ArticleNucleic acids research2019
Metal sensing and regulation of adaptive responses to manganese limitation by MtsR is critical for group A streptococcus virulence.
Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 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
14 citing papers in PubMed, 29 citations in OpenAlex.
- The conserved transcription factor PrlP modulates colonization and pathogenicity of Streptococcus suis in response to environmental stress.PLoS pathogens · 2025Article
- Bacterial Metallostasis: Metal Sensing, Metalloproteome Remodeling, and Metal Trafficking.Chemical reviews · 2024Review
- Manganese uptake by MtsABC contributes to the pathogenesis of human pathogen group A streptococcus by resisting host nutritional immune defenses.Infection and immunity · 2024Article
- Mis-regulation of Zn and Mn homeostasis is a key phenotype of Cu stress in Streptococcus pyogenes.Metallomics : integrated biometal science · 2023Article
- Manganese Efflux Achieved by MetA and MetB Affects Oxidative Stress Resistance and Iron Homeostasis in Riemerella anatipestifer.Applied and environmental microbiology · 2023Article
- Managing Manganese: The Role of Manganese Homeostasis in Streptococcal Pathogenesis.Frontiers in cell and developmental biology · 2022Review
- TroR Negatively Regulates the TroABCD System and Is Required for Resistance to Metal Toxicity and Virulence in Streptococcus suis.Applied and environmental microbiology · 2021Article
- The bacterial iron sensor IdeR recognizes its DNA targets by indirect readout.Nucleic acids research · 2021Article
- Bacterial iron detoxification at the molecular level.The Journal of biological chemistry · 2020Review
- Article
- Group A Streptococcus AdcR Regulon Participates in Bacterial Defense against Host-Mediated Zinc Sequestration and Contributes to Virulence.Infection and immunity · 2020Article
- Bacterial manganese sensing and homeostasis.Current opinion in chemical biology · 2020Review
- Allosteric control of metal-responsive transcriptional regulators in bacteria.The Journal of biological chemistry · 2020Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Pathogenic bacteria encounter host-imposed manganese (Mn) limitation during infection. Herein we report that in the human pathogen Streptococcus pyogenes, the adaptive response to Mn limitation is controlled by a DtxR family metalloregulator, MtsR. Genes upregulated by MtsR during Mn limitation include Mn (mtsABC) and Fe acquisition systems (sia operon), and a metal-independent DNA synthesis enzyme (nrdFEI.2). To elucidate the mechanism of metal sensing and gene regulation by MtsR, we determined the crystal structure of MtsR. MtsR employs two Mn-sensing sites to monitor metal availability, and metal occupancy at each site influences MtsR regulatory activity. The site 1 acts as the primary Mn sensing site, and loss of metal at site 1 causes robust upregulation of mtsABC. The vacant site 2 causes partial induction of mtsABC, indicating that site 2 functions as secondary Mn sensing site. Furthermore, we show that the C-terminal FeoA domains of adjacent dimers participate in the oligomerization of MtsR on DNA, and multimerization is critical for MtsR regulatory activity. Finally, the mtsR mutant strains defective in metal sensing and oligomerization are attenuated for virulence in a mouse model of invasive infection, indicating that Mn sensing and gene regulation by MtsR are critical processes during S. pyogenes infection.
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Registered trials
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