ArticleCell reports2022
Dysregulation of Streptococcus pneumoniae zinc homeostasis breaks ampicillin resistance in a pneumonia infection model.
Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Article
- Overcoming methicillin resistance in Staphylococcus aureus via metal ion disruption of bacterial metabolism.npj antimicrobials and resistance · 2026Article
- Preclinical Pharmacokinetics and Pharmacodynamics of Antibiotic Adjuvants.ACS infectious diseases · 2026Review
- Newly identified antimicrobial activity of an 8-hydroxyquinoline-based ionophore against multidrug-resistant Enterococcus faecium and Staphylococcus aureus.The Journal of antimicrobial chemotherapy · 2026Article
- Asymmetric envelope surface disposition of secreted protein YjbI controls bimodal antibiotic susceptibilities in C. crescentus.The EMBO journal · 2026Article
- Polymethyl methacrylate microplastics affect oral microbiota diversity andFrontiers in microbiology · 2026Article
- Disruption of zinc homeostasis reverses tigecycline resistance inFrontiers in cellular and infection microbiology · 2025Article
- Low temperatures do not impair the bacterial plasmid conjugation on poultry meat.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2024Article
- Resisting death by metal: metabolism and Cu/Zn homeostasis in bacteria.Emerging topics in life sciences · 2024Review
- Hfe Permease andACS infectious diseases · 2024Article
- The promise of copper ionophores as antimicrobials.Current opinion in microbiology · 2023Review
- Repurposing sunscreen as an antibiotic: zinc-activated avobenzone inhibits methicillin-resistant Staphylococcus aureus.Metallomics : integrated biometal science · 2023Article
- Chelator PBT2 Forms a Ternary CuInternational journal of molecular sciences · 2023Article
- A conserved zinc-binding site inProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Zinc acquisition and its contribution toFrontiers in cellular and infection microbiology · 2023Article
- Synthesis, characterization, and antibacterial activities of a heteroscorpionate derivative platinum complex against methicillin-resistantFrontiers in cellular and infection microbiology · 2023Article
- Biosynthesis of uridine diphosphate N-Acetylglucosamine: An underexploited pathway in the search for novel antibiotics?IUBMB life · 2022Review
- Metal Homeostasis in Pathogenic Streptococci.Microorganisms · 2022Review
- Neurodegenerative Disease Treatment Drug PBT2 Breaks Intrinsic Polymyxin Resistance in Gram-Positive Bacteria.Antibiotics (Basel, Switzerland) · 2022Article
- Gut microbiota contributes to the methionine metabolism in host.Frontiers in microbiology · 2022Article
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19 authors.
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Abstract
Streptococcus pneumoniae is the primary cause of community-acquired bacterial pneumonia with rates of penicillin and multidrug-resistance exceeding 80% and 40%, respectively. The innate immune response generates a variety of antimicrobial agents to control infection, including zinc stress. Here, we characterize the impact of zinc intoxication on S. pneumoniae, observing disruptions in central carbon metabolism, lipid biogenesis, and peptidoglycan biosynthesis. Characterization of the pivotal peptidoglycan biosynthetic enzyme GlmU indicates a sensitivity to zinc inhibition. Disruption of the sole zinc efflux pathway, czcD, renders S. pneumoniae highly susceptible to β-lactam antibiotics. To dysregulate zinc homeostasis in the wild-type strain, we investigated the safe-for-human-use ionophore 5,7-dichloro-2-[(dimethylamino)methyl]quinolin-8-ol (PBT2). PBT2 rendered wild-type S. pneumoniae strains sensitive to a range of antibiotics. Using an invasive ampicillin-resistant strain, we demonstrate in a murine pneumonia infection model the efficacy of PBT2 + ampicillin treatment. These findings present a therapeutic modality to break antibiotic resistance in multidrug-resistant S. pneumoniae.
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