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Phage diversity in One Health. 同一健康中的噬菌体多样性
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-10-30 DOI: 10.1042/EBC20240012
Hannah V Pye, Revathy Krishnamurthi, Ryan Cook, Evelien M Adriaenssens
{"title":"Phage diversity in One Health.","authors":"Hannah V Pye, Revathy Krishnamurthi, Ryan Cook, Evelien M Adriaenssens","doi":"10.1042/EBC20240012","DOIUrl":"https://doi.org/10.1042/EBC20240012","url":null,"abstract":"<p><p>One Health aims to bring together human, animal, and environmental research to achieve optimal health for all. Bacteriophages (phages) are viruses that kill bacteria and their utilisation as biocontrol agents in the environment and as therapeutics for animal and human medicine will aid in the achievement of One Health objectives. Here, we assess the diversity of phages used in One Health in the last 5 years and place them in the context of global phage diversity. Our review shows that 98% of phages applied in One Health belong to the class Caudoviricetes, compared to 85% of sequenced phages belonging to this class. Only three RNA phages from the realm Riboviria have been used in environmental biocontrol and human therapy to date. This emphasises the lack in diversity of phages used commercially and for phage therapy, which may be due to biases in the methods used to both isolate phages and select them for applications. The future of phages as biocontrol agents and therapeutics will depend on the ability to isolate genetically novel dsDNA phages, as well as in improving efforts to isolate ssDNA and RNA phages, as their potential is currently undervalued. Phages have the potential to reduce the burden of antimicrobial resistance, however, we are underutilising the vast diversity of phages present in nature. More research into phage genomics and alternative culture methods is required to fully understand the complex relationships between phages, their hosts, and other organisms in the environment to achieve optimal health for all.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Considerations for prioritising clinical research using bacteriophage. 利用噬菌体进行临床研究的优先考虑因素。
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-10-30 DOI: 10.1042/EBC20240013
Sarah J L Edwards, Yiran Tao, Rodas Elias, Robert Schooley
{"title":"Considerations for prioritising clinical research using bacteriophage.","authors":"Sarah J L Edwards, Yiran Tao, Rodas Elias, Robert Schooley","doi":"10.1042/EBC20240013","DOIUrl":"https://doi.org/10.1042/EBC20240013","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) poses a significant global health threat, as it contributes to prolonged illness, higher mortality rates and increased healthcare costs. As traditional antibiotics become less effective, treatments such as bacteriophage therapy offer potential solutions. The question remains, however, on how to set research priorities in the face of a growing number of antibiotic-resistant pathogens, some common and/or dangerous. One standard way of making decisions about which research to prioritise is by using the disability-adjusted life year metric to estimate the current global impact of a disease or condition, combined with considerations of social justice although decisions made at a national level by governments, especially in low income countries with forecasting potential over future needs may look very different. Another approach is based on the needs of researchers and regulators given what we know about the technology itself. The biological characteristics of bacteriophage therapies set challenges to a universal and standardised prioritisation method. A proof of principle is still arguably needed. With a preliminary discussion of the scope and complexity of AMR and AMR therapeutics, we propose some implications of regulatory frameworks aiming to integrate bacteriophage therapy into mainstream medical practice while gathering scientific data on safety and efficacy, enhancing the collective action needed to combat AMR.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Understanding metabolic plasticity at single cell resolution. 以单细胞分辨率了解代谢可塑性。
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-10-28 DOI: 10.1042/EBC20240002
Christina C Abbate, Jason Hu, John G Albeck
{"title":"Understanding metabolic plasticity at single cell resolution.","authors":"Christina C Abbate, Jason Hu, John G Albeck","doi":"10.1042/EBC20240002","DOIUrl":"10.1042/EBC20240002","url":null,"abstract":"<p><p>It is increasingly clear that cellular metabolic function varies not just between cells of different tissues, but also within tissues and cell types. In this essay, we envision how differences in central carbon metabolism arise from multiple sources, including the cell cycle, circadian rhythms, intrinsic metabolic cycles, and others. We also discuss and compare methods that enable such variation to be detected, including single-cell metabolomics and RNA-sequencing. We pay particular attention to biosensors for AMPK and central carbon metabolites, which when used in combination with metabolic perturbations, provide clear evidence of cellular variance in metabolic function.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Translational research priorities for bacteriophage therapeutics. 噬菌体疗法的转化研究重点。
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-10-17 DOI: 10.1042/EBC20240020
Robert T Schooley
{"title":"Translational research priorities for bacteriophage therapeutics.","authors":"Robert T Schooley","doi":"10.1042/EBC20240020","DOIUrl":"https://doi.org/10.1042/EBC20240020","url":null,"abstract":"<p><p>The growing threat of antimicrobial resistant (AMR) bacterial pathogens coupled with the relative dearth of promising novel antibiotics requires the discovery and development additional medical interventions. Over the past decade bacteriophages have emerged one of the most promising new tools to combat AMR pathogens. Anecdotal clinical experiences under so-called 'compassionate use' regulatory pathways as well as a limited number of clinical trials have provided ample evidence of safety and early evidence of efficacy. For phages to reach their full potential it is critical that rigorous clinical trials be conducted that define their optimal use and that enable regulatory authorities to support the commercialization required to afford global access. The clinical development of phage therapeutics requires the design and execution of clinical trials that take full advantage of lessons learned from a century of antibiotic development and that use clinical investigation as a platform in which aspects of phage biology that are critical to therapeutics are more clearly elucidated. Translational research that elucidates phage biology in the context of clinical trials will promote highly relevant hypothesis-driven work in basic science laboratories and will greatly accelerate the development of the field of phage therapeutics.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Catalytic mechanism and kinetics of malate dehydrogenase. 苹果酸脱氢酶的催化机制和动力学。
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230086
Laura de Lorenzo, Tyler M M Stack, Kristin M Fox, Katherine M Walstrom
{"title":"Catalytic mechanism and kinetics of malate dehydrogenase.","authors":"Laura de Lorenzo, Tyler M M Stack, Kristin M Fox, Katherine M Walstrom","doi":"10.1042/EBC20230086","DOIUrl":"10.1042/EBC20230086","url":null,"abstract":"<p><p>Malate dehydrogenase (MDH) is a ubiquitous and central enzyme in cellular metabolism, found in all kingdoms of life, where it plays vital roles in the cytoplasm and various organelles. It catalyzes the reversible NAD+-dependent reduction of L-malate to oxaloacetate. This review describes the reaction mechanism for MDH and the effects of mutations in and around the active site on catalytic activity and substrate specificity, with a particular focus on the loop that encloses the active site after the substrates have bound. While MDH exhibits selectivity for its preferred substrates, mutations can alter the specificity of MDH for each cosubstrate. The kinetic characteristics and similarities of a variety of MDH isozymes are summarized, and they illustrate that the KM values are consistent with the relative concentrations of the substrates in cells. As a result of its existence in different cellular environments, MDH properties vary, making it an attractive model enzyme for studying enzyme activity and structure under different conditions.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Malate dehydrogenase in parasitic protozoans: roles in metabolism and potential therapeutic applications. 寄生原生动物中的苹果酸脱氢酶:在新陈代谢中的作用和潜在的治疗应用。
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230075
Amy L Springer, Swati Agrawal, Eric P Chang
{"title":"Malate dehydrogenase in parasitic protozoans: roles in metabolism and potential therapeutic applications.","authors":"Amy L Springer, Swati Agrawal, Eric P Chang","doi":"10.1042/EBC20230075","DOIUrl":"10.1042/EBC20230075","url":null,"abstract":"<p><p>The role of malate dehydrogenase (MDH) in the metabolism of various medically significant protozoan parasites is reviewed. MDH is an NADH-dependent oxidoreductase that catalyzes interconversion between oxaloacetate and malate, provides metabolic intermediates for both catabolic and anabolic pathways, and can contribute to NAD+/NADH balance in multiple cellular compartments. MDH is present in nearly all organisms; isoforms of MDH from apicomplexans (Plasmodium falciparum, Toxoplasma gondii, Cryptosporidium spp.), trypanosomatids (Trypanosoma brucei, T. cruzi) and anaerobic protozoans (Trichomonas vaginalis, Giardia duodenalis) are presented here. Many parasitic species have complex life cycles and depend on the environment of their hosts for carbon sources and other nutrients. Metabolic plasticity is crucial to parasite transition between host environments; thus, the regulation of metabolic processes is an important area to explore for therapeutic intervention. Common themes in protozoan parasite metabolism include emphasis on glycolytic catabolism, substrate-level phosphorylation, non-traditional uses of common pathways like tricarboxylic acid cycle and adapted or reduced mitochondria-like organelles. We describe the roles of MDH isoforms in these pathways, discuss unusual structural or functional features of these isoforms relevant to activity or drug targeting, and review current studies exploring the therapeutic potential of MDH and related genes. These studies show that MDH activity has important roles in many metabolic pathways, and thus in the metabolic transitions of protozoan parasites needed for success as pathogens.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11461325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Malate dehydrogenase in plants: evolution, structure, and a myriad of functions. 植物中的苹果酸脱氢酶:进化、结构和多种功能。
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230089
Lisa M Baird, Christopher E Berndsen, Jonathan D Monroe
{"title":"Malate dehydrogenase in plants: evolution, structure, and a myriad of functions.","authors":"Lisa M Baird, Christopher E Berndsen, Jonathan D Monroe","doi":"10.1042/EBC20230089","DOIUrl":"10.1042/EBC20230089","url":null,"abstract":"<p><p>Malate dehydrogenase (MDH) catalyzes the interconversion of oxaloacetate and malate coupled to the oxidation/reduction of coenzymes NAD(P)H/NAD(P)+. While most animals have two isoforms of MDH located in the cytosol and mitochondria, all major groups of land plants have at least six MDHs localized to the cytosol, mitochondria, plastids, and peroxisomes. This family of enzymes participates in important reactions in plant cells including photosynthesis, photorespiration, lipid metabolism, and NH4+ metabolism. MDH also helps to regulate the energy balance in the cell and may help the plant cope with various environmental stresses. Despite their functional diversity, all of the plant MDH enzymes share a similar structural fold and act as dimers. In this review, we will introduce readers to our current understanding of the plant MDHs, including their evolution, structure, and function. The focus will be on the MDH enzymes of the model plant Arabidopsis thaliana.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Phosphorylation of mammalian cytosolic and mitochondrial malate dehydrogenase: insights into regulation. 哺乳动物细胞质和线粒体苹果酸脱氢酶的磷酸化:对调控的见解。
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230079
Joseph J Provost, Kathleen A Cornely, Pamela S Mertz, Celeste N Peterson, Sophie G Riley, Harrison J Tarbox, Shree R Narasimhan, Andrew J Pulido, Amy L Springer
{"title":"Phosphorylation of mammalian cytosolic and mitochondrial malate dehydrogenase: insights into regulation.","authors":"Joseph J Provost, Kathleen A Cornely, Pamela S Mertz, Celeste N Peterson, Sophie G Riley, Harrison J Tarbox, Shree R Narasimhan, Andrew J Pulido, Amy L Springer","doi":"10.1042/EBC20230079","DOIUrl":"10.1042/EBC20230079","url":null,"abstract":"<p><p>Malate dehydrogenase (MDH) is a key enzyme in mammalian metabolic pathways in cytosolic and mitochondrial compartments. Regulation of MDH through phosphorylation remains an underexplored area. In this review we consolidate evidence supporting the potential role of phosphorylation in modulating the function of mammalian MDH. Parallels are drawn with the phosphorylation of lactate dehydrogenase, a homologous enzyme, to reveal its regulatory significance and to suggest a similar regulatory strategy for MDH. Comprehensive mining of phosphorylation databases, provides substantial experimental (primarily mass spectrometry) evidence of MDH phosphorylation in mammalian cells. Experimentally identified phosphorylation sites are overlaid with MDH's functional domains, offering perspective on how these modifications could influence enzyme activity. Preliminary results are presented from phosphomimetic mutations (serine/threonine residues changed to aspartate) generated in recombinant MDH proteins serving as a proof of concept for the regulatory impact of phosphorylation. We also examine and highlight several approaches to probe the structural and cellular impact of phosphorylation. This review highlights the need to explore the dynamic nature of MDH phosphorylation and calls for identifying the responsible kinases and the physiological conditions underpinning this modification. The synthesis of current evidence and experimental data aims to provide insights for future research on understanding MDH regulation, offering new avenues for therapeutic interventions in metabolic disorders and cancer.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetics of MDH in humans. 人类 MDH 遗传学。
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230078
Adam Haberman, Celeste N Peterson
{"title":"Genetics of MDH in humans.","authors":"Adam Haberman, Celeste N Peterson","doi":"10.1042/EBC20230078","DOIUrl":"10.1042/EBC20230078","url":null,"abstract":"<p><p>Malate dehydrogenase (MDH) performs key roles in metabolism, but little is known about its function specifically in human health and disease. In this minireview, we describe the incomplete state of our knowledge of human MDH genetics. Humans have three MDH genes with a total of four validated isoforms. MDH1 and MDH2 are widely expressed, while MDH1B is only expressed in a small subset of tissues. Many mutations in MDH1 and MDH2 have been identified in patients, but only a few have been studied to determine what symptoms they cause. MDH1 has been associated with cancer and a neurodevelopmental disorder. MDH2 has been associated with diabetes, neurodevelopmental disorders, and cancer.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Malate dehydrogenase (MDH) in cancer: a promiscuous enzyme, a redox regulator, and a metabolic co-conspirator. 癌症中的苹果酸脱氢酶(MDH):一种杂合酶、氧化还原调节器和代谢共谋者。
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-10-03 DOI: 10.1042/EBC20230088
Betsy Leverett, Shane Austin, Jason Tan-Arroyo
{"title":"Malate dehydrogenase (MDH) in cancer: a promiscuous enzyme, a redox regulator, and a metabolic co-conspirator.","authors":"Betsy Leverett, Shane Austin, Jason Tan-Arroyo","doi":"10.1042/EBC20230088","DOIUrl":"10.1042/EBC20230088","url":null,"abstract":"<p><p>Malate dehydrogenase (MDH) is an essential enzyme in the tricarboxylic acid cycle that functions in cellular respiration and redox homeostasis. Recent studies indicate that MDH facilitates metabolic plasticity in tumor cells, catalyzing the formation of an oncometabolite, contributing to altered epigenetics, and maintaining redox capacity to support the rewired energy metabolism and biosynthesis that enables cancer progression. This minireview summarizes current findings on the unique supporting roles played by MDH in human cancers and provides an update on targeting MDH in cancer chemotherapy.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":null,"pages":null},"PeriodicalIF":5.6,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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