ArticlePloS one2014
Extracellular zinc competitively inhibits manganese uptake and compromises oxidative stress management in Streptococcus pneumoniae.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
90 citing papers in PubMed, 136 citations in OpenAlex.
- The genes zntA and zntR encoding a P-type ATPase and its activator confer zinc and cadmium resistance in Chromobacterium violaceum.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Article
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- Fabrication of Chondroitin Sulfate-Copper/Zinc Complexes and Antibacterial Activity Involving Hydrogel Application in Infected Wound Healing.Gels (Basel, Switzerland) · 2026Article
- Zinc Tolerance Through Glutathione Import Strikes a Fine Balance Between Protection and Damage inbioRxiv : the preprint server for biology · 2026Article
- Combined metallomics and metabolomics reveal impact of metal homeostasis on biological pathways in C. elegans.Analytical and bioanalytical chemistry · 2026Article
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- Mechanisms and Therapeutic Potential of Nutritional Immunity.Pathogens (Basel, Switzerland) · 2026Review
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- ZntR is a critical regulator for zinc homeostasis and involved in pathogenicity inMicrobiology spectrum · 2025Article
- The global proteome ofFrontiers in cellular and infection microbiology · 2025Article
- The five homologous CiaR-controlled Ccn sRNAs of Streptococcus pneumoniae modulate Zn-resistance.PLoS pathogens · 2024Article
- The genesApplied and environmental microbiology · 2024Article
- An opportunistic pathogen under stress: how Group B Streptococcus responds to cytotoxic reactive species and conditions of metal ion imbalance to survive.FEMS microbiology reviews · 2024Review
- The five homologous CiaR-controlled Ccn sRNAs ofbioRxiv : the preprint server for biology · 2024Article
- Resisting death by metal: metabolism and Cu/Zn homeostasis in bacteria.Emerging topics in life sciences · 2024Review
- Hfe Permease andACS infectious diseases · 2024Article
- Impact of Difluoromethylornithine and AMXT 1501 on Gene Expression and Capsule Regulation inBiomolecules · 2024Article
- IntracellularFrontiers in microbiology · 2024Article
- The nutritional roles of zinc for immune system and COVID-19 patients.Frontiers in nutrition · 2024Review
30 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 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Streptococcus pneumoniae requires manganese for colonization of the human host, but the underlying molecular basis for this requirement has not been elucidated. Recently, it was shown that zinc could compromise manganese uptake and that zinc levels increased during infection by S. pneumoniae in all the niches that it colonized. Here we show, by quantitative means, that extracellular zinc acts in a dose dependent manner to competitively inhibit manganese uptake by S. pneumoniae, with an EC50 of 30.2 µM for zinc in cation-defined media. By exploiting the ability to directly manipulate S. pneumoniae accumulation of manganese, we analyzed the connection between manganese and superoxide dismutase (SodA), a primary source of protection for S. pneumoniae against oxidative stress. We show that manganese starvation led to a decrease in sodA transcription indicating that expression of sodA was regulated through an unknown manganese responsive pathway. Intriguingly, examination of recombinant SodA revealed that the enzyme was potentially a cambialistic superoxide dismutase with an iron/manganese cofactor. SodA was also shown to provide the majority of protection against oxidative stress as a S. pneumoniae ΔsodA mutant strain was found to be hypersensitive to oxidative stress, despite having wild-type manganese levels, indicating that the metal ion alone was not sufficiently protective. Collectively, these results provide a quantitative assessment of the competitive effect of zinc upon manganese uptake and provide a molecular basis for how extracellular zinc exerts a 'toxic' effect on bacterial pathogens, such as S. pneumoniae.
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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.