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Journal: BMC Microbiology
Article Title: Zinc pyrithione impairs iron-sulfur cluster biogenesis in Mycobacterium tuberculosis
doi: 10.1186/s12866-025-04644-7
Figure Lengend Snippet: ZnPT exhibits potent anti-tubercular activity. A Intracellular activity of ZnPT against Mtb H37Rv in macrophages. J774A.1 macrophages infected with Mtb H37Rv were treated with ZnPT at 0.5, 1.0, and 2.0 µg/mL for 72 h. B Time-kill kinetics of ZnPT in 7H9 medium. C Time-kill kinetics of ZnPT in 7H9 medium supplemented with 50 µg/mL BCS. Conducted in parallel with panel B. D Time-kill kinetics of ZnPT in Sauton medium. The experimental conditions matched panel B, but were conducted in copper-limiting Sauton medium. E Time-kill kinetics of ZnPT in Sauton medium supplemented with 5 µM CuSO 4 . Conducted in parallel with panel D. F ICP-MS quantification of intracellular copper levels. H37Rv cultures were treated with ZnPT (0.015 µg/mL; 0.03 µg/mL) or with elesclomol (0.5 µg/mL) for 4 h. Data are presented as the mean ± SD of three biological replicates. Statistical significance was determined using one-way ANOVA with Dunnett’s test (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001)
Article Snippet: Anti-Bacterial Compound Library (TargetMol, batch no. L4520),
Techniques: Activity Assay, Infection
Journal: BMC Microbiology
Article Title: Zinc pyrithione impairs iron-sulfur cluster biogenesis in Mycobacterium tuberculosis
doi: 10.1186/s12866-025-04644-7
Figure Lengend Snippet: Transcriptional reprogramming in Mtb induced by ZnPT exposure. Volcano plot of DEGs after 4 h ( A ) and 24 h ( B ) ZnPT exposure. C Copper ion stress response genes. D Sulfur metabolism. E SUF system. F siderophore biosynthesis. G Iron-sulfur proteins related to intermediary metabolism and respiration (selected based on functional relevance; not all genes showed significant differential expression). H Transcription, translation, post-translational modification. RNA-seq was performed in biological triplicate ( n = 3). C , D , E , F and H display genes with statistically significant differential expression (log 2 FC ≥ 1)
Article Snippet: Anti-Bacterial Compound Library (TargetMol, batch no. L4520),
Techniques: Functional Assay, Quantitative Proteomics, Modification, RNA Sequencing
Journal: BMC Microbiology
Article Title: Zinc pyrithione impairs iron-sulfur cluster biogenesis in Mycobacterium tuberculosis
doi: 10.1186/s12866-025-04644-7
Figure Lengend Snippet: Validation by RT-qPCR of transcriptional changes. A SUF operon induction under ZnPT stress. SUF genes ( Rv1460 - Rv1466 ) were upregulated after 4 and 24 h of exposure to 0.015 and 0.03 µg/mL. Fold-change values are normalized to untreated controls. B Dose-dependent gene expression responses to ZnPT at 24 h. There was a dose-dependent upregulation of ctpV (copper efflux), iscS (Fe-S biogenesis), furA (iron regulation), cysK2 (cysteine synthesis), and the Fe-S enzyme frdB (metabolism). Additionally, acn (metabolism) was downregulated. Data are presented herein as the mean ± SD of three biological replicates. Statistical significance was performed using two-way ANOVA with Dunnett’s test (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001)
Article Snippet: Anti-Bacterial Compound Library (TargetMol, batch no. L4520),
Techniques: Biomarker Discovery, Quantitative RT-PCR, Gene Expression
Journal: BMC Microbiology
Article Title: Zinc pyrithione impairs iron-sulfur cluster biogenesis in Mycobacterium tuberculosis
doi: 10.1186/s12866-025-04644-7
Figure Lengend Snippet: ZnPT inhibits the activities of cysteine desulfurase and Fe-S enzymes. A Cysteine desulfurase activity assay. Enzyme activity was measured by quantifying sulfide release from L-cysteine via methylene blue absorbance (670 nm), 10 µM TPEN serving as a positive control. B Aconitase activity. The iron chelator 2,2’-bipyridyl (BPY, 250 µM) was used as a positive control. C Succinate dehydrogenase activity. The SDH inhibitor 3-nitropropionic acid (3-NP, 100 µM) was employed as a positive control. Data are presented as the mean ± SD of three biological replicates. Statistical significance was determined using two-way ANOVA with Dunnett’s test (* p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001 vs. DMSO)
Article Snippet: Anti-Bacterial Compound Library (TargetMol, batch no. L4520),
Techniques: Activity Assay, Positive Control
Journal: BMC Microbiology
Article Title: Zinc pyrithione impairs iron-sulfur cluster biogenesis in Mycobacterium tuberculosis
doi: 10.1186/s12866-025-04644-7
Figure Lengend Snippet: ZnPT disrupts energy metabolism in Mtb . A Volcano plot of differential metabolites after ZnPT treatment. Energy metabolism-associated metabolites are highlighted. B Quantification of TCA cycle intermediates and glyoxylate shunt metabolites in response to ZnPT treatment. The metabolites analyzed include citrate, cis-aconitate, isocitrate, α-ketoglutarate, succinate, and glyoxylate (glyoxylate shunt). Data are presented as the mean ± SD of three biological replicates. C KEGG pathway enrichment analysis presented as a bubble plot, emphasizing pathways related to central carbon metabolism. D KEGG pathway classification of the identified metabolites. Statistical significance was determined using Student’s t-test or Welch’s t-test (for heterogeneous variances) (* p < 0.05 and ** p < 0.01 vs. DMSO)
Article Snippet: Anti-Bacterial Compound Library (TargetMol, batch no. L4520),
Techniques:
Journal: BMC Microbiology
Article Title: Zinc pyrithione impairs iron-sulfur cluster biogenesis in Mycobacterium tuberculosis
doi: 10.1186/s12866-025-04644-7
Figure Lengend Snippet: ZnPT disrupts the proton motive force and reduces ATP levels in Mtb . A ZnPT-induced PMF dissipation. PMF was assessed using the fluorescent probe BCECF-AM (15 µM) after 24 h treatment with ZnPT. The protonophore CCCP (15 µM) served as a positive control. B Dose-dependent reduction of ATP. ATP levels were quantified after 24 h exposure to ZnPT, with bedaquiline (BDQ, 0.24 µg/mL) serving as a positive control. Data normalized to total protein and expressed as a percentage of untreated controls. Results were presented as the mean ± SD of three biological replicates. Statistical significance was determined using one-way ANOVA with Dunnett’s test (**** p < 0.0001 vs. DMSO)
Article Snippet: Anti-Bacterial Compound Library (TargetMol, batch no. L4520),
Techniques: Positive Control
Journal: BMC Microbiology
Article Title: Zinc pyrithione impairs iron-sulfur cluster biogenesis in Mycobacterium tuberculosis
doi: 10.1186/s12866-025-04644-7
Figure Lengend Snippet: ZnPT induces impairment of Fe-S biogenesis and causes energy metabolism limitation
Article Snippet: Anti-Bacterial Compound Library (TargetMol, batch no. L4520),
Techniques: