Biometals最新文献

{"title":"Deciphering the role of human peroxiredoxins for combating lead and zinc mediated cellular toxicity using a yeast model.","authors":"Rahul Thakur, Reena V Saini, Sasanka Chakrabarti, Adesh K Saini","doi":"10.1007/s10534-026-00825-7","DOIUrl":"https://doi.org/10.1007/s10534-026-00825-7","url":null,"abstract":"<p><p>Elevated levels of heavy metals in cells lead to an imbalance of cellular redox homeostasis which is also seen in zinc and lead ion mediated toxicity. Human peroxiredoxins (hPrxI and hPrxII) are central regulators of redox balance; however, their role in mitigating heavy metal-induced stress remains unclear. Previously, we showed that the Saccharomyces cerevisiae model lacking TSA1 and TSA2 (tsa1tsa2Δ) showed growth defects in the presence of redox stressors that can be rescued by expressing hPrxI and hPrxII. In the present study, we utilized the tsa1tsa2Δ strain to understand the role of human homologs metal ion-induced stress. Growth assays demonstrated that ZnCl₂ and PbCl₂ markedly impaired the growth of tsa1tsa2Δ cells, whereas plasmid-based expression of hPrxI restored growth under both conditions. In contrast, hPrxII expression conferred protection only against ZnCl₂ toxicity. Measurements of intracellular reactive oxygen species (ROS) revealed significant accumulation upon ZnCl₂ and PbCl₂ exposure, which was alleviated by either hPrxI or hPrxII expression. Immunoblotting analyses indicated that hPrxI undergoes a monomer to dimer transition under heavy metal stress, suggesting redox-dependent structural modulation. Notably, catalytic mutants of both hPrxI and hPrxII partially restored growth and reduced ROS levels, demonstrating that their catalytic residues are not essential for conferring protection. These findings highlight isoforms specific and catalysis-independent roles of human peroxiredoxins in counteracting heavy metal-induced oxidative stress.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose and duration dependent effects of borax on ovarian structure and function in female rats.","authors":"Ozgur Bulmus, Cagla Celebi, Murat Celebi, Funda Gulcu Bulmus, Hasan Susar, Pakize Nur Akkaya, Fatma Bahar Sunay, Izzet Karahan","doi":"10.1007/s10534-026-00827-5","DOIUrl":"https://doi.org/10.1007/s10534-026-00827-5","url":null,"abstract":"<p><p>Boron is an essential trace element with emerging physiological significance; however, its effects on the female reproductive system remain poorly characterized. Most available studies are limited to single-dose applications or short-term exposures. In this study, we investigated the dose and duration dependent effects of oral boron exposure on ovarian follicular reserve, apoptosis, and reproductive hormone profiles in female Wistar albino rats. Animals were assigned to low- and high-dose borax groups (1250 and 5000 mg/kg/day, respectively) and exposed for short-term (7 and 15 days) or long-term (30 and 60 days) periods. At the end of each exposure period, ovarian tissues were collected for histomorphometric evaluation, while apoptosis was assessed using the TUNEL assay. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH) were also measured. Histomorphometric analysis revealed a significant reduction in primordial and primary follicle numbers, indicating depletion of the ovarian reserve, particularly in the high-dose and long-term exposure groups. TUNEL analysis demonstrated a marked increase in apoptotic cell density in ovarian tissues following prolonged boron administration. In parallel, boron exposure induced significant dose and duration dependent alterations in circulating reproductive hormone levels. Collectively, these findings suggest that chronic and high-dose oral boron exposure adversely affects ovarian morphology and function through enhanced apoptotic activity and disruption of endocrine homeostasis. These results highlight the potential reproductive toxicity of long-term boron exposure and underscore the need for further molecular studies to clarify the underlying mechanisms and to evaluate the translational relevance of these effects for human female reproductive health.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147831964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of zinc against testicular dysfunction, oxidative stress, and disturbances in biochemical, molecular, and tissue structure induced by hexavalent chromium.","authors":"Ali Y Naoom, Ali B Jebur, Raghda A El-Sayed, Mohamed M Abdel-Daim, Fatma M El-Demerdash","doi":"10.1007/s10534-026-00817-7","DOIUrl":"https://doi.org/10.1007/s10534-026-00817-7","url":null,"abstract":"<p><p>One well-known hazardous pollutant that damages testicles in both humans and animals is chromium hexavalent (CrVI). It has been established that zinc (Zn) is essential for spermatogenesis. Thus, the current work examines how Zn might shield rat testis from the detrimental effects of CrVI. Twenty-eight male rats were assigned to four groups the first was the control group; the second was given zinc sulfate (Zn; 1 mg/kg BW); the third received hexavalent chromium (CrVI; 2.5 mg/kg BW); and the fourth served as the protective group (Zn was given 60 min before CrVI). All treatments were given orally every day for four weeks. According to the results, rats intoxicated with CrVI exhibited a considerable decrease in body weight, enzymatic antioxidants, reduced glutathione, hydroxysteroid dehydrogenases (3β HSD, and 17β HSD), aminotransferases, and acid phosphatase activities, and a significant increase in the oxidative stress profile (TBARS, H₂O₂, PCC, XO, and NO). Testicular Bax, Cas-3, Bcl-2, Beclin-1, Nrf2, hormone levels, sperm quality, histopathological, and P53 immunohistochemical examinations were also shown to have significant changes compared to the control. Besides that, Zn pretreatment before CrVI intoxication improved the architecture of testicular tissue and P53 expression. Also, it significantly restored the majority of biochemical and molecular markers compared to the CrVI group. Additionally, oxidative stress indicators showed a notable change in response to individual Zn intake compared to the control. In conclusion, Zn significantly protects against CrVI-induced testicular failure, making it a unique strategy for processing heavy metal poisoning.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Siderophore-metal complexes in Paraburkholderia phymatum: structure elucidation of phymabactin.","authors":"Luca Bürgi, Daphné Golaz, Gabriella Pessi, Laurent Bigler","doi":"10.1007/s10534-026-00823-9","DOIUrl":"https://doi.org/10.1007/s10534-026-00823-9","url":null,"abstract":"<p><p>The symbiotic interaction between rhizobia and host plants takes place inside root nodules. Besides reducing atmospheric nitrogen into ammonium, which is then used by the plant to grow in nitrogen-deficient soils, certain rhizobia produce siderophores which enable iron uptake from the soil. Siderophores are strong iron chelators due to their hydroxamate, catecholate or carboxylate functional groups. In this work, the siderophores of the beta-rhizobial genus Paraburkholderia were analyzed by ultra-high-performance liquid chromatography (UHPLC) coupled to high-resolution mass spectrometry (HRMS). In particular, the production of the novel siderophore phymabactin by Paraburkholderia phymatum was confirmed and the structures of eleven derivatives were elucidated by tandem mass spectrometry (MS/MS) and nuclear magnetic resonance (NMR) spectroscopy. Phymabactins, consisting of a linear tetrapeptide backbone with hydroxamate and hydroxy-carboxylate groups, are structurally closely related to an already described family of siderophores called ornibactins. The acyl chain found in phymabactin derivatives is made up of eight, ten or twelve carbon atoms, contrarily to the more hydrophilic ornibactin derivatives with shorter acyl chains. Interestingly, spontaneous metal complexation of phymabactin derivatives with aluminum was observed. To explore this complexation in more detail, the collision cross sections (CCS) of phymabactins, ornibactins and corresponding metal complexes were determined by trapped ion mobility spectrometry. The CCS values of aluminum-phymabactin complexes were smaller than those of iron-phymabactin complexes, while an inverse relationship was observed for ornibactin complexes. In summary, this study discloses the molecular structures of phymabactins and investigates their metal complex formation.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platinum accumulation in chemotherapy: toxicity mechanisms, challenges, and mitigation strategies.","authors":"Yier Lai, Guodong Qiu, Zhiwei Zheng, Xiaoting Huang, Pi Guo, Yuling Zhang, Ling Fang","doi":"10.1007/s10534-026-00812-y","DOIUrl":"https://doi.org/10.1007/s10534-026-00812-y","url":null,"abstract":"<p><p>Platinum-based chemotherapeutic agents constitute the cornerstone of treatment for a wide range of solid tumors. However, residual platinum can persist in the body long after treatment cessation, leading to progressive accumulation, chronic multi-system toxicity, and significant impairment of patients' quality of life. The insidious onset and lack of specific monitoring methods often lead to the oversight of this treatment-related metal accumulation toxicity. This article reviews the environmental and occupational exposure risks of platinum, its unique pharmacokinetic properties, and elucidates how its irreversible binding to proteins and accumulation within mitochondria form the chemical basis for its long-term toxicity. It further elaborates on the core mechanisms underlying platinum accumulation-mediated multi-organ toxicity, including nephrotoxicity, neurotoxicity, and ototoxicity. The aim is to provide insights and directions for improving the long-term prognosis of cancer survivors by clarifying the toxicological mechanisms, clinical impacts, and future strategies for mitigating platinum-induced metal accumulation.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silicon mitigates aluminum toxicity in lettuce by improving photosynthetic pigments and antioxidant defense system.","authors":"Cheng Song, Zarina Bibi, Saqib Ali, Riaz Ahmad","doi":"10.1007/s10534-026-00819-5","DOIUrl":"https://doi.org/10.1007/s10534-026-00819-5","url":null,"abstract":"<p><p>Lettuce is economically an important leaf vegetable. Its production under acidic soils is low due to excessive aluminum (Al). Silicon (Si) supplementation is an effective approach to enhance stress tolerance in vegetables under acidic soil conditions. The present work aimed to explore the significance of Si application on lettuce plants under Al toxicity by modulation of morpho-physiological and biochemical indices. The current work comprises four treatments Al, Si, and a combination of Al + Si along with control. Al toxicity reduced lettuce growth and yield characteristics i.e., plant height, number of leaves, plant fresh biomass, plant dry biomass, rosette diameter, root fresh weight, root dry weight, SPAD index in comparison to normal plants (control). However, Si enhanced plant height, number of leaves, plant fresh biomass, plant dry biomass, rosette diameter, root fresh weight, root dry weight, SPAD index. The combination of Si + Al partially improved all the studied growth and yield traits. Al toxicity declines chlorophyll a, chlorophyll b, and carotenoids, while enhancing hydrogen peroxide (H₂O₂), malonaldehyde (MDA), superoxide dismutase (SOD), and catalase (CAT). Si improved chlorophyll a, chlorophyll b, carotenoids, SOD, and CAT, while Si declined H₂O₂ and MDA. The combination of Si + Al restored photosynthetic pigments and boosted the antioxidant defense system by decreasing oxidative stress markers. Al lessened photosynthesis, transpiration rate, and stomatal conductance, while Si enhanced these traits. Leaf gas exchange traits maintained under Si + Al. Hence, Si is considered a promising approach for the mitigation of Al toxicity in lettuce by modulation of morpho-physiological and biochemical insights, focusing on sustainable production.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759111","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioaccumulation and nutritional impact of fluoride in Pleurotus ostreatus and Pleurotus djamor with human health risk assessment.","authors":"Ayan De, Jit Sarkar, Diptosh Das, Deepanjan Mridha, Moitri Let, Bhuban Gangopadhyay, Kunal Sarkar, Madhusudan Das, Tarit Roychowdhury, Krishnendu Archarya, Rajib Bandopadhyay, Anindya Sundar Panja","doi":"10.1007/s10534-026-00820-y","DOIUrl":"https://doi.org/10.1007/s10534-026-00820-y","url":null,"abstract":"<p><p>Pleurotus species are nutritionally rich fungi, yet their potential to bioaccumulate environmental fluoride (F⁻) necessitates careful scientific evaluation further. In this study, Pleurotus mushrooms cultivated on F⁻ enriched substrates exhibited significant bioaccumulation of F⁻, indicating their sensitivity to substrate quality and environmental contamination. Supplementation with calcium (Ca) played a crucial physiological role by reducing F⁻ toxicity within the fruiting bodies of mushroom, although its effects were species dependent. Notably, Ca addition mitigated F⁻ stress at the biochemical and cellular level in Pleurotus ostreatus, whereas P. djamor experienced a reduction in growth performance, demonstrating differential tolerance mechanisms. Molecular-level assessment through FTIR-spectroscopy highlighted marked alterations in functional groups associated with proteins, lipids, and carbohydrates under combined F⁻ and Ca exposure, emphasizing stress-induced metabolic shifts. Field-based evaluations further validated laboratory observations, revealing substantial F⁻ accumulation in mushrooms grown using fluoridated-straw and F⁻ rich groundwater, particularly in Set 1N (96.6 mg/kg-dw) and Set 4N (46 mg/kg-dw). Subcellular fractionation studies confirmed that accumulated fluoride predominantly localized within the cell wall fraction, suggesting a sequestration strategy for detoxification. Bioconcentration factor (BCF) analysis indicated higher accumulation in P. ostreatus relative to P. djamor. However, despite partial mitigation by Ca supplementation and health risk assessments demonstrated that both mushroom species exceeded the non-carcinogenic risk threshold for children when cultivated in traditional way under contaminated conditions. These findings underscore the importance of using controlled, F⁻ free substrates and clean irrigation sources to ensure food safety and promote sustainable mushroom cultivation practices, particularly in fluoride-affected regions such as West Bengal, India.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salidroside in heavy metal toxicity: a mechanistic review of antioxidant, anti-inflammatory, and anti-apoptotic pathways.","authors":"Wenjie Sun, Chenxu Hu, Zhao Xiao, Zehua Tao, Chongyang Guo, Yubin Zhang, Soha M Atya, Anatoly V Skalny, Michael Aschner, Bobo Yang, Hongbin Zhou, Alexey A Tinkov, Rongzhu Lu","doi":"10.1007/s10534-026-00815-9","DOIUrl":"https://doi.org/10.1007/s10534-026-00815-9","url":null,"abstract":"<p><p>Environmental exposure to heavy metals poses significant threats to human health. In view of side effects and limitations of present chelation therapy, further search for the potential agents counteracting metal toxicity is warranted. Salidroside, the main active ingredient of Rhodiola rosea, has shown potential as a natural agent for alleviating heavy metal toxicity. Our aim is to review the mechanisms by which salidroside mitigates toxicity induced by various heavy metals, providing a basis for developing protective strategies and offering a new perspective for future research. Research has shown that salidroside exerts protections against metal-induced toxicity through multiple mechanisms, including: (1) Regulating the HIF-1α/mTOR pathway to alleviate hypoxic injury; (2) Activating Nrf2/ARE antioxidant pathway; (3) Inhibiting mitochondrial pathway of apoptosis (Bcl-2/Bax/caspase-3); (4) Enhancing gap junctional intercellular communication (GJIC);(5) Down-regulating pro-inflammatory signaling through targeting MAPK and NF-κB pathways.Modulation of these signaling pathways, as well as certain other mechanisms, are involved in the protective effects of salidroside against metal toxicity in liver, brain, heart, kidneys and other organs, as evidenced from in vivo and in vitro studies. Compared with traditional chelating agents, salidroside has low toxicity and promising efficacy in alleviating cobalt, cadmium, lead, manganese, methylmercury, cisplatin, arsenic and iron toxicity. Therefore, salidroside holds promise as a new natural product for mitigating metal-induced toxicity and further studies are needed to clarify its clinical applicability.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effect of magnesium on indomethacin-induced gastric ulcer in mice.","authors":"Roya Rostami, Akram Eidi, Pejman Mortazavi, Shahrebano Oryan","doi":"10.1007/s10534-026-00803-z","DOIUrl":"https://doi.org/10.1007/s10534-026-00803-z","url":null,"abstract":"<p><p>Gastric ulcer disease is a common problem of the gastrointestinal tract, with increasing incidence and prevalence attributed to a loss of balance between aggressive and protective factors. Gastric ulcer is a chronic condition characterized by damage to the mucosal, submucosal, and muscular layers of the stomach, primarily caused by excessive secretion of gastric acid, pepsin, and other digestive enzymes. The role of antioxidants in promoting ulcer healing is well established. Magnesium (Mg), being a main macro element, exhibits various beneficial effects, including antioxidant, analgesic, anti-inflammatory, antidiabetic, antacid, anti-apoptotic, and free radical-scavenging properties. In this study, we investigated the effect of magnesium sulfate (MgSO₄) on indomethacin-induced gastric ulcers in male Balb/c mice. The effect of orally administered MgSO₄ (0.05, 0.1, and 0.2 g/kg) was assessed in both gastric ulcer and healthy mice. The animals were randomly assigned to 10 groups: healthy control; sham; MgSO₄ alone at 0.05, 0.1, or 0.2 g/kg; gastric ulcer control (indomethacin, 18 mg/kg); MgSO₄ at 0.05, 0.1, or 0.2 g/kg) plus indomethacin; and omeprazole (20 mg/kg) plus indomethacin. Treatment were administered intragastrically for 14 consecutive days. All mice underwent a 24-h fasting period before the final day of treatment. Six hours after the last dose, indomethacin was administered orally to induce gastric ulceration. The mice were then sacrificed for histopathological and biochemical assessments. Administration of MgSO₄ significantly reduced the ulcerated area, decreased malondialdehyde (MDA) levels, and increased gastric antioxidative enzyme activity, consistent with histopathological evidence of mucosal protection. In ulcer-induced mice, MgSO₄ significantly decreased the expression of Epidermal Growth Factor (EGF), 70-kDa Heat Shock Protein (HSP-70), and Spasmolytic Polypeptide (SP) expression in the gastric tissue. In conclusion, magnesium may act as an anti-ulcerogenic and gastroprotective agent in mice.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147727975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Meta-analysis reveals a core iron-responsive gene signature in Mycobacterium tuberculosis linking siderophore biosynthesis, virulence, and metabolic adaptation.","authors":"Gauri Shankar, Yusuf Akhter","doi":"10.1007/s10534-026-00818-6","DOIUrl":"https://doi.org/10.1007/s10534-026-00818-6","url":null,"abstract":"<p><p>The meta-analysis integrates transcriptomic data from two independent datasets (GSE8732 and GSE84554) to elucidate Mycobacterium tuberculosis (Mtb)'s transcriptional response to iron limitation, a key host defense mechanism. The study identifies a core set of consistently differentially expressed genes (DEGs) critical for Mtb's survival under iron-restricted conditions. Key upregulated genes include those involved in siderophore biosynthesis (mbtA, mbtB, mbtE, mbtI), which are essential for iron acquisition, and components of the ESX secretion system (esxG, esxH, esxR, esxS), linking iron scavenging to virulence. Additionally, PE/PPE family genes (PPE37, PE5), implicated in immune evasion, were consistently upregulated, suggesting their role in host-pathogen interactions during iron scarcity. Conversely, downregulated genes included iron storage proteins (bfrA), regulatory factors (ideR, sigB, rpoC), and metabolic enzymes (aspC, frdA), reflecting a strategic shift away from iron-dependent processes to conserve resources. Temporal analysis revealed a dynamic adaptation process: early-phase responses prioritized iron acquisition, while prolonged starvation induced metabolic restructuring (e.g., upregulation of fadD33, kasB) and stress responses (grpE). The iron-dependent regulator IdeR emerged as a central player, derepressing iron acquisition genes under low iron but also revealing additional regulatory layers. The consistent DEGs across datasets validate their biological significance and highlight potential therapeutic targets, such as siderophore biosynthesis and ESX systems, to disrupt Mtb's adaptation during infection. This study advances insights into Mtb's pathogenicity and survival strategies under host-imposed iron restriction, offering a framework for novel anti-tuberculosis interventions.</p>","PeriodicalId":491,"journal":{"name":"Biometals","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147715477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}