infected mice increased glutathione levels and Gpx4 expression that inhibit lipid peroxidation. Bach1 −/− macrophages exhibited increased resistance to Mtb-induced cell death, while Mtb-infected Bach1-deficient mice displayed reduced bacterial loads, pulmonary necrosis and lipid peroxidation concurrent with increased survival. Single-cell RNA-seq analysis of lungs from Mtb-infected Bach1 −/− mice revealed an enrichment of genes associated with ferroptosis suppression. Bach1 depletion in Mtb-infected B6.Sst1S mice that display human-like necrotic lung pathology also markedly reduced necrosis and increased host resistance. These findings identify Bach1 as a key regulator of cellular and tissue necrosis and host resistance in Mtb infection. © 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
Authors & Co-Authors
Amaral, Eduardo Pinheiro
United States, Bethesda
National Institutes of Health Nih
Namasivayam, Sivaranjani
United States, Bethesda
National Institutes of Health Nih
Queiroz, Artur T. L.
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Hilligan, Kerry L.
United States, Bethesda
National Institutes of Health Nih
Aberman, Kate E.
United States, Bethesda
National Institutes of Health Nih
Fisher, Logan
United States, Bethesda
National Institutes of Health Nih
United States, New York
Weill Cornell Graduate School of Medical Sciences
Barbosa-Bomfim, Caio Cesar
United States, Bethesda
National Institutes of Health Nih
Kauffman, Keith D.
United States, Bethesda
National Institutes of Health Nih
Gazzinelli-Guimarães, Pedro Henrique
United States, Bethesda
National Institutes of Health Nih
Costa, Diego Luís
United States, Bethesda
National Institutes of Health Nih
Brazil, Sao Paulo
Universidade de São Paulo
Barreto-Duarte, Beatriz
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Brazil, Salvador
Universidade Salvador
Santana, Monique Freire
Brazil, Manaus
Fundação Centro de Controle de Oncologia do Estado do Amazonas
Brazil, Manaus
Universidade do Estado do Amazonas
Cordeiro-Santos, Marcelo
Brazil, Manaus
Universidade do Estado do Amazonas
Brazil, Manaus
Universidade Nilton Lins
Barber, Daniel L.
United States, Bethesda
National Institutes of Health Nih
Wilkinson, Robert J.
South Africa, Cape Town
Wellcome Centre for Infectious Diseases Research in Africa
United Kingdom, London
The Francis Crick Institute
United Kingdom, London
Imperial College London
Kramnik, Igor B.
United States, Boston
Boston University Chobanian & Avedisian School of Medicine
Scriba, Thomas J.
South Africa, Cape Town
University of Cape Town
Mayer-Barber, Katrin D.
United States, Bethesda
National Institutes of Health Nih
Andrade, Bruno B.
Brazil, Rio de Janeiro
Fundacao Oswaldo Cruz
Brazil, Salvador
Universidade Salvador
Brazil, Salvador
Universidade Federal da Bahia
Brazil, Salvador
Escola Bahiana de Medicina e Saúde Pública – Ebmsp
Brazil, Salvador
Faculdade de Tecnologia e Ciências Ftc
United States, Nashville
Vanderbilt University School of Medicine
Sher, Alan F.
United States, Bethesda
National Institutes of Health Nih
Statistics
Authors: 20
Affiliations: 19
Identifiers
Doi:
10.1038/s41564-023-01523-7
ISSN:
20585276