Essays in biochemistry最新文献

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Phage-specific antibodies: are they a hurdle for the success of phage therapy? 噬菌体特异性抗体:它们是噬菌体疗法成功的障碍吗?
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-12-17 DOI: 10.1042/EBC20240024
Ayaka Washizaki, Arata Sakiyama, Hiroki Ando
{"title":"Phage-specific antibodies: are they a hurdle for the success of phage therapy?","authors":"Ayaka Washizaki, Arata Sakiyama, Hiroki Ando","doi":"10.1042/EBC20240024","DOIUrl":"10.1042/EBC20240024","url":null,"abstract":"<p><p>Phage therapy has attracted attention again owing to the increasing number of drug-resistant bacteria. Although the efficacy of phage therapy has been reported, numerous studies have indicated that the generation of phage-specific antibodies resulting from phage administration might have an impact on clinical outcomes. Phage-specific antibodies promote phage uptake by macrophages and contribute to their rapid clearance from the body. In addition, phage-specific neutralizing antibodies bind to the phages and diminish their antibacterial activity. Thus, phage-specific antibody production and its role in phage therapy have been analyzed both in vitro and in vivo. Strategies for prolonging the blood circulation time of phages have also been investigated. However, despite these efforts, the results of clinical trials are still inconsistent, and a consensus on whether phage-specific antibodies influence clinical outcomes has not yet been reached. In this review, we summarize the phage-specific antibody production during phage therapy. In addition, we introduce recently performed clinical trials and discuss whether phage-specific antibodies affect clinical outcomes and what we can do to further improve phage therapy regimens.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"633-644"},"PeriodicalIF":5.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652166/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282307","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
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 : 2024-12-17 DOI: 10.1042/EBC20240020
Robert T Schooley
{"title":"Translational research priorities for bacteriophage therapeutics.","authors":"Robert T Schooley","doi":"10.1042/EBC20240020","DOIUrl":"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":" ","pages":"621-631"},"PeriodicalIF":5.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652170/pdf/","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":"OA","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 : 2024-12-17 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":"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":" ","pages":"679-686"},"PeriodicalIF":5.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652150/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The new age of the phage. 噬菌体的新时代
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-12-17 DOI: 10.1042/EBC20240037
Joanne M Santini
{"title":"The new age of the phage.","authors":"Joanne M Santini","doi":"10.1042/EBC20240037","DOIUrl":"10.1042/EBC20240037","url":null,"abstract":"<p><p>The discovery of viruses that can devour bacteria, bacteriophages (phages), was in 1915. Phages are ubiquitous, outnumbering the organisms they devour, and genomically, morphologically, and ecologically diverse. They were critical in our development of molecular biology and biotechnology tools and have been used as therapeutics for over 100 years, primarily in Eastern Europe with thousands of patients from all over the world treated in Georgia. The rise of antimicrobial resistance and the lack of new antimicrobials, has brought them back into the spotlight dawning the New Age of the Phage. This special issue will provide further insight to phage diversity across ecosystems, including humans, animals, and plants, i.e. the basis of a One Health approach, and the requirements for turning phages into viable medicines for the many and not just for the few.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":"68 5","pages":"579-581"},"PeriodicalIF":5.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142834750","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
A comparative guide to expression systems for phage lysin production. 噬菌体溶酶生产表达系统比较指南。
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-12-17 DOI: 10.1042/EBC20240019
Emma Cremelie, Roberto Vázquez, Yves Briers
{"title":"A comparative guide to expression systems for phage lysin production.","authors":"Emma Cremelie, Roberto Vázquez, Yves Briers","doi":"10.1042/EBC20240019","DOIUrl":"10.1042/EBC20240019","url":null,"abstract":"<p><p>Phage lysins, bacteriophage-encoded enzymes tasked with degrading their host's cell wall, are increasingly investigated and engineered as novel antibacterials across diverse applications. Their rapid action, tuneable specificity, and low likelihood of resistance development make them particularly interesting. Despite numerous application-focused lysin studies, the art of their recombinant production remains relatively undiscussed. Here, we provide an overview of the available expression systems for phage lysin production and discuss key considerations guiding the choice of a suitable recombinant host. We systematically surveyed recent literature to evaluate the hosts used in the lysin field and cover various recombinant systems, including the well-known bacterial host Escherichia coli or yeast Saccharomyces cerevisiae, as well as plant, mammalian, and cell-free systems. Careful analysis of the limited studies expressing lysins in various hosts suggests a host-dependent effect on activity. Nonetheless, the multitude of available expression systems should be further leveraged to accommodate the growing interest in phage lysins and their expanding range of applications.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"645-659"},"PeriodicalIF":5.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11652153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282305","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
Sulfation pathways in times of change. 变化时代的磺化途径。
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-12-04 DOI: 10.1042/EBC20230099
Jonathan Wolf Mueller, Daniela Fietz, Irundika H K Dias
{"title":"Sulfation pathways in times of change.","authors":"Jonathan Wolf Mueller, Daniela Fietz, Irundika H K Dias","doi":"10.1042/EBC20230099","DOIUrl":"10.1042/EBC20230099","url":null,"abstract":"<p><p>Sulfation pathways are an essential part of overall sulfur metabolism. Sulfation pathways are mainly about sulfate activation, and the making and breaking of biological sulfate esters. This special issue features some extended reflection on what was presented at the SUPA 2023 meeting on Sulfation Pathways. Novel insights into the synthesis and analytics of sulfate, of sulfated conjugates, and of protein persulfides are presented. Oxysterol sulfates are presented as emerging sulfo-metabolites. Sulfation pathways enzymes are discussed in various disease settings. This special issue also presents insights into polysaccharide sulfotransferases and their functional characterization. Finally, cytoplasmic sulfotransferases are highlighted with regards to their impact on DNA-modification, and in the context of endocrine disruptors. All in all, thought-provoking findings, with the potential to guide and stimulate future research in the field of sulfation pathways and beyond.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":"68 4","pages":"379-382"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142767445","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
Oxysterol sulfates in fluids, cells and tissues: how much do we know about their clinical significance, biological relevance and biophysical implications? 体液、细胞和组织中的氧基甾醇硫酸盐:我们对其临床意义、生物学相关性和生物物理影响了解多少?
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-12-04 DOI: 10.1042/EBC20230090
Ana Reis, Irundika H K Dias
{"title":"Oxysterol sulfates in fluids, cells and tissues: how much do we know about their clinical significance, biological relevance and biophysical implications?","authors":"Ana Reis, Irundika H K Dias","doi":"10.1042/EBC20230090","DOIUrl":"10.1042/EBC20230090","url":null,"abstract":"<p><p>Oxysterol sulfates are emerging as key players in lipid homeostasis, inflammation and immunity. Despite this, knowledge on their basal levels in fluids, cells and tissues and any changes associated with age, gender and diet in health and disease; as well as their spatio-temporal distribution in cell membranes and organelles have been greatly hampered by the lack of commercially available pure synthetic standards. Expansion of the panel of pure oxysterol sulfates standards is pivotal to improve our understanding on the impact of oxysterol sulfates at the membrane level and their role in cellular events. While the clinical significance, biophysical implications and biological relevance of oxysterol sulfates in fluids, cells and tissues remains largely unknown, knowledge already gathered on the precursors of oxysterol sulfates (e.g. oxysterols and cholesterol sulfate) can be used to guide researchers on the most relevant aspects to search for when screening for oxysterol sulfates bioavailability in (patho)physiological conditions which are crucial in the design of biophysical and of cell-based assays. Herein, we provide a review on the brief knowledge involving oxysterol sulfate and an overview on the biophysical implications and biological relevance of oxysterols and cholesterol sulfate useful to redirect further investigations on the role of oxysterol sulfates in health and disease.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"401-410"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305299","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
Sulphotransferase-mediated toxification of chemicals in mouse models: effect of knockout or humanisation of SULT genes. 小鼠模型中亚硫酸盐转移酶介导的化学物质毒性:SULT基因敲除或人源化的影响。
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-12-04 DOI: 10.1042/EBC20240030
Hansruedi Glatt, Walter Meinl
{"title":"Sulphotransferase-mediated toxification of chemicals in mouse models: effect of knockout or humanisation of SULT genes.","authors":"Hansruedi Glatt, Walter Meinl","doi":"10.1042/EBC20240030","DOIUrl":"10.1042/EBC20240030","url":null,"abstract":"<p><p>Cytosolic sulphotransferase (SULT) enzymes catalyse reactions involved in xenobiotic elimination and hormone regulation. However, SULTs can also generate electrophilic reactive intermediates from certain substrates, including the activation of carcinogens. Here, we review toxicological studies of mouse strains with SULT status altered by genetic modification. Knockout mouse strains have been constructed for the enzymes Sult1a1, 1d1, 1e1, 2b1 and 4a1. In addition, transgenic strains are available for human SULT1A1/2. Among SULT knockout mouse strains, reduced fertility (Sult1e1) and early postnatal death (Sult4a1) were observed. In contrast, Sult1a1 or Sult1d1 knockouts and SULT1A1/2 transgenics were healthy and showed no obvious deficiencies. These strains were used in toxicological studies with 13 chemicals. Manipulation of the SULT system altered dramatically the adverse effects of many compounds; thus, very large differences in levels of DNA adducts formed in the liver or other tissues were seen with some chemicals - up to 99.2% decreases in knockouts and 83-fold increases in SULT1A1/2 transgenics. In many cases, these changes were restricted to the tissues in which the corresponding enzymes are expressed, arguing for local activation. However, with some compounds, the kidney was an important target tissue, due to the active transfer to that organ, via the circulation, of reactive sulphuric acid esters.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"523-539"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142750266","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
Quantification of persulfidation on specific proteins: are we nearly there yet? 特定蛋白质过硫化定量:我们快成功了吗?
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-12-04 DOI: 10.1042/EBC20230095
Hongling Liu, Florentina Negoita, Matthew Brook, Kei Sakamoto, Nicholas M Morton
{"title":"Quantification of persulfidation on specific proteins: are we nearly there yet?","authors":"Hongling Liu, Florentina Negoita, Matthew Brook, Kei Sakamoto, Nicholas M Morton","doi":"10.1042/EBC20230095","DOIUrl":"10.1042/EBC20230095","url":null,"abstract":"<p><p>Hydrogen sulfide (H2S) played a pivotal role in the early evolution of life on Earth before the predominance of atmospheric oxygen. The legacy of a persistent role for H2S in life's processes recently emerged through its discovery in modern biochemistry as an endogenous cellular signalling modulator involved in numerous biological processes. One major mechanism through which H2S signals is protein cysteine persulfidation, an oxidative post-translational modification. In recent years, chemoproteomic technologies have been developed to allow the global scanning of protein persulfidation targets in mammalian cells and tissues, providing a powerful tool to elucidate the broader impact of altered H2S in organismal physiological health and human disease states. While hundreds of proteins were confirmed to be persulfidated by global persulfidome methodologies, the targeting of specific proteins of interest and the investigation of further mechanistic studies are still underdeveloped due to a lack of stringent specificity of the methods and the inherent instability of persulfides. This review provides an overview of the processes of endogenous H2S production, oxidation, and signalling and highlights the application and limitations of current persulfidation labelling approaches for investigation of this important evolutionarily conserved biological switch for protein function.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"467-478"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282308","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
Cytosolic sulfotransferases in endocrine disruption. 内分泌紊乱中的细胞硫代转移酶
IF 5.6 2区 生物学
Essays in biochemistry Pub Date : 2024-12-04 DOI: 10.1042/EBC20230101
Michael W Duffel
{"title":"Cytosolic sulfotransferases in endocrine disruption.","authors":"Michael W Duffel","doi":"10.1042/EBC20230101","DOIUrl":"10.1042/EBC20230101","url":null,"abstract":"<p><p>The mammalian cytosolic sulfotransferases (SULTs) catalyze the sulfation of endocrine hormones as well as a broad array of drugs, environmental chemicals, and other xenobiotics. Many endocrine-disrupting chemicals (EDCs) interact with these SULTs as substrates and inhibitors, and thereby alter sulfation reactions responsible for metabolism and regulation of endocrine hormones such as estrogens and thyroid hormones. EDCs or their metabolites may also regulate expression of SULTs through direct interaction with nuclear receptors and other transcription factors. Moreover, some sulfate esters derived from EDCs (EDC-sulfates) may serve as ligands for endocrine hormone receptors. While the sulfation of an EDC can lead to its excretion in the urine or bile, it may also result in retention of the EDC-sulfate through its reversible binding to serum proteins and thereby enable transport to other tissues for intracellular hydrolysis and subsequent endocrine disruption. This mini-review outlines the potential roles of SULTs and sulfation in the effects of EDCs and our evolving understanding of these processes.</p>","PeriodicalId":11812,"journal":{"name":"Essays in biochemistry","volume":" ","pages":"541-553"},"PeriodicalIF":5.6,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849161","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
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