ArticleScientific reports2016
Novel high throughput pooled shRNA screening identifies NQO1 as a potential drug target for host directed therapy for tuberculosis.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- SH3PXD2B is the critical host factor promoting the entry of mycobacteria.Applied and environmental microbiology · 2026Article
- TBK1-NQO1 negative feedback loop regulates antiviral innate immunity.Cell communication and signaling : CCS · 2026Article
- Macrophage states and polarization duringFrontiers in cellular and infection microbiology · 2026Review
- Host-directed therapeutic targets in macrophages and their ligands against mycobacteria tuberculosis.Infection and immunity · 2025Review
- Mycobacterial PstP impairs host RNA alternative splicing by dephosphorylation of spliceosome RBMX at S189.iMetaOmics · 2025Article
- Cancer Cell's Achilles Heels: Considerations for Design of Anti-Cancer Drug Combinations.International journal of molecular sciences · 2024Article
- Impact of Mycobacterium tuberculosis Glycolipids on the CD4+ T Cell-Macrophage Immunological Synapse.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Druggable redox pathways against Mycobacterium abscessus in cystic fibrosis patient-derived airway organoids.PLoS pathogens · 2023Article
- Recruitment of the CoREST transcription repressor complexes by Nerve Growth factor IB-like receptor (Nurr1/NR4A2) mediates silencing of HIV in microglial cells.PLoS pathogens · 2022Article
- NQO1 Binds and Supports SIRT1 Function.Frontiers in pharmacology · 2021Article
- Identification of genes involved in the regulation of TERT in hepatocellular carcinoma.Cancer science · 2019Article
- Cell-based RNAi screening and high-content analysis in primary calvarian osteoblasts applied to identification of osteoblast differentiation regulators.Scientific reports · 2018Article
- Estrogen receptor-1 is a key regulator of HIV-1 latency that imparts gender-specific restrictions on the latent reservoir.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- HIV-1 infection of microglial cells in a reconstituted humanized mouse model and identification of compounds that selectively reverse HIV latency.Journal of neurovirology · 2018Article
- Multidimensional pooled shRNA screens in human THP-1 cells identify candidate modulators of macrophage polarization.PloS one · 2017Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
unlabelledChemical regulation of macrophage function is one key strategy for developing host-directed adjuvant therapies for tuberculosis (TB). A critical step to develop these therapies is the identification and characterization of specific macrophage molecules and pathways with a high potential to serve as drug targets. Using a barcoded lentivirus-based pooled short-hairpin RNA (shRNA) library combined with next generation sequencing, we identified 205 silenced host genes highly enriched in mycobacteria-resistant macrophages. Twenty-one of these "hits" belonged to the oxidoreductase functional category. NAD(P)H: quinone oxidoreductase 1 (NQO1) was the top oxidoreductase "hit". NQO1 expression was increased after mycobacterial infection, and NQO1 knockdown increased macrophage differentiation, NF-κB activation, and the secretion of pro-inflammatory cytokines TNF-α and IL-1β in response to infection. This suggests that mycobacteria hijacks NQO1 to down-regulate pro-inflammatory and anti-bacterial functions. The competitive inhibitor of NQO1 dicoumarol synergized with rifampin to promote intracellular killing of mycobacteria. Thus, NQO1 is a new host target in mycobacterial infection that could potentially be exploited to increase antibiotic efficacy in vivo. Our findings also suggest that pooled shRNA libraries could be valuable tools for genome-wide screening in the search for novel druggable host targets for adjunctive TB therapies.
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