ArticlePLoS pathogens2021
Zinc limitation triggers anticipatory adaptations in Mycobacterium tuberculosis.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 52 citations in OpenAlex.
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- The accessory role of the outer membrane porin protein MspD inMicrobiology (Reading, England) · 2026Article
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- Alternative ribosome expression alone is insufficient to drive antibiotic tolerance inFrontiers in microbiology · 2026Article
- Transcript-Capture sequencing enriches mRNA ofNAR molecular medicine · 2026Article
- Genome graphs reveal the importance of structural variation in Mycobacterium tuberculosis evolution and drug resistance.Nature communications · 2025Article
- Forging biofilms: metal-induced microbial responses in biofilm formation.Journal of bacteriology · 2025Review
- Transcript-Capture sequencing enriches mRNA ofbioRxiv : the preprint server for biology · 2025Article
- Zinc Promotes Mitochondrial Health Through PGC-1alpha Enhancing Bacterial Clearance in Macrophages Infected withInternational journal of molecular sciences · 2025Article
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- Analysis of stress response in multiple bacterial pathogens using a network biology approach.Scientific reports · 2025Article
- Direct thin-layer agar for bedaquiline-susceptibility testing ofJournal of clinical microbiology · 2025Article
- Zinc-limitedInfection and immunity · 2025Article
- The mycobacterial ABC transporter IrtAB employs a membrane-facing crevice for siderophore-mediated iron uptake.Nature communications · 2025Article
- Synergistic antibacterial photodynamic therapy of lysine-porphyrin conjugate and metal ions combination againstFrontiers in pharmacology · 2025Article
- Impact of vitamin C deficiency on imaging patterns and ventilatory function in pulmonary tuberculosis.Frontiers in medicine · 2025Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Mycobacterium tuberculosis (Mtb) has complex and dynamic interactions with the human host, and subpopulations of Mtb that emerge during infection can influence disease outcomes. This study implicates zinc ion (Zn2+) availability as a likely driver of bacterial phenotypic heterogeneity in vivo. Zn2+ sequestration is part of "nutritional immunity", where the immune system limits micronutrients to control pathogen growth, but this defense mechanism seems to be ineffective in controlling Mtb infection. Nonetheless, Zn2+-limitation is an environmental cue sensed by Mtb, as calprotectin triggers the zinc uptake regulator (Zur) regulon response in vitro and co-localizes with Zn2+-limited Mtb in vivo. Prolonged Zn2+ limitation leads to numerous physiological changes in vitro, including differential expression of certain antigens, alterations in lipid metabolism and distinct cell surface morphology. Furthermore, Mtb enduring limited Zn2+ employ defensive measures to fight oxidative stress, by increasing expression of proteins involved in DNA repair and antioxidant activity, including well described virulence factors KatG and AhpC, along with altered utilization of redox cofactors. Here, we propose a model in which prolonged Zn2+ limitation defines a population of Mtb with anticipatory adaptations against impending immune attack, based on the evidence that Zn2+-limited Mtb are more resistant to oxidative stress and exhibit increased survival and induce more severe pulmonary granulomas in mice. Considering that extracellular Mtb may transit through the Zn2+-limited caseum before infecting naïve immune cells or upon host-to-host transmission, the resulting phenotypic heterogeneity driven by varied Zn2+ availability likely plays a key role during early interactions with host cells.
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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.