Marisa S Egan, Raquel de Macedo, Joseph P Zackular
Trace metals are indispensable nutritional factors for all living organisms. During host-pathogen interactions, they serve as crucial resources that dictate infection outcomes. Accordingly, the host uses a defense strategy known as nutritional immunity, which relies on coordinated metal chelation to mitigate bacterial advances. In response, pathogens employ complex strategies to secure these resources at sites of infection. In the gastrointestinal (GI) tract, the microbiota must also acquire metals for survival, making metals a central line of competition in this complex ecosystem. In this minireview, we outline how bacteria secure iron, zinc, and manganese from the host with a focus on the GI tract. We also reflect on how host dietary changes impact disease outcomes and discuss therapeutic opportunities to target bacterial metal uptake systems. Ultimately, we find that recent discoveries on the dynamics of transition metals at the host-pathogen-microbiota interface have reshaped our understanding of enteric infections and provide insights into virulence strategies, microbial cooperation, and antibacterial strategies.
{"title":"UMetals in the Gut: Microbial Strategies to Overcome Nutritional Immunity in the Intestinal Tract.","authors":"Marisa S Egan, Raquel de Macedo, Joseph P Zackular","doi":"10.1093/mtomcs/mfae052","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae052","url":null,"abstract":"<p><p>Trace metals are indispensable nutritional factors for all living organisms. During host-pathogen interactions, they serve as crucial resources that dictate infection outcomes. Accordingly, the host uses a defense strategy known as nutritional immunity, which relies on coordinated metal chelation to mitigate bacterial advances. In response, pathogens employ complex strategies to secure these resources at sites of infection. In the gastrointestinal (GI) tract, the microbiota must also acquire metals for survival, making metals a central line of competition in this complex ecosystem. In this minireview, we outline how bacteria secure iron, zinc, and manganese from the host with a focus on the GI tract. We also reflect on how host dietary changes impact disease outcomes and discuss therapeutic opportunities to target bacterial metal uptake systems. Ultimately, we find that recent discoveries on the dynamics of transition metals at the host-pathogen-microbiota interface have reshaped our understanding of enteric infections and provide insights into virulence strategies, microbial cooperation, and antibacterial strategies.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692250","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}
Diana Galea, Martin Herzberg, Dirk Dobritzsch, Matt Fuszard, Dietrich H Nies
Cupriavidus metallidurans CH34 is a metal-resistant bacterium. Its metal homeostasis is based on a flow equilibrium of metal ion uptake and efflux reactions, which adapts to changing metal concentrations within an hour. At high metal concentrations, up-regulation of the genes for metal efflux systems occurs within minutes. Here, we investigates the changes in the bacterial proteome accompanying these genetic and physiological events after 1.5 cell duplications, which took 3 hours. To that end, C. metallidurans CH34 and its plasmid-free derivative, AE104, were challenged either with a toxic metal mix or were cultivated under metal-starvation conditions, followed by bottom-up proteomics. When metal-shocked or -starved cells were compared with their respective controls, 3 540 proteins changed in abundance, with 76% appearing in one, but not the other, condition; the remaining 24% were up- or down-regulated. Metal-shocked C. metallidurans strains had adjusted their proteomes to combat metal stress. The most prominent polypeptides were the products of the plasmid-encoded metal-resistance determinants in strain CH34, particularly the CzcCBA transenvelope efflux system. Moreover, the influence of antisense transcripts on the proteome was also revealed. In one specific example, the impact of an asRNA on the abundance of gene products could be demonstrated and this yielded new insights into the function of the transmembrane efflux complex ZniCBA under conditions of metal starvation.
{"title":"Linking the transcriptome to physiology: response of the proteome of cupriavidus metallidurans to changing metal availability.","authors":"Diana Galea, Martin Herzberg, Dirk Dobritzsch, Matt Fuszard, Dietrich H Nies","doi":"10.1093/mtomcs/mfae058","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae058","url":null,"abstract":"<p><p>Cupriavidus metallidurans CH34 is a metal-resistant bacterium. Its metal homeostasis is based on a flow equilibrium of metal ion uptake and efflux reactions, which adapts to changing metal concentrations within an hour. At high metal concentrations, up-regulation of the genes for metal efflux systems occurs within minutes. Here, we investigates the changes in the bacterial proteome accompanying these genetic and physiological events after 1.5 cell duplications, which took 3 hours. To that end, C. metallidurans CH34 and its plasmid-free derivative, AE104, were challenged either with a toxic metal mix or were cultivated under metal-starvation conditions, followed by bottom-up proteomics. When metal-shocked or -starved cells were compared with their respective controls, 3 540 proteins changed in abundance, with 76% appearing in one, but not the other, condition; the remaining 24% were up- or down-regulated. Metal-shocked C. metallidurans strains had adjusted their proteomes to combat metal stress. The most prominent polypeptides were the products of the plasmid-encoded metal-resistance determinants in strain CH34, particularly the CzcCBA transenvelope efflux system. Moreover, the influence of antisense transcripts on the proteome was also revealed. In one specific example, the impact of an asRNA on the abundance of gene products could be demonstrated and this yielded new insights into the function of the transmembrane efflux complex ZniCBA under conditions of metal starvation.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674430","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}
Cornelia Große, Jan Grau, Martin Herzberg, Dietrich H Nies
Cupriavidus metallidurans is able to thrive in metal-rich environments but also survives metal starvation. Expression of metal resistance determinants in C. metallidurans was investigated on a global scale. C. metallidurans was challenged with a MultiTox metal mix specifically designed for the wildtype strain CH34 and its plasmid-free derivative AE104, including treatment with ethylenediamintetraacetate (EDTA), or without challenge. The sense and antisense transcripts were analyzed in both strains and under all three conditions by RNASeq. A total of 10 757 antisense transcripts (ASTs) were assigned to sense signals from genes and untranslated regions, and 1 319 of these ASTs were expressed and were longer than 50 bases. Most of these (82%) were dual-use transcripts that contained antisense and sense regions, but ASTs (16%) were also observed that had no sense regions. Especially in metal-treated cells of strains CH34 and AE104, up- or down-regulated sense transcripts were accompanied by antisense transcription activities that were also regulated. The presence of selected asRNAs was verified by RT-PCR. Following metal stress, expression of genes encoding components of the respiratory chain, motility, transcription, translation and protein export were down-regulated. This should also affect the integration of the metal efflux pumps into the membrane and the supply of the energy required to operate them. To solve this dilemma, transcripts for the metal efflux pumps may be stabilized by interactions with ASTs to allow their translation and import into the membrane. Alternatively, metal stress possibly causes recruitment of RNA polymerase from housekeeping genes for preferential expression of metal resistance determinants.
{"title":"Antisense transcription is associated with expression of metal resistance determinants in Cupriavidus metallidurans CH34.","authors":"Cornelia Große, Jan Grau, Martin Herzberg, Dietrich H Nies","doi":"10.1093/mtomcs/mfae057","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae057","url":null,"abstract":"<p><p>Cupriavidus metallidurans is able to thrive in metal-rich environments but also survives metal starvation. Expression of metal resistance determinants in C. metallidurans was investigated on a global scale. C. metallidurans was challenged with a MultiTox metal mix specifically designed for the wildtype strain CH34 and its plasmid-free derivative AE104, including treatment with ethylenediamintetraacetate (EDTA), or without challenge. The sense and antisense transcripts were analyzed in both strains and under all three conditions by RNASeq. A total of 10 757 antisense transcripts (ASTs) were assigned to sense signals from genes and untranslated regions, and 1 319 of these ASTs were expressed and were longer than 50 bases. Most of these (82%) were dual-use transcripts that contained antisense and sense regions, but ASTs (16%) were also observed that had no sense regions. Especially in metal-treated cells of strains CH34 and AE104, up- or down-regulated sense transcripts were accompanied by antisense transcription activities that were also regulated. The presence of selected asRNAs was verified by RT-PCR. Following metal stress, expression of genes encoding components of the respiratory chain, motility, transcription, translation and protein export were down-regulated. This should also affect the integration of the metal efflux pumps into the membrane and the supply of the energy required to operate them. To solve this dilemma, transcripts for the metal efflux pumps may be stabilized by interactions with ASTs to allow their translation and import into the membrane. Alternatively, metal stress possibly causes recruitment of RNA polymerase from housekeeping genes for preferential expression of metal resistance determinants.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674424","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}
Kidney stones, as typical biominerals produced within the human body, pose a significant threat to human health, affecting over 12% of the global population. However, the exact mechanisms underlying their formation are not fully understood. Recent metal isotopic analysis provides a new way to study the roles of metal cations in biological processes within organisms. Here we report the Mg isotope ratios of human kidney stones for the first time. The total range of measured values for δ26Mg in kidney stones is 1.05‰, from-1.12‰ to-0.07‰. Our data exhibit a significant 24Mg enrichment compared with the values calculated from density functional theory. We suggest that the Mg-isotopic fractionations in vivo are linked to active Mg transport mediated by proteins during intestinal absorption and preferential renal reabsorption of ionized Mg2+ via tight junctional proteins. Our results indicate that the inhibitory effect of Mg on kidney stones is related to the kink-blocking mechanism, and the incorporation of hydrated Mg lessens the extent of inhibition and the magnitude of isotope discrimination. We show that metal isotopes provide new insights into the underlying the biological processes and human health.
{"title":"Natural variation of magnesium stable isotopes in human kidney stones.","authors":"Jinke Liu, Guilin Han, Yu Tian, Rui Qu, Di Wang, Yanan Shen","doi":"10.1093/mtomcs/mfae056","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae056","url":null,"abstract":"<p><p>Kidney stones, as typical biominerals produced within the human body, pose a significant threat to human health, affecting over 12% of the global population. However, the exact mechanisms underlying their formation are not fully understood. Recent metal isotopic analysis provides a new way to study the roles of metal cations in biological processes within organisms. Here we report the Mg isotope ratios of human kidney stones for the first time. The total range of measured values for δ26Mg in kidney stones is 1.05‰, from-1.12‰ to-0.07‰. Our data exhibit a significant 24Mg enrichment compared with the values calculated from density functional theory. We suggest that the Mg-isotopic fractionations in vivo are linked to active Mg transport mediated by proteins during intestinal absorption and preferential renal reabsorption of ionized Mg2+ via tight junctional proteins. Our results indicate that the inhibitory effect of Mg on kidney stones is related to the kink-blocking mechanism, and the incorporation of hydrated Mg lessens the extent of inhibition and the magnitude of isotope discrimination. We show that metal isotopes provide new insights into the underlying the biological processes and human health.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674433","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}
The shell color of Corbicula clams, which are globally distributed, is roughly divided into yellowish and blackish depending on the environmental conditions of the sediment. The formation of an iron-L-3,4-dihydroxyphenylalanine (DOPA) complex in a thin organic layer, called the periostracum, on a calcareous layer causes the blackening of the clamshell. However, the iron-DOPA complex formation mechanism is unclear. To reveal how the iron is transported from the aquatic environment to the periostracum, cross-sectional analyses of the shell were conducted using an electron probe microanalyzer (EPMA) and Raman spectroscopy to investigate the distribution and structure of iron in the shell. Iron was only present in the periostracum, excluding deposition, and all iron was in the form of an iron-DOPA complex. Attenuated total reflection infrared spectroscopy and oxygen K-edge X-ray absorption fine structure spectroscopy revealed that the molecular structure of the native periostracum is independent of shell color. These results indicate that dissolved iron-organic complexes diffuse from the aqueous environment to the periostracum, forming iron-DOPA complex through ligand exchange. Because the iron-DOPA complex color depends on the pH, the shell color can serve as a historical indicator of the shell's growth environment.
蚬壳分布于全球各地,根据沉积物的环境条件,其外壳颜色大致分为淡黄色和黑色。铁-L-3,4-二羟基苯丙氨酸(DOPA)复合物在钙质层上的薄有机层(称为围岩)中形成,导致蛤壳变黑。然而,铁-DOPA 复合物的形成机制尚不清楚。为了揭示铁是如何从水生环境迁移到蚬壳的,研究人员使用电子探针显微分析仪(EPMA)和拉曼光谱对蚬壳进行了横截面分析,以研究铁在蚬壳中的分布和结构。除沉积物外,铁只存在于外壳中,而且所有的铁都以铁-DOPA 复合物的形式存在。衰减全反射红外光谱和氧 K 边 X 射线吸收精细结构光谱显示,原生围岩的分子结构与外壳颜色无关。这些结果表明,溶解的铁-有机络合物从水环境扩散到围岩,通过配体交换形成铁-DOPA络合物。由于铁-DOPA 复合物的颜色取决于 pH 值,因此贝壳的颜色可以作为贝壳生长环境的历史指标。
{"title":"Formation mechanism of iron-catechol complexes in the colored periostracum of Corbicula spp.","authors":"Kuniko Takemoto, Masataka Murakami, Yoshihiro Ueno, Daiya Bamba, Hirona Yamagishi","doi":"10.1093/mtomcs/mfae055","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae055","url":null,"abstract":"<p><p>The shell color of Corbicula clams, which are globally distributed, is roughly divided into yellowish and blackish depending on the environmental conditions of the sediment. The formation of an iron-L-3,4-dihydroxyphenylalanine (DOPA) complex in a thin organic layer, called the periostracum, on a calcareous layer causes the blackening of the clamshell. However, the iron-DOPA complex formation mechanism is unclear. To reveal how the iron is transported from the aquatic environment to the periostracum, cross-sectional analyses of the shell were conducted using an electron probe microanalyzer (EPMA) and Raman spectroscopy to investigate the distribution and structure of iron in the shell. Iron was only present in the periostracum, excluding deposition, and all iron was in the form of an iron-DOPA complex. Attenuated total reflection infrared spectroscopy and oxygen K-edge X-ray absorption fine structure spectroscopy revealed that the molecular structure of the native periostracum is independent of shell color. These results indicate that dissolved iron-organic complexes diffuse from the aqueous environment to the periostracum, forming iron-DOPA complex through ligand exchange. Because the iron-DOPA complex color depends on the pH, the shell color can serve as a historical indicator of the shell's growth environment.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674426","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}
M Jake Pushie, Nicole J Sylvain, Huishu Hou, Nicole Pendleton, Richard Wang, Liam Zimmermann, Maxwell Pally, Francisco S Cayabyab, Lissa Peeling, Michael E Kelly
The brain is a privileged organ with regards to its trace element composition and maintains a robust barrier system to sequester this specialized environment from the rest of the body and the vascular system. Stroke is caused by loss of adequate blood flow to a region of the brain. Without adequate blood flow ischemic changes begin almost immediately, triggering an ischemic cascade, characterized by ion dysregulation, loss of function, oxidative damage, cellular degradation, and break down of the barrier that helps maintain this environment. Ion dysregulation is a hallmark of stroke pathophysiology and we observe that most elements in the brain are dysregulated after stroke. X-ray fluorescence-based detection of physiological changes in the neurometallome after stroke reveals profound ion dysregulation within the lesion and surrounding tissue. Not only are most elements significantly dysregulated after stroke, but the level of dysregulation cannot be predicted from a cell-level description of dysregulation. X-ray fluorescence imaging reveals that the stroke lesion retains < 25% of essential K+ after stroke, but this element is not concomitantly elevated elsewhere in the organ. Moreover, elements like Na+, Ca2+, and Cl- are vastly elevated above levels available in normal brain tissue (>400%, >200%, and > 150%, respectively). We hypothesize that weakening of the blood-brain-barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). The changes observed for the neurometallome likely has consequences for the potential to rescue infarcted tissue, but also presents specific targets for treatment.
大脑在微量元素组成方面是一个特殊的器官,并保持着一个强大的屏障系统,将这一特殊环境与身体其他部位和血管系统隔绝开来。脑卒中是由于大脑某一区域失去充足的血流而引起的。如果没有足够的血流,缺血性变化几乎立即开始,引发缺血级联反应,其特点是离子失调、功能丧失、氧化损伤、细胞退化以及有助于维持这种环境的屏障被破坏。离子失调是中风病理生理学的一个标志,我们观察到中风后大脑中的大多数元素都失调了。基于 X 射线荧光技术对中风后神经金属组生理变化的检测显示,病变部位和周围组织内的离子严重失调。不仅大多数元素在中风后明显失调,而且失调的程度无法从细胞水平的失调描述中预测。X 射线荧光成像显示,中风病灶的保留率分别为 400%、>200% 和 >150%)。我们推测,中风后血脑屏障的减弱允许元素顺着浓度梯度自由扩散,从而使中风病灶与血液(以及含有脑间质和脑脊液的区室)处于平衡状态。观察到的神经金属组的变化可能会对挽救梗死组织的潜力产生影响,同时也为治疗提供了特定的目标。
{"title":"X-ray fluorescence mapping of brain tissue reveals the profound extent of trace element dysregulation in stroke pathophysiology.","authors":"M Jake Pushie, Nicole J Sylvain, Huishu Hou, Nicole Pendleton, Richard Wang, Liam Zimmermann, Maxwell Pally, Francisco S Cayabyab, Lissa Peeling, Michael E Kelly","doi":"10.1093/mtomcs/mfae054","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae054","url":null,"abstract":"<p><p>The brain is a privileged organ with regards to its trace element composition and maintains a robust barrier system to sequester this specialized environment from the rest of the body and the vascular system. Stroke is caused by loss of adequate blood flow to a region of the brain. Without adequate blood flow ischemic changes begin almost immediately, triggering an ischemic cascade, characterized by ion dysregulation, loss of function, oxidative damage, cellular degradation, and break down of the barrier that helps maintain this environment. Ion dysregulation is a hallmark of stroke pathophysiology and we observe that most elements in the brain are dysregulated after stroke. X-ray fluorescence-based detection of physiological changes in the neurometallome after stroke reveals profound ion dysregulation within the lesion and surrounding tissue. Not only are most elements significantly dysregulated after stroke, but the level of dysregulation cannot be predicted from a cell-level description of dysregulation. X-ray fluorescence imaging reveals that the stroke lesion retains < 25% of essential K+ after stroke, but this element is not concomitantly elevated elsewhere in the organ. Moreover, elements like Na+, Ca2+, and Cl- are vastly elevated above levels available in normal brain tissue (>400%, >200%, and > 150%, respectively). We hypothesize that weakening of the blood-brain-barrier after stroke allows elements to freely diffuse down their concentration gradient so that the stroke lesion is in equilibrium with blood (and the compartments containing brain interstitial fluid and cerebrospinal fluid). The changes observed for the neurometallome likely has consequences for the potential to rescue infarcted tissue, but also presents specific targets for treatment.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637943","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}
Seyed Mostafa Hosseinpour Mashkani, David Bishop, Mika T Westerhausen, Paul A Adlard, S Mojtaba Golzan
Transition metals like copper, iron, and zinc are vital for normal central nervous system function and are also linked to neurodegeneration, particularly in the onset and progression of Alzheimer's disease (AD). Their alterations in AD, identified prior to amyloid plaque aggregation, offer a unique target for staging pre-amyloid AD. However, analysing their levels in the brain is extremely challenging, necessitating the development of alternative approaches. Here, we utilised laser ablation-inductively coupled plasma-mass spectrometry and solution nebulisation-inductively coupled plasma-mass spectrometry to quantitatively measure Cu, Fe, and Zn concentrations in the retina and hippocampus samples obtained from human donors (i.e., AD and healthy controls), and in the APP/PS1 mouse model of AD, and Wild Type controls, aged 9 and 18 months. Our findings revealed significantly elevated Cu, Fe, and Zn levels in the retina (*p < 0.05, **p < 0.01, ***p < 0.001) and hippocampus (*p < 0.05, *p < 0.05, *p < 0.05) of human AD samples compared to healthy controls. Conversely, APP/PS1 mouse models exhibited notably lower metal levels in the same regions compared to WT mice, Cu, Fe, and Zn levels in the retina (**p < 0.01, *p < 0.05, *p < 0.05) and hippocampus (**p < 0.01, **p < 0.01, *p < 0.05). The contrasting metal profiles in human and mouse samples, yet similar patterns within each species' retina and brain, suggest the retina mirrors cerebral metal dyshomeostasis in AD. Our findings lay the groundwork for staging pre-AD pathophysiology through assessment of transition metal levels in the retina.
{"title":"Alterations in Zinc, Copper, and Iron Levels in the Retina and Brain of Alzheimer's Disease Patients and the APP/PS1 Mouse Model.","authors":"Seyed Mostafa Hosseinpour Mashkani, David Bishop, Mika T Westerhausen, Paul A Adlard, S Mojtaba Golzan","doi":"10.1093/mtomcs/mfae053","DOIUrl":"https://doi.org/10.1093/mtomcs/mfae053","url":null,"abstract":"<p><p>Transition metals like copper, iron, and zinc are vital for normal central nervous system function and are also linked to neurodegeneration, particularly in the onset and progression of Alzheimer's disease (AD). Their alterations in AD, identified prior to amyloid plaque aggregation, offer a unique target for staging pre-amyloid AD. However, analysing their levels in the brain is extremely challenging, necessitating the development of alternative approaches. Here, we utilised laser ablation-inductively coupled plasma-mass spectrometry and solution nebulisation-inductively coupled plasma-mass spectrometry to quantitatively measure Cu, Fe, and Zn concentrations in the retina and hippocampus samples obtained from human donors (i.e., AD and healthy controls), and in the APP/PS1 mouse model of AD, and Wild Type controls, aged 9 and 18 months. Our findings revealed significantly elevated Cu, Fe, and Zn levels in the retina (*p < 0.05, **p < 0.01, ***p < 0.001) and hippocampus (*p < 0.05, *p < 0.05, *p < 0.05) of human AD samples compared to healthy controls. Conversely, APP/PS1 mouse models exhibited notably lower metal levels in the same regions compared to WT mice, Cu, Fe, and Zn levels in the retina (**p < 0.01, *p < 0.05, *p < 0.05) and hippocampus (**p < 0.01, **p < 0.01, *p < 0.05). The contrasting metal profiles in human and mouse samples, yet similar patterns within each species' retina and brain, suggest the retina mirrors cerebral metal dyshomeostasis in AD. Our findings lay the groundwork for staging pre-AD pathophysiology through assessment of transition metal levels in the retina.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612942","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}
François L H Tissot, Dylan Cleveland, Rosa Grigoryan, Michael A Kipp, Roxana T Shafiee, Emily Miaou, Rithika Chunduri, Hayward Melton, Theo Tacail, Dan Razionale
Calcium (Ca) isotopes in blood/urine are emerging biomarkers of bone mineral balance (BMB) in the human body. While multiple studies have investigated Ca isotopes in patients suffering from diseases affecting BMB, comparatively little effort has been devoted to understanding the homeostasis of Ca isotopes in healthy individuals. Here, we report on a longitudinal study of the urine Ca isotope composition (δ44/42CaUrine) from 22 healthy participants (age 19-60) over timescales ranging from days to months. Data from a single participant collected over a 30-day period show that morning urine is an excellent proxy for 24-h pooled urine fractions. Data from all participants reveal large inter-individual variability in δ44/42CaUrine (up to 2.2‰), which is partly due to anthropometric differences, as shown by a correlation between the participants' body mass index (BMI) and δ44/42CaUrine values. In contrast, intra-individual data reveal encouraging stability (within ∼±0.2-0.3‰) over timescales >160 days, indicating that self-referencing approaches for BMB monitoring hold greater promise than cross-sectional ones. Our data confirm that intra-individual δ44/42CaUrine variations are mainly a function of Ca reabsorption in the kidney, but also reveal the impact of other (and at times equally important) drivers, such as diet, alcohol consumption, physical exercise, or fasting. We also find that a magnetic resonance imaging contrast agent (gadolinium) can lead to artifacts during Ca isotope analysis. Based on our results, a series of practical considerations for the use of Ca isotopes in urine as tracers of BMB are presented.
{"title":"Magnitude and timescales of Ca isotope variability in human urine: implications for bone mass balance monitoring.","authors":"François L H Tissot, Dylan Cleveland, Rosa Grigoryan, Michael A Kipp, Roxana T Shafiee, Emily Miaou, Rithika Chunduri, Hayward Melton, Theo Tacail, Dan Razionale","doi":"10.1093/mtomcs/mfae050","DOIUrl":"10.1093/mtomcs/mfae050","url":null,"abstract":"<p><p>Calcium (Ca) isotopes in blood/urine are emerging biomarkers of bone mineral balance (BMB) in the human body. While multiple studies have investigated Ca isotopes in patients suffering from diseases affecting BMB, comparatively little effort has been devoted to understanding the homeostasis of Ca isotopes in healthy individuals. Here, we report on a longitudinal study of the urine Ca isotope composition (δ44/42CaUrine) from 22 healthy participants (age 19-60) over timescales ranging from days to months. Data from a single participant collected over a 30-day period show that morning urine is an excellent proxy for 24-h pooled urine fractions. Data from all participants reveal large inter-individual variability in δ44/42CaUrine (up to 2.2‰), which is partly due to anthropometric differences, as shown by a correlation between the participants' body mass index (BMI) and δ44/42CaUrine values. In contrast, intra-individual data reveal encouraging stability (within ∼±0.2-0.3‰) over timescales >160 days, indicating that self-referencing approaches for BMB monitoring hold greater promise than cross-sectional ones. Our data confirm that intra-individual δ44/42CaUrine variations are mainly a function of Ca reabsorption in the kidney, but also reveal the impact of other (and at times equally important) drivers, such as diet, alcohol consumption, physical exercise, or fasting. We also find that a magnetic resonance imaging contrast agent (gadolinium) can lead to artifacts during Ca isotope analysis. Based on our results, a series of practical considerations for the use of Ca isotopes in urine as tracers of BMB are presented.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589615","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}
Nudzejma Stulanovic, Yasmine Kerdel, Loïc Belde, Lucas Rezende, Benoit Deflandre, Pierre Burguet, Romane Denoel, Déborah Tellatin, Augustin Rigolet, Marc Hanikenne, Loïc Quinton, Marc Ongena, Sébastien Rigali
Streptomyces scabiei is the causative agent of common scab on root and tuber crops. Life in the soil imposes intense competition between soil-dwelling microorganisms, and we evaluated here the antimicrobial properties of S. scabiei. Under laboratory culture conditions, increasing peptone levels correlated with increased growth inhibitory properties of S. scabiei. Comparative metabolomics showed that production of S. scabiei siderophores (desferrioxamines, pyochelin, scabichelin, and turgichelin) increased with the quantity of peptone, thereby suggesting that they participate in growth inhibition. Mass spectrometry imaging further confirmed that the zones of secreted siderophores and growth inhibition coincided. Moreover, either the repression of siderophore production or the neutralization of their iron-chelating activity led to increased microbial growth. Replacement of peptone by natural nitrogen sources regularly used as fertilizers such as ammonium nitrate, ammonium sulfate, sodium nitrate, and urea also triggered siderophore production in S. scabiei. The observed effect is not mediated by alkalinization of the medium as increasing the pH without providing additional nitrogen sources did not induce siderophore production. The nitrogen-induced siderophore production also inhibited the growth of important plant pathogens. Overall, our work suggests that not only the iron availability but also the nitrogen fertilizer sources could significantly impact the competition for iron between crop-colonizing microorganisms.
{"title":"Nitrogen fertilizers activate siderophore production by the common scab causative agent Streptomyces scabiei.","authors":"Nudzejma Stulanovic, Yasmine Kerdel, Loïc Belde, Lucas Rezende, Benoit Deflandre, Pierre Burguet, Romane Denoel, Déborah Tellatin, Augustin Rigolet, Marc Hanikenne, Loïc Quinton, Marc Ongena, Sébastien Rigali","doi":"10.1093/mtomcs/mfae048","DOIUrl":"10.1093/mtomcs/mfae048","url":null,"abstract":"<p><p>Streptomyces scabiei is the causative agent of common scab on root and tuber crops. Life in the soil imposes intense competition between soil-dwelling microorganisms, and we evaluated here the antimicrobial properties of S. scabiei. Under laboratory culture conditions, increasing peptone levels correlated with increased growth inhibitory properties of S. scabiei. Comparative metabolomics showed that production of S. scabiei siderophores (desferrioxamines, pyochelin, scabichelin, and turgichelin) increased with the quantity of peptone, thereby suggesting that they participate in growth inhibition. Mass spectrometry imaging further confirmed that the zones of secreted siderophores and growth inhibition coincided. Moreover, either the repression of siderophore production or the neutralization of their iron-chelating activity led to increased microbial growth. Replacement of peptone by natural nitrogen sources regularly used as fertilizers such as ammonium nitrate, ammonium sulfate, sodium nitrate, and urea also triggered siderophore production in S. scabiei. The observed effect is not mediated by alkalinization of the medium as increasing the pH without providing additional nitrogen sources did not induce siderophore production. The nitrogen-induced siderophore production also inhibited the growth of important plant pathogens. Overall, our work suggests that not only the iron availability but also the nitrogen fertilizer sources could significantly impact the competition for iron between crop-colonizing microorganisms.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491266","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}
Iron (Fe) and Zinc (Zn) are essential micronutrients for plant growth and development. ZIP (ZRT, IRT-like protein) transporters, known for their role in the regulation of Zinc and Iron uptake, are pivotal in facilitating the absorption, transport, and maintenance of Fe/Zn homeostasis in plants. Nicotiana tabacum has been widely used as a model plant for gene function analysis; however, the tobacco ZIP genes have not been identified systematically. In this study, we have identified a comprehensive set of 32 NtZIP genes, which were phylogenetically categorized into three distinct clades. The gene structures, characterized by their exon/intron organization, and the protein motifs are relatively conserved, particularly among genes within the same clade. These NtZIP genes exhibit an uneven distribution across 12 chromosomes. The gene localization analysis revealed the presence of 11 pairs of homeologous locus genes and 7 pairs of tandem duplication genes within the genome. To further explore the functionality of these genes, real-time quantitative reverse transcription PCR was employed to assess their expression levels in roots subjected to metal deficiency. The results indicated that certain NtZIP genes are specifically upregulated in response to either Fe or Zn deficiency. Additionally, the presence of specific cis-elements within their promoter regions, such as the E-box associated with Fe deficiency response and the ZDRE box linked to Zn deficiency response, was identified. This study lays a foundational groundwork for future research into the biological functions of NtZIP genes in tobacco in micronutrient regulation and homeostasis.
{"title":"Genome-wide identification and expression analysis of the ZRT, IRT-like protein (ZIP) family in Nicotiana tabacum.","authors":"Zhijie Duan, Deka Reine Judesse Soviguidi, Bangzhen Pan, Rihua Lei, Zhongbang Song, Gang Liang","doi":"10.1093/mtomcs/mfae047","DOIUrl":"10.1093/mtomcs/mfae047","url":null,"abstract":"<p><p>Iron (Fe) and Zinc (Zn) are essential micronutrients for plant growth and development. ZIP (ZRT, IRT-like protein) transporters, known for their role in the regulation of Zinc and Iron uptake, are pivotal in facilitating the absorption, transport, and maintenance of Fe/Zn homeostasis in plants. Nicotiana tabacum has been widely used as a model plant for gene function analysis; however, the tobacco ZIP genes have not been identified systematically. In this study, we have identified a comprehensive set of 32 NtZIP genes, which were phylogenetically categorized into three distinct clades. The gene structures, characterized by their exon/intron organization, and the protein motifs are relatively conserved, particularly among genes within the same clade. These NtZIP genes exhibit an uneven distribution across 12 chromosomes. The gene localization analysis revealed the presence of 11 pairs of homeologous locus genes and 7 pairs of tandem duplication genes within the genome. To further explore the functionality of these genes, real-time quantitative reverse transcription PCR was employed to assess their expression levels in roots subjected to metal deficiency. The results indicated that certain NtZIP genes are specifically upregulated in response to either Fe or Zn deficiency. Additionally, the presence of specific cis-elements within their promoter regions, such as the E-box associated with Fe deficiency response and the ZDRE box linked to Zn deficiency response, was identified. This study lays a foundational groundwork for future research into the biological functions of NtZIP genes in tobacco in micronutrient regulation and homeostasis.</p>","PeriodicalId":89,"journal":{"name":"Metallomics","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398749","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}