ArticlePLoS pathogens2011
A molecular mechanism for bacterial susceptibility to zinc.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 210 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
210 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Immune Tolerance vs. Immune Resistance: The Interaction Between Host and Pathogens in Infectious Diseases.Frontiers in veterinary science · 2022Pooled it
- A Zur-dependent regulatory RNA involved in maintaining zinc homeostasis in Staphylococcus aureus.Nucleic acids research · 2026Article
- Printing to Fight Antimicrobial Resistance Through Nano/Microstructured Platforms.Chemical record (New York, N.Y.) · 2026Review
- Zinc tolerance through glutathione import strikes a fine balance between protection and damage inMicrobiology (Reading, England) · 2026Article
- Fabrication of Chondroitin Sulfate-Copper/Zinc Complexes and Antibacterial Activity Involving Hydrogel Application in Infected Wound Healing.Gels (Basel, Switzerland) · 2026Article
- Investigating synovial trace elements as diagnostic markers in acute septic arthritis: an exploratory study.Clinical rheumatology · 2026Article
- Biodegradable Zn-Based Implants: Progress, Challenges, and Pathways toward Clinical Translation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Overcoming methicillin resistance in Staphylococcus aureus via metal ion disruption of bacterial metabolism.npj antimicrobials and resistance · 2026Article
- Unveiling hidden microbial diversity in Mars 2020 mission assembly cleanrooms with molecular insights into the persistence and perseverance of novel species defying metagenome sequencing.Microbiology spectrum · 2026Article
- Zinc Tolerance Through Glutathione Import Strikes a Fine Balance Between Protection and Damage inbioRxiv : the preprint server for biology · 2026Article
- Article
- Mechanisms and Therapeutic Potential of Nutritional Immunity.Pathogens (Basel, Switzerland) · 2026Review
- Clostridium beijerinckii displays a soluble [FeFe]-hydrogenase/formate dehydrogenase enzyme complex that links H2 and CO2 metabolism.The Biochemical journal · 2026Article
- MerR-type regulator ZccR links zinc homeostasis to biofilm formation and interspecies competition inFrontiers in cellular and infection microbiology · 2026Article
- Microbial metal physiology: ions to ecosystems.Nature reviews. Microbiology · 2025Review
- Forging biofilms: metal-induced microbial responses in biofilm formation.Journal of bacteriology · 2025Review
- The pentose phosphate pathway is essential for the resistance of Gluconacetobacter diazotrophicus PAL5 to zinc.World journal of microbiology & biotechnology · 2025Article
- When less is more: Counterintuitive stoichiometries and cellular abundances are essential for ABC transporters' function.Science advances · 2025Article
- Systematic Model Peptide Studies: A Crucial Step To Understand the Coordination Chemistry of Mn(II) and Fe(II) in Proteins.Inorganic chemistry · 2025Article
- Computational and experimental mapping of the allosteric network of two manganese ABC transporters.Protein science : a publication of the Protein Society · 2025Article
150 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transition row metal ions are both essential and toxic to microorganisms. Zinc in excess has significant toxicity to bacteria, and host release of Zn(II) at mucosal surfaces is an important innate defence mechanism. However, the molecular mechanisms by which Zn(II) affords protection have not been defined. We show that in Streptococcus pneumoniae extracellular Zn(II) inhibits the acquisition of the essential metal Mn(II) by competing for binding to the solute binding protein PsaA. We show that, although Mn(II) is the high-affinity substrate for PsaA, Zn(II) can still bind, albeit with a difference in affinity of nearly two orders of magnitude. Despite the difference in metal ion affinities, high-resolution structures of PsaA in complex with Mn(II) or Zn(II) showed almost no difference. However, Zn(II)-PsaA is significantly more thermally stable than Mn(II)-PsaA, suggesting that Zn(II) binding may be irreversible. In vitro growth analyses show that extracellular Zn(II) is able to inhibit Mn(II) intracellular accumulation with little effect on intracellular Zn(II). The phenotype of S. pneumoniae grown at high Zn(II):Mn(II) ratios, i.e. induced Mn(II) starvation, closely mimicked a ΔpsaA mutant, which is unable to accumulate Mn(II). S. pneumoniae infection in vivo elicits massive elevation of the Zn(II):Mn(II) ratio and, in vitro, these Zn(II):Mn(II) ratios inhibited growth due to Mn(II) starvation, resulting in heightened sensitivity to oxidative stress and polymorphonuclear leucocyte killing. These results demonstrate that microbial susceptibility to Zn(II) toxicity is mediated by extracellular cation competition and that this can be harnessed by the innate immune response.
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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.