ArticleNature2015
Glutathione activates virulence gene expression of an intracellular pathogen.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers.
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Who cites it
161 citing papers in PubMed, 283 citations in OpenAlex.
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- Attenuated Bacteria-Based Tumor Therapy: Clinical Application Risks, Marketing Approval Restrictions, and Coping Strategies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Bacterial post-translational changes: the possible enigma of multidrug resistance.Archives of microbiology · 2026Review
- A Structure-Based Analysis of the Evolution of Transcription Factors of the FNR/CRP Family.Biomolecules · 2026Review
- Fighting the invader: strategies against intracellular bacteria.Frontiers in pharmacology · 2026Review
- Raman signatures ofFrontiers in microbiology · 2026Article
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- Listeriosis.Nature reviews. Disease primers · 2025Review
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- Defined roles for the Staphylococcus aureus POT transporter DtpT in di/tripeptide uptake and glutathione utilisation inside human macrophages.PLoS pathogens · 2025Article
- Methylglyoxal is an antibacterial effector produced by macrophages during infection.Cell host & microbe · 2025Article
- Host glutathione is required for Rickettsia parkeri cell division and intracellular survival.Nature communications · 2025Article
- Stress-dependent activation of themBio · 2025Article
- Phosphorylation State Dictates Bacterial Stressosome Assembly and Function.Research square · 2025Article
- Long-chain unsaturated free fatty acids reduce the host cell invasion ofFrontiers in cellular and infection microbiology · 2025Article
- C-di-AMP accumulation disrupts glutathione metabolism inInfection and immunity · 2024Article
- Differential stress responsiveness determines intraspecies virulence heterogeneity and host adaptation in Listeria monocytogenes.Nature microbiology · 2024Article
101 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Intracellular pathogens are responsible for much of the world-wide morbidity and mortality due to infectious diseases. To colonize their hosts successfully, pathogens must sense their environment and regulate virulence gene expression appropriately. Accordingly, on entry into mammalian cells, the facultative intracellular bacterial pathogen Listeria monocytogenes remodels its transcriptional program by activating the master virulence regulator PrfA. Here we show that bacterial and host-derived glutathione are required to activate PrfA. In this study a genetic selection led to the identification of a bacterial mutant in glutathione synthase that exhibited reduced virulence gene expression and was attenuated 150-fold in mice. Genome sequencing of suppressor mutants that arose spontaneously in vivo revealed a single nucleotide change in prfA that locks the protein in the active conformation (PrfA*) and completely bypassed the requirement for glutathione during infection. Biochemical and genetic studies support a model in which glutathione-dependent PrfA activation is mediated by allosteric binding of glutathione to PrfA. Whereas glutathione and other low-molecular-weight thiols have important roles in redox homeostasis in all forms of life, here we demonstrate that glutathione represents a critical signalling molecule that activates the virulence of an intracellular pathogen.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.