PROTEOMICS – Clinical Applications最新文献_第2页

Activity-Based Proteome Profiling of Serum Serine Hydrolases: Application in Pediatric Abusive Head Trauma. 基于活性的血清丝氨酸水解酶蛋白质组分析：在小儿头部创伤中的应用

IF 2.1 4区生物学

PROTEOMICS – Clinical Applications Pub Date : 2024-12-20 DOI: 10.1002/prca.202400022

Estelle Maret, Kim Wiskott, Tobias Shipley, Federica Gilardi, Marc Augsburger, Aurelien Thomas, Tony Fracasso, Tatjana Sajic

{"title":"Activity-Based Proteome Profiling of Serum Serine Hydrolases: Application in Pediatric Abusive Head Trauma.","authors":"Estelle Maret, Kim Wiskott, Tobias Shipley, Federica Gilardi, Marc Augsburger, Aurelien Thomas, Tony Fracasso, Tatjana Sajic","doi":"10.1002/prca.202400022","DOIUrl":"https://doi.org/10.1002/prca.202400022","url":null,"abstract":"Purpose: Traumatic brain injury (TBI), including pediatric abusive head trauma (AHT), is the leading cause of death and disability in children and young adults worldwide. The current understanding of trauma-induced molecular changes in the brain of human subjects with intracranial hemorrhage (ICH) remains inadequate and requires further investigation to improve the outcome and management of TBI in the clinic. Calcium-mediated damage at the site of brain injury has been shown to activate several catalytic enzymes.Experimental design: Serine hydrolases (SHs) are major catalytic enzymes involved in the biochemical pathways of blood coagulation, systemic inflammation, and neuronal signaling. Here, we investigated activity-based protein profiling (ABPP) coupled to liquid chromatography-mass spectrometry (LC-MS) by measuring the activity status of SH enzymes in the serum of infants with severe ICH as a consequence of AHT or atraumatic infants who died of sudden infant death syndrome (SIDS).Results: Our proof-of-principle study revealed significantly reduced physiological activity of dozens of metabolic SHs in the serum of infants with severe AHT compared to the SIDS group, with some of the enzymes being related to neurodevelopment and basic brain metabolism.Conclusions and clinical relevance: To our knowledge, this is the first study to investigate the ABPP of the SHs enzyme family to detect changes in their physiological activity in blood serum in severe TBI. We used antemortem (AM) serum from infants under the age of 2 years who were victims of AHT with a severe form of ICH. The analytical approach used in the proof-of-principle study shows reduced activities of serum serine lipases in AHT cases and could be further investigated in mild forms of AHT, which currently show 30% of misdiagnosed cases in clinics.","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400022"},"PeriodicalIF":2.1,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142865203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Computational Insight in the Identification of Non-Synonymous Single-Nucleotide Polymorphism Affecting the Structure and Function of Interleukin-4.

IF 2.1 4区生物学

PROTEOMICS – Clinical Applications Pub Date : 2024-12-08 DOI: 10.1002/prca.202400070

Pratima Roy, Siddharth Sharma, Manoj Baranwal

{"title":"Computational Insight in the Identification of Non-Synonymous Single-Nucleotide Polymorphism Affecting the Structure and Function of Interleukin-4.","authors":"Pratima Roy, Siddharth Sharma, Manoj Baranwal","doi":"10.1002/prca.202400070","DOIUrl":"https://doi.org/10.1002/prca.202400070","url":null,"abstract":"Background: IL4 is a versatile cytokine essentially known for differentiation, proliferation and cell death in cells. Its dysregulation has been found to be associated with the development of inflammatory disorders.Objective: The goal of the current investigation is to identify and select non-synonymous single-nucleotide polymorphisms (nsSNPs) in the IL-4 gene by employing computational methods which may have a potential functional impact on the occurrence of disease.Method and result: Six different nsSNPs were predicted to be deleterious based on the consensus of different algorithms: SIFT, Polyphen2 (Humdiv and HumVar), PredictSNP and SNP&GO. I-mutant and MuPro assessment revealed a decrease in the stability of these mutants except K150M. Modelling was then carried out to build the wild type along with its mutants, followed by superimposition of the wild type with mutants to evaluate the RMSD value, which lies between 0.26 and 0.34. Simulation results of mutant models, along with wild type, showed that four of the mutants (N113Y, A118G, R109W and K150M) deviated most and were unstable. A118G showed a significant deviation from the wild type, while V53A and C123R were stable.Conclusion: The finding establishes the evidence that the identified six nsSNPs of IL-4 can be the new entrant presenting their candidature for genetic testing.","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400070"},"PeriodicalIF":2.1,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142795054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Global Profiling of Protein Lactylation in Human Hippocampi.

IF 2.1 4区生物学

PROTEOMICS – Clinical Applications Pub Date : 2024-11-28 DOI: 10.1002/prca.202400061

Chun-Mei Shi, Qiao-Chu Wang, Xiao-Lu Li, Ye-Hong Yang, Xiao-Yue Tang, Yue Wu, Tao Ding, Xu-Tong Zhang, Zhi-Yi Zhang, Ron Han, Jie Kong, Jiang-Feng Liu, Jun-Tao Yang

{"title":"Global Profiling of Protein Lactylation in Human Hippocampi.","authors":"Chun-Mei Shi, Qiao-Chu Wang, Xiao-Lu Li, Ye-Hong Yang, Xiao-Yue Tang, Yue Wu, Tao Ding, Xu-Tong Zhang, Zhi-Yi Zhang, Ron Han, Jie Kong, Jiang-Feng Liu, Jun-Tao Yang","doi":"10.1002/prca.202400061","DOIUrl":"https://doi.org/10.1002/prca.202400061","url":null,"abstract":"Purpose: The hippocampus has long been associated with cognition and memory function, the implications of lysine lactylation (Kla), a recently identified post-translational modification (PTM), in the role of the hippocampus remain largely unexplored.Experimental design: An LC-MS/MS bottom-up proteomics analysis of three human hippocampal tissue samples was applied to profile the lactylation map in human hippocampi under normal physiological conditions.Results: We identified 2579 quantifiable Class I lactylated sites in 853 proteins, of which contained four types of modification motifs. Cellular localization analysis implies that a majority of lactylated proteins were distributed in the cytoplasm. Functional enrichment analysis showed that lactylated proteins were mainly involved in energy metabolic pathways. In addition, we found that the lactylation on histones exhibits a certain degree of conservation across different tissues. Compared with previously reported lactylation databases, 213 lactylated proteins were identified for the first time in this study.Conclusion and clinical relevance: The first global lactylated proteins atlas of human hippocampi was reported in this study. Our work provides a reliable foundation for further research on lactylation in the hippocampus under physiological conditions.","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400061"},"PeriodicalIF":2.1,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Characterization of the Metabolic Proteome of Serum From Patients With Diabetic Distal Symmetric Polyneuropathy. 糖尿病远端对称性多发性神经病患者血清代谢蛋白质组的特征

IF 2.1 4区生物学

PROTEOMICS – Clinical Applications Pub Date : 2024-11-01 Epub Date: 2024-09-23 DOI: 10.1002/prca.202300133

Hangping Zheng, Yue Gao, Xiaoming Zhu, Yuanpin Zhang, Yujia Li, Wanwan Sun, Lijin Ji, Xiaoxia Liu, Jie Zhang, Bin Lu, Yiming Li, Shuo Zhang

{"title":"Characterization of the Metabolic Proteome of Serum From Patients With Diabetic Distal Symmetric Polyneuropathy.","authors":"Hangping Zheng, Yue Gao, Xiaoming Zhu, Yuanpin Zhang, Yujia Li, Wanwan Sun, Lijin Ji, Xiaoxia Liu, Jie Zhang, Bin Lu, Yiming Li, Shuo Zhang","doi":"10.1002/prca.202300133","DOIUrl":"10.1002/prca.202300133","url":null,"abstract":"Aims: The pathophysiological of diabetic distal symmetric polyneuropathy (DSPN) remains to be elucidated and there are no diagnostic or prognostic biomarkers for the condition. In this explorative proteomic study, metabolic proteome profiling of serum in patients with/without DSPN was analyzed. We aimed to discover proteins with different abundance ranges through proximity extension assay (PEA) technology.Methods: Temperature quantitative sensory testing (QST) and electromyography (EMG) were used to access the small- and large-fiber function of all participants, respectively. The metabolic proteome profile of serum was analyzed using PEA technology (Olink Target 96 METABOLISM panel).Results: We evaluated serum from patients without DSPN (n = 27), with small-fiber neuropathy (SFN, n = 25) and with mixed small- and large-fiber neuropathy (MSLFN, n = 24). Fifteen proteins, which were especially related to immune response, insulin resistance, and lipid metabolism, were significantly different between patients without DSPN and with MSLFN. Besides, seven proteins, especially related to extracellular structure organization, were significantly different between serum from patients with SFN and with MSLFN. What's more, serum from patients without DSPN showed that three proteins, related to immune response, altered significantly compared to serum from patients with SFN.Conclusions: This was the first study that characterized the metabolic proteomic profile of serum in DSPN patients by analyzing a panel of 92 metabolic proteins using PEA technology.","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202300133"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Protein Network Alterations in G-CSF Treated Severe Congenital Neutropenia Patients and Beneficial Effects of Oral Health Intervention. 经 G-CSF 治疗的重度先天性中性粒细胞减少症患者的蛋白质网络变化及口腔健康干预的有益影响

IF 2.1 4区生物学

PROTEOMICS – Clinical Applications Pub Date : 2024-11-01 Epub Date: 2024-08-03 DOI: 10.1002/prca.202400064

Kai Bao, Angelika Silbereisen, Jonas Grossmann, Paolo Nanni, Peter Gehrig, Gülnur Emingil, Merve Erguz, Deniz Yilmaz Karapinar, Burç Pekpinarli, Georgios N Belibasakis, Georgios Tsilingaridis, Egija Zaura, Nagihan Bostanci

{"title":"Protein Network Alterations in G-CSF Treated Severe Congenital Neutropenia Patients and Beneficial Effects of Oral Health Intervention.","authors":"Kai Bao, Angelika Silbereisen, Jonas Grossmann, Paolo Nanni, Peter Gehrig, Gülnur Emingil, Merve Erguz, Deniz Yilmaz Karapinar, Burç Pekpinarli, Georgios N Belibasakis, Georgios Tsilingaridis, Egija Zaura, Nagihan Bostanci","doi":"10.1002/prca.202400064","DOIUrl":"10.1002/prca.202400064","url":null,"abstract":"Purpose: Severe congenital neutropenia (SCN) is a raredisorder characterized by diminished neutrophil levels. Despite granulocytecolony-stimulating factor (G-CSF) treatment, SCN patients remain still prone tosevere infections, including periodontal disease-a significant oral healthrisk. This study investigates the host proteome and metaproteome in saliva andgingival crevicular fluid (GCF) of G-CSF-treated patients.Experimental design: We used label-free quantitative proteomics on saliva and GCF samples from SCN patients before (n = 10, mean age: 10.7 ± 6.6 years) and after a 6-month oral hygiene intervention (n = 9,mean age: 11.6 ± 5.27 years), and from 12 healthy controls.Results: We quantified 894 proteins in saliva (648 human,246 bacterial) and 756 proteins in GCF (493 human, 263 bacterial). Predominant bacterial genera included Streptococcus, Veillonella, Selenomonas, Corynebacterium, Porphyromonas, and Prevotella. SCN patients showed reduced antimicrobial peptides (AMPs) and elevated complement proteins compared tohealthy controls. Oral hygiene intervention improved oral epithelial conditionsand reduced both AMPs and complement proteins.Conclusions and clinical relevance: SCN patients have aunique proteomic profile with reduced AMPs and increased complement proteins, contributing to infection susceptibility. Oral hygiene intervention not onlyimproved oral health in SCN patients but also offers potential overall therapeuticbenefits.","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400064"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Liver Tissue Proteins Improve the Accuracy of Plasma Proteins as Biomarkers in Diagnosing Metabolic Dysfunction-Associated Steatohepatitis. 肝组织蛋白提高了血浆蛋白作为生物标记物诊断代谢功能障碍相关性脂肪性肝炎的准确性

IF 2.1 4区生物学

PROTEOMICS – Clinical Applications Pub Date : 2024-11-01 Epub Date: 2024-07-28 DOI: 10.1002/prca.202300236

Achuthan Sourianarayanane, Michelle R Salemi, Brett S Phinney, Arthur J McCullough

{"title":"Liver Tissue Proteins Improve the Accuracy of Plasma Proteins as Biomarkers in Diagnosing Metabolic Dysfunction-Associated Steatohepatitis.","authors":"Achuthan Sourianarayanane, Michelle R Salemi, Brett S Phinney, Arthur J McCullough","doi":"10.1002/prca.202300236","DOIUrl":"10.1002/prca.202300236","url":null,"abstract":"Background: Biomarkers for metabolic dysfunction-associated steatohepatitis (MASH) have been considered based on proteomic and lipidomic data from plasma and liver tissue without clinical benefits. This study evaluated proteomics-based plasma and liver tissue biomarkers collected simultaneously from patients with metabolic dysfunction-associated steatotic liver disease (MASLD).Methods: Liver tissue and plasma samples were collected during liver biopsy to diagnose MASLD. Untargeted proteomics was performed on 64 patients.Results: Twenty plasma proteins were up- or downregulated in patients with MASH compared with those without MASH. The potential biomarkers utilizing the best combinations of these plasma proteins had an area under the receiver operating curve (AUROC) of 0.671 for detecting those with MASH compared with those without it. However, none of the 20 plasma proteins were represented among the significantly regulated liver tissue proteins in patients with MASH. Ten of them displayed a trend and relevance in liver tissue with MASLD progression. These 10 plasma proteins had an AUROC of 0.793 for MASH identification and higher positive and negative predictive values.Conclusion: The plasma and liver protein expressions of patients with MASH were not directly comparable. Plasma protein biomarkers that are also expressed in liver tissue can help improve MASH detection.","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202300236"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Analysis of Unfolded Protein Response Activation in Colon Adenocarcinoma Epithelial Cells: A Proteomic Study. 结肠腺癌上皮细胞中的折叠蛋白反应激活分析：蛋白质组学研究

IF 2.1 4区生物学

PROTEOMICS – Clinical Applications Pub Date : 2024-11-01 Epub Date: 2024-09-03 DOI: 10.1002/prca.202400008

Solange Vivier, Fabrice Bray, Stéphanie Flament, Lucile Guilbert, Florence Renaud, Christian Rolando, David Launay, Sylvain Dubucquoi, Vincent Sobanski

{"title":"Analysis of Unfolded Protein Response Activation in Colon Adenocarcinoma Epithelial Cells: A Proteomic Study.","authors":"Solange Vivier, Fabrice Bray, Stéphanie Flament, Lucile Guilbert, Florence Renaud, Christian Rolando, David Launay, Sylvain Dubucquoi, Vincent Sobanski","doi":"10.1002/prca.202400008","DOIUrl":"10.1002/prca.202400008","url":null,"abstract":"Purpose: High throughput technologies have identified molecular patterns in colorectal cancer (CRC) cells, aiding in modeling responses to anti-cancer treatments. The different responses observed depend on the type of cancer, the tumour grade and the functional programme of the cancer cells. Recent studies suggest that the unfolded protein response (UPR), autophagy and apoptosis could be involved in treatment resistance mechanisms by interacting with the tumour microenvironment (TME).Experimental design: We analysed by LC-MS/MS the proteome of two representative colon adenocarcinoma epithelial cell lines from different tumour grades (CCL-233 and CCL-221) at the basal state or after the UPR induction.Results: Cell lines expressed a different proteome on about 10% of their total proteins identified, especially on UPR, autophagy and apoptosis pathways proteins at basal state. After UPR induction, the proteome of the cells was modified with a greater adaptive response to cellular stress in CCL-221 cells where the UPR was strongly activated at the basal state.Conclusions and clinical relevance: CRC cell lines at different tumour grades expressed different functional programmes at the proteomic level and were characterised by different responses to the UPR induction. This study suggests that baseline cancer cell stress status could have an impact on the efficiency of cancer therapies.","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202400008"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Prospecting Specific Protein Patterns for High Body Mass Index (BMI), Metabolic Syndrome and Type 2 Diabetes in Saliva and Blood Plasma From a Brazilian Population. 探究巴西人口唾液和血浆中与高体重指数 (BMI)、代谢综合征和 2 型糖尿病有关的特定蛋白质模式。

IF 2.1 4区生物学

PROTEOMICS – Clinical Applications Pub Date : 2024-11-01 Epub Date: 2024-07-28 DOI: 10.1002/prca.202300238

Carlos Vinicius Ferreira da Silva, Carlos José Ferreira da Silva, Youssef Bacila Sade, Sandra Mara Naressi Scapin, Fabiano L Thompson, Cristiane Thompson, Carina Maciel da Silva-Boghossian, Eidy de Oliveira Santos

{"title":"Prospecting Specific Protein Patterns for High Body Mass Index (BMI), Metabolic Syndrome and Type 2 Diabetes in Saliva and Blood Plasma From a Brazilian Population.","authors":"Carlos Vinicius Ferreira da Silva, Carlos José Ferreira da Silva, Youssef Bacila Sade, Sandra Mara Naressi Scapin, Fabiano L Thompson, Cristiane Thompson, Carina Maciel da Silva-Boghossian, Eidy de Oliveira Santos","doi":"10.1002/prca.202300238","DOIUrl":"10.1002/prca.202300238","url":null,"abstract":"Purpose: Obesity and its associated metabolic disorders, such as T2DM and MeS, are a growing public health problem worldwide. Our goal was the identification of protein patterns that are uniquely characteristic of higher BMI, MeS, and T2DM in a Brazilian population.Experimental design: Saliva and plasma proteomes, clinical parameters were analyzed in a population from the state of Rio de Janeiro, Brazil, a mixed-race population. Volunteers were sorted by their BMI into normal (n = 29), overweight (n = 25), and obese (n = 15) and were compared with individuals with MeS (n = 23) and T2DM (n = 11).Results: The Random Forest (RF) predictive model revealed that three clinical variables, BMI, HOMA-IR, and fasting blood glucose, are most important for predicting MeS and T2DM. A total of six plasmatic proteins (ABCD4, LDB1, PDZ, podoplanin, lipirin-alpha-3, and WRS) and six salivary proteins (hemoglobin subunit beta, POTEE, T cell receptor alpha variable 9-2, lactotransferrin, cystatin-S, carbonic anhydrase 6), are enhanced in T2DM and in MeS.Conclusions and clinical relevance: Our data revealed similar alterations in protein composition across individuals with abnormal weight gain, T2DM, and MeS. This finding confirms the close link between these conditions at the molecular level in the studied population, potentially enhancing our understanding of these diseases and paving the way for the development of novel diagnostic tools.","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202300238"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Differential Abundance of Protein Acylation in Mycobacterium tuberculosis Under Exposure to Nitrosative Stress. 暴露于亚硝酸胁迫下的结核分枝杆菌蛋白质酰化的丰度差异

IF 2.1 4区生物学

PROTEOMICS – Clinical Applications Pub Date : 2024-11-01 Epub Date: 2024-07-31 DOI: 10.1002/prca.202300212

Alemayehu Godana Birhanu, Tahira Riaz, Mari Støen, Tone Tønjum

{"title":"Differential Abundance of Protein Acylation in Mycobacterium tuberculosis Under Exposure to Nitrosative Stress.","authors":"Alemayehu Godana Birhanu, Tahira Riaz, Mari Støen, Tone Tønjum","doi":"10.1002/prca.202300212","DOIUrl":"10.1002/prca.202300212","url":null,"abstract":"Background: Human macrophages generate antimicrobial reactive nitrogen species in response to infection by Mycobacterium tuberculosis (Mtb). Exposure to these redox-reactive compounds induces stress response in Mtb, which can affect posttranslational modifications (PTM).Methods: Here, we present the global analysis of the PTM acylation of Mtb proteins in response to a sublethal dose of nitrosative stress in the form of nitric oxide (NO) using label free quantification.Results: A total of 6437 acylation events were identified on 1496 Mtb proteins, and O-acylation accounted for 92.2% of the events identified, while 7.8% were N-acylation events. About 22% of the sites identified were found to be acylated by more than one acyl-group. Furthermore, the abundance of each acyl-group decreased as their molecular weight increased. Quantitative PTM analysis revealed differential abundance of acylation in proteins involved in stress response, iron ion homeostasis, growth, energy metabolism, and antimicrobial resistance (AMR) induced by nitrosative stress over time.Conclusions: The results reveal a potential role of Mtb protein acylation in the bacterial stress responses and AMR. To our knowledge, this is the first report on global O-acylation profile of Mtb in response to NO. This will significantly improve our understanding of the changes in Mtb acylation under nitrosative stress, highly relevant for global health.","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202300212"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Mass Spectrometric and Artificial Intelligence-Based Identification of the Secretome of Plasmodium falciparum Merozoites to Provide Novel Candidates for Vaccine Development Pipeline. 基于质谱和人工智能的恶性疟原虫有尾孢子虫分泌组鉴定，为疫苗开发提供新的候选方案。

IF 2.1 4区生物学

PROTEOMICS – Clinical Applications Pub Date : 2024-11-01 Epub Date: 2024-07-31 DOI: 10.1002/prca.202300115

Akshay Munjal, Devasahayam Arokia Balaya Rex, Prachi Garg, Thottethodi Subrahmanya Keshava Prasad, Sai Kumar Mishra, Yuktika Malhotra, Deepika Yadav, Jerry John, Preeti P, Kamal Rawal, Shailja Singh

{"title":"Mass Spectrometric and Artificial Intelligence-Based Identification of the Secretome of Plasmodium falciparum Merozoites to Provide Novel Candidates for Vaccine Development Pipeline.","authors":"Akshay Munjal, Devasahayam Arokia Balaya Rex, Prachi Garg, Thottethodi Subrahmanya Keshava Prasad, Sai Kumar Mishra, Yuktika Malhotra, Deepika Yadav, Jerry John, Preeti P, Kamal Rawal, Shailja Singh","doi":"10.1002/prca.202300115","DOIUrl":"10.1002/prca.202300115","url":null,"abstract":"Purpose: Merozoites are the only extracellular form of blood stage parasites, making it a worthwhile target. Multiple invasins that are stored in the merozoite apical organelles, are secreted just prior to invasion, and mediates its interaction with RBC. A comprehensive identification of all these secreted invasins is lacking and this study addresses that gap.Experimental design: Pf3D7 merozoites were enriched and triggered to discharge apical organelle contents by exposure to ionic conditions mimicking that of blood plasma. The secreted proteins were separated from cellular contents and both the fractions were subjected to proteomic analysis. Also, the identified secreted proteins were subjected to GO, PPI network analysis, and AI-based in silico approach to understand their vaccine candidacy.Results: A total of 63 proteins were identified in the secretory fraction with membrane and apical organellar localization. This includes various MSPs, micronemal EBAs and rhoptry bulb proteins, which play a crucial role in initial and late merozoite attachment, and majority of them qualified as vaccine candidates.Conclusion and clinical relevance: We, for the first time, report the secretory repertoire of merozoite and its status for vaccine candidacy. This information can be utilized to develop better invasion blocking multisubunit vaccines, comprising of immunological epitopes from several secreted invasins.","PeriodicalId":20571,"journal":{"name":"PROTEOMICS – Clinical Applications","volume":" ","pages":"e202300115"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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