ArticleMolecular microbiology2017
The zinc efflux activator SczA protects Streptococcus pneumoniae serotype 2 D39 from intracellular zinc toxicity.
Article in Molecular microbiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 40 citations in OpenAlex.
- Article
- Review
- ZntR is a critical regulator for zinc homeostasis and involved in pathogenicity inMicrobiology spectrum · 2025Article
- Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking.Chemical reviews · 2024Review
- The five homologous CiaR-controlled Ccn sRNAs of Streptococcus pneumoniae modulate Zn-resistance.PLoS pathogens · 2024Article
- Calcium RescuesMicroorganisms · 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
- Activation of zinc uptake regulator by zinc binding to three regulatory sites.Nucleic acids research · 2024Article
- The five homologous CiaR-controlled Ccn sRNAs ofbioRxiv : the preprint server for biology · 2024Article
- Development of ZnSynthetic and systems biotechnology · 2024Article
- Structural basis of peptide secretion for Quorum sensing by ComA.Nature communications · 2023Article
- Negative regulation of MurZ and MurA underlies the essentiality of GpsB- and StkP-mediated protein phosphorylation in Streptococcus pneumoniae D39.Molecular microbiology · 2023Article
- Nutritional immunity: the battle for nutrient metals at the host-pathogen interface.Nature reviews. Microbiology · 2022Review
- ZccE is a Novel P-type ATPase That Protects Streptococcus mutans Against Zinc Intoxication.PLoS pathogens · 2022Article
- Bacterial Transcriptional Regulators: A Road Map for Functional, Structural, and Biophysical Characterization.International journal of molecular sciences · 2022Review
- Regulation of Bacterial Manganese Homeostasis and Usage During Stress Responses and Pathogenesis.Frontiers in molecular biosciences · 2022Review
- Cellular Mn/Zn Ratio Influences Phosphoglucomutase Activity and Capsule Production in Streptococcus pneumoniae D39.Journal of bacteriology · 2021Article
- Article
- Principles and practice of determining metal-protein affinities.The Biochemical journal · 2021Review
- Zinc: Multidimensional Effects on Living Organisms.Biomedicines · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Zinc is an essential trace element that serves as a catalytic cofactor in metalloenzymes and a structural element in proteins involved in general metabolism and cellular defenses of pathogenic bacteria. Despite its importance, high zinc levels can impair cellular processes, inhibiting growth of many pathogenic bacteria, including the major respiratory pathogen Streptococcus pneumoniae. Zinc intoxication is prevented in S. pneumoniae by expression of the zinc exporter CzcD, whose expression is activated by the novel TetR-family transcriptional zinc-sensing regulator SczA. How zinc bioavailability triggers activation of SczA is unknown. It is shown here through functional studies in S. pneumoniae that an unannotated homodimeric TetR from S. agalactiae (PDB 3KKC) is the bona fide zinc efflux regulator SczA, and binds two zinc ions per protomer. Mutagenesis analysis reveals two metal binding sites, termed A and B, located on opposite sides of the SczA C-terminal regulatory domain. In vivo, the A- and B-site SczA mutant variants impact S. pneumoniae resistance to zinc toxicity and survival in infected macrophages. A model is proposed for S. pneumoniae SczA function in which both A- and B-sites were required for transcriptional activation of czcD expression, with the A-site serving as the evolutionarily conserved intracellular sensing site in SczAs.
Indexed as
Identifiers
What OpenQuestion holds
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.