Article
Immunology
Hong Wang, Li Wan, Jiahui Shi, Tao Zhang, Huiming Zhu, Songhao Jiang, Shuhong Meng, Shujia Wu, Jinshuai Sun, Lei Chang, Liqun Zhang, Kanglin Wan, Jiaqi Yang, Xiuqin Zhao, Haican Liu, Yao Zhang, Erhei Dai, Ping Xu
Summary: Different strains of Mycobacterium tuberculosis complex (MTBC) exhibit high similarity but show differences in virulence, immune response, and transmissibility. Proteomic analysis of virulent H37Rv, attenuated H37Ra, and avirulent M. bovis BCG vaccine strains revealed minimal expression differences between H37Ra and H37Rv in different growth phases, while significant dysregulation was observed in H37Ra and H37Rv during log phase. Differences were also noted between BCG and H37Rv, as well as BCG and H37Ra during the stationary phase. Protein abundance patterns were similar between H37Ra and BCG, and between H37Rv and H37Ra in different growth phases. Upregulated proteins in H37Rv and H37Ra during log phase were found to be virulence-related, while dysregulated proteins in BCG were identified as M. tuberculosis response proteins under dormancy conditions. This study provides insights into the pathogenesis of H37Rv, attenuation of H37Ra, and immune protection of BCG.
Review
Microbiology
Manikuntala Kundu, Joyoti Basu
Summary: Mycobacterium tuberculosis can survive in its host for extended periods, remaining dormant within granulomas. Understanding the mechanisms of entry into and exit from dormancy is crucial for developing new tuberculosis treatment strategies. Transcriptomic and proteomic approaches have revealed key genes and pathways involved in dormancy and reactivation of M. tuberculosis.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Microbiology
Nadeem Ullah, Ling Hao, Jo-Lewis Banga Ndzouboukou, Shiyun Chen, Yaqi Wu, Longmeng Li, Eman Borham Mohamed, Yangbo Hu, Xionglin Fan
Summary: Rifampicin is a key first-line drug against tuberculosis, with specific protein expression differences identified in rifampicin-resistant strains related to cell wall and cell processes. Differential protein regulation in resistant strains highlights potential targets for effective management of drug-resistant tuberculosis.
Article
Biotechnology & Applied Microbiology
Ya Zheng, Bin Mao, Qian Wang, Xin Duan, Meng-Yan Chen, Wei Shen, Chao Li, Yu-Feng Wang
Summary: Knockdown of ocn gene in Drosophila testes resulted in smaller testis without germ cells. Through proteomics sequencing, 606 proteins were identified as significantly changed in expression after ocn knockdown. The down-regulation of ocn disturbed key signaling pathways related to cell survival and differentiation.
Article
Pharmacology & Pharmacy
Rami Ayoun Alsoud, Robin J. J. Svensson, Elin M. M. Svensson, Stephen H. H. Gillespie, Martin J. J. Boeree, Andreas H. H. Diacon, Rodney Dawson, Rob E. E. Aarnoutse, Ulrika S. H. Simonsson
Summary: This study aimed to develop a combined quantitative tuberculosis biomarker model for assessing drug efficacy in early bactericidal activity studies. By using CFU and TTP data simultaneously, the model provides an efficient approach to evaluate drug efficacy and describe the relationship between CFU and TTP over time.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Immunology
Catherine Vilcheze, Bo Yan, Rosalyn Casey, Suzie Hingley-Wilson, Laurence Ettwiller, William R. Jacobs
Summary: This study provides detailed insights into the transcriptome changes of Mycobacterium tuberculosis under persisting stresses, highlighting genes and gene cohorts involved in stress response. These findings are valuable for the design of novel drug targets and vaccine development.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Microbiology
Margarita Villar, Rajesh Man Rajbhandari, Sara Artigas-Jeronimo, Marinela Contreras, Amir Sadaula, Dibesh Karmacharya, Paulo Celio Alves, Christian Gortazar, Jose de la Fuente
Summary: This study aimed to identify proteins related to tuberculosis infection in Asian elephants using a serum proteomics approach. The results revealed 26 dysregulated proteins in response to tuberculosis infection, including both immunoglobulin and non-immunoglobulin proteins. These findings provide new information on the antibody response and protective mechanisms against tuberculosis in Asian elephants, and offer potential biomarkers for diagnostic and control purposes.
Article
Infectious Diseases
Enyu Tong, Ying Zhou, Zhengwei Liu, Yelei Zhu, Mingwu Zhang, Kunyang Wu, Junhang Pan, Jianmin Jiang
Summary: This study aimed to determine the prevalence and molecular characterization of bedaquiline resistance among rifampicin-resistant tuberculosis isolates in Zhejiang, China. The results showed that bedaquiline exhibited strong antibacterial activity against rifampicin-resistant tuberculosis isolates, and the Rv0678 gene was identified as the primary mechanism contributing to bedaquiline resistance in Zhejiang, China.
INFECTION AND DRUG RESISTANCE
(2023)
Review
Microbiology
Elena G. Salina, Vadim Makarov
Summary: Both latent and active TB infections are caused by a heterogeneous population of mycobacteria, and understanding the mechanisms underlying dormant and resuscitation phases of M. tuberculosis can help control latent infection and prevent transmission.
Article
Gastroenterology & Hepatology
Soo Young Cho, Heeyoun Hwang, Yun-Hee Kim, Byong Chul Yoo, Nayoung Han, Sun-Young Kong, Min-Jeong Baek, Kyung-Hee Kim, Mi Rim Lee, Jae Gwang Park, Sung-Sik Han, Woo Jin Lee, Charny Park, Jong Bae Park, Jin Young Kim, Sang-Jae Park, Sang Myung Woo
Summary: Through comprehensive analysis of genomic, transcriptomic, proteomic, and phosphoproteomic data from 102 iCC patients, three clinically supported subtypes were identified (stem-like, poorly immunogenic, and metabolism), and an organoid model was constructed for therapeutic testing. The ALDH1A1 inhibitor NCT-501 showed synergy with nanoparticle albumin-bound-paclitaxel in the organoid model for the stem-like subtype. Dysregulations in oncometabolites were associated with different clinical outcomes in the stem-like and metabolism subtypes. The poorly immunogenic subtype exhibited non-T-cell tumor infiltration. Integrated multiomics analysis reproduced the 3 subtypes and revealed heterogeneity in iCC.
Article
Biochemistry & Molecular Biology
Zoheir B. Demmouche, Jacques J. Tremblay
Summary: Leydig cells produce testosterone, a hormone essential for male sex differentiation and spermatogenesis. LH stimulates testosterone production by activating various kinases and transcription factors through increasing cAMP levels. AMPK, activated by AMP, potently represses steroidogenesis. The study identifies global changes in protein and phosphoprotein levels during both the stimulatory and inhibitory phases of steroidogenesis, providing new insights into the finely tuned processes of adequate steroid hormone production.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Barbara Tizzano, Tobias K. Dallenga, Christian Utpatel, Jochen Behrends, Susanne Homolka, Thomas A. Kohl, Stefan Niemann
Summary: The study reveals that survival and recovery from oxygen starvation in different strains of Mycobacterium tuberculosis are lineage-dependent, with strains belonging to the Euro-American lineage (L4) demonstrating similar survival and resuscitation characteristics, while strains from other lineages show varied responses to oxygen starvation. The findings suggest that resuscitation after oxygen starvation is not a universal feature of all M. tuberculosis strains.
SCIENTIFIC REPORTS
(2021)
Article
Nutrition & Dietetics
Rebecca Hetz, Erik Beeler, Alexis Janoczkin, Spencer Kiers, Ling Li, Belinda B. Willard, Mohammed S. Razzaque, Ping He
Summary: In this study, proteomics and phosphoproteomics were used to analyze the effects of Pi on protein abundance and phosphorylation. The results revealed that Pi affected signaling pathways and various biological processes. Western blot analysis confirmed changes in protein level and phosphorylation of key regulators involved in pre-mRNA alternative splicing. The global proteome and phospho-profiling provided insights into the cell signaling networks rewired by excessive Pi and improved our understanding of the molecular mechanisms of phosphate toxicity.
FRONTIERS IN NUTRITION
(2022)
Article
Medicine, Research & Experimental
Jonas Bossart, Alexandra Rippl, Amy E. Barton Alston, Beat Fluehmann, Reinaldo Digigow, Marija Buljan, Vanesa Ayala-Nunez, Peter Wick
Summary: Macrophages play a crucial role in the uptake and metabolism of iron-carbohydrate complexes. The mechanisms by which these complexes are taken up and metabolized by macrophages are not fully understood. Using a proteomics approach, researchers found that iron sucrose alters the expression of multiple receptors and can be used as a source of iron for macrophages. However, excessive iron can cause oxidative stress. Additionally, the surface characteristics of iron-carbohydrate complexes may influence cell responses.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Ritesh R. Sevalkar, Joel N. Glasgow, Martin Pettinati, Marcelo A. Marti, Vineel P. Reddy, Swati Basu, Elmira Alipour, Daniel B. Kim-Shapiro, Dario A. Estrin, Jack R. Lancaster, Adrie J. C. Steyn
Summary: This study reveals that Mycobacterium tuberculosis can sense and respond to hydrogen sulfide (H2S) signal via the DosS/T/R system. The binding of H2S to DosS heme iron increases DosS autokinase activity and subsequent phosphorylation of DosR, leading to the modulation of gene expression. These findings demonstrate a novel mechanism for Mtb to sense and respond to H2S and highlight the remarkable plasticity of DosS.
Article
Multidisciplinary Sciences
Dylan P. Noone, Douwe J. Dijkstra, Teun T. van der Klugt, Peter A. van Veelen, Arnoud H. de Ru, Paul J. Hensbergen, Leendert A. Trouw, Thomas H. Sharp
Summary: This study presents a high-resolution structure of the prototypical long pentraxin, PTX3, and reveals a radically different quaternary structure compared to other pentraxins. The structure was obtained using cryo-electron microscopy (cryo-EM) and AlphaFold prediction. The resulting structure provides insights into ligand binding sites and can potentially inform the development of therapies for conditions such as COVID-19, cancer, and female infertility.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Oncology
Rosa A. van Amerongen, Renate S. Hagedoorn, Dennis F. G. Remst, Danique C. Assendelft, Dirk M. van der Steen, Anne K. Wouters, Marian van de Meent, Michel G. D. Kester, Arnoud H. de Ru, Marieke Griffioen, Peter A. van Veelen, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: In this study, high-avidity WT1-specific T cells were identified from the allogeneic T-cell repertoire of healthy donors. These T cells showed potent and specific anti-WT1 activity against newly identified WT1 peptides derived from primary leukemia and ovarian carcinoma samples. Additionally, T-cell clones with T-cell receptor (TCR) gene transfer showed antitumor reactivity against WT1-expressing solid tumor cell lines, acute myeloid leukemia (AML) blasts, and ovarian carcinoma patient samples. These findings suggest that these TCRs and naturally expressed WT1 peptides have potential for TCR gene transfer strategies in patients with WT1-expressing tumors, including AML and ovarian carcinoma.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Immunology
Paula Ruibal, Kees L. M. C. Franken, Krista E. vzn Meijgaarden, Marjolein van Wolfswinkel, Ian Derksen, Ferenc A. Scheeren, George M. C. Janssen, Peter A. van Veelen, Charlotte Sarfas, Andrew D. White, Sally A. Sharpe, Fabrizio Palmieri, Linda Petrone, Delia Goletti, Thomas Abeel, Tom H. M. Ottenhoff, Simone A. Joosten
Summary: Tuberculosis remains a deadly infectious disease worldwide, causing significant social and economic burden. This study developed an improved algorithm to identify Mycobacterium tuberculosis-derived peptides that can activate specific HLA-E-restricted T cells.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Orthopedics
M. Tuerlings, G. M. C. Janssen, I. Boone, M. van Hoolwerff, A. Rodriguez Ruiz, E. Houtman, H. E. D. Suchiman, R. J. P. van der Wal, R. G. H. H. Nelissen, R. Coutinho de Almeida, P. A. van Veelen, Y. F. M. Ramos, I. Meulenbelt
Summary: The study aims to explore the co-expression network of the osteoarthritis (OA) risk gene WWP2 in articular cartilage and examine the cartilage characteristics when mimicking the effect of OA risk allele rs1052429-A on WWP2 expression in a human 3D in vitro model of cartilage. The study found 98 highly correlated genes in lesioned OA cartilage when performing Spearman correlations. Upregulation of WWP2 in 3D chondrocyte pellet cultures resulted in changes in the expression of various genes and proteins related to cartilage matrix deposition. Additionally, miR-140 was found to be involved in similar pathways as WWP2.
OSTEOARTHRITIS AND CARTILAGE
(2023)
Article
Immunology
W. J. Venema, S. Hiddingh, G. M. C. Janssen, J. Ossewaarde-van Norel, N. Dam van Loon, J. H. de Boer, P. A. van Veelen, J. J. W. Kuiper
Summary: This study identified the naturally presented antigenic SAG peptides through HLA-A29 immunopeptidomics and found that SAG is not a CD8+ T cell autoantigen, suggesting that it is not involved in the pathogenesis of BCR.
CLINICAL IMMUNOLOGY
(2023)
Article
Biochemical Research Methods
K. Madunic, Y. M. C. A. Luijkx, O. A. Mayboroda, G. M. C. Janssen, P. A. van Veelen, K. Strijbis, T. Wennekes, G. S. M. Lageveen-Kammeijer, M. Wuhrer
Summary: This study identified specific mucin O-glycans that mark butyrate-induced epithelial differentiation of the intestinal cell line CaCo-2 using porous graphitized carbon nano-liquid chromatography with electrospray ionization tandem mass spectrometry. The results showed that the fully differentiated butyrate-stimulated cells have a higher expression of sialylated O-glycan structures, while fucosylation is downregulated during differentiation. These findings provide insights into the dynamic O-glycosylation patterns in the gut and their functional role in gut-microbiota homeostasis and dysbiosis.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Oncology
Miranda H. Meeuwsen, Anne K. Wouters, Tassilo L. A. Wachsmann, Renate S. Hagedoorn, Michel G. D. Kester, Dennis F. G. Remst, Dirk M. van der Steen, Arnoud H. de Ru, Els P. van Hees, Martijn Kremer, Marieke Griffioen, Peter A. van Veelen, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: Jchain is highly expressed in multiple myeloma (MM) and Jchain-derived peptides presented in HLA molecules may be suitable antigens for T-cell therapy of MM. Using immunopeptidomics, Jchain-derived epitopes presented by MM cells were identified, and Jchain-specific T-cell clones were isolated using pHLA tetramer technology. TCRs targeting Jchain-derived peptides presented in four common HLA alleles demonstrated potent preclinical anti-myeloma activity, encouraging further preclinical testing and ultimately clinical development.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Bert van de Kooij, Evert de Vries, Rogier W. Rooswinkel, George M. C. Janssen, Frederique K. Kok, Peter A. van Veelen, Jannie Borst
Summary: The majority of proteins in mammalian cells are modified by N-terminal acetylation, which can have both inhibitory and promoting effects on protein degradation. However, proteome-wide stability measurements did not find a consistent correlation between N-terminal acetylation and protein stability. By analyzing protein stability datasets, it was found that N-terminal acetylation positively correlates with protein stability for GFP, but this correlation does not apply to the entire proteome. Further experiments showed that N-terminal acetylation can affect protein stability through competition with N-terminal ubiquitination, as well as other mechanisms independent of ubiquitination status.
SCIENTIFIC REPORTS
(2023)
Article
Microbiology
Emmely E. E. Treffers, Ali Tas, Florine E. M. Scholte, Arnoud H. H. de Ru, Eric J. J. Snijder, Peter A. A. van Veelen, Martijn J. J. van Hemert
Summary: Chikungunya virus (CHIKV) is a reemerging alphavirus that has caused outbreaks in Africa, Asia, and the Americas. Infection with CHIKV induces phosphorylation of eukaryotic elongation factor 2 (eEF2), leading to a shut-off of host-cell translation. This shut-off is mediated by the enzymatic activity of the nsP2 NTPase domain, which increases cellular cAMP concentration and activates PKA and eEF2 kinases. These findings provide insights into how alphaviruses modulate host cell metabolism and shut-off cellular protein synthesis.
Article
Immunology
Rosa A. van Amerongen, Sander Tuit, Anne K. Wouters, Marian van de Meent, Sterre L. Siekman, Miranda H. Meeuwsen, Tassilo L. A. Wachsmann, Dennis F. G. Remst, Renate S. Hagedoorn, Dirk M. van der Steen, Arnoud H. de Ru, Els M. E. Verdegaal, Peter A. van Veelen, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: Recurrent disease is common in ovarian cancer patients. Adoptive T-cell therapies using T-cell receptors (TCRs) targeting tumor-associated antigens (TAAs) show promise in treating less-immunogenic 'cold' ovarian tumors. This study identified PRAME, CTCFL, and CLDN6 as strictly tumor-specific TAAs with high expression in ovarian cancer and low expression in healthy tissues. High-avidity T-cell clones recognizing peptides derived from these TAAs were isolated and showed potent antitumor reactivity in vitro and in vivo. These findings provide valuable candidates for the treatment of ovarian cancer and other PRAME or CTCFL expressing cancers.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Marije A. J. de Rooij, Dennis F. G. Remst, Dirk M. van der Steen, Anne K. Wouters, Renate S. Hagedoorn, Michel G. D. Kester, Miranda H. Meeuwsen, Tassilo L. A. Wachsmann, Arnoud H. de Ru, Peter A. van Veelen, Els M. E. Verdegaal, J. H. Frederik Falkenburg, Mirjam H. M. Heemskerk
Summary: In this study, high-affinity cancer-specific TCRs targeting different melanoma-associated antigens (MAGEs) were identified and tested for antitumor efficacy. The most potent TCRs were transferred into CD8+ T cells and showed efficient reactivity against various tumor types. Seven MAGE-specific TCRs were identified, expanding the pool of cancer patients eligible for TCR gene therapy.
MOLECULAR THERAPY-ONCOLYTICS
(2023)
Article
Chemistry, Analytical
Bart Claushuis, Robert A. Cordfunke, Arnoud H. de Ru, Annemarie Otte, Hans C. van Leeuwen, Oleg I. Klychnikov, Peter A. van Veelen, Jeroen Corver, Jan W. Drijfhout, Paul J. Hensbergen
Summary: Proteases are enzymes that hydrolyze peptide bonds and play a crucial role in various biological processes. We developed a method to study the cleavage specificity of a group of bacterial metalloproteases and discovered new peptide substrates. Additionally, we characterized a new metalloprotease with a distinct cleavage specificity from the other two studied proteases.
ANALYTICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Leoni Abendstein, Douwe J. Dijkstra, Rayman T. N. Tjokrodirijo, Peter A. van Veelen, Leendert A. Trouw, Paul J. Hensbergen, Thomas H. Sharp
Summary: The authors used cryoEM and MS techniques to investigate IgG3-mediated complement activation and provide the first structural insights into IgG3. IgG3 is distinct from other IgG subclasses due to its extended hinge, allotypic diversity, and enhanced effector functions. However, the lack of structural information has limited its use as an immunotherapeutic candidate.
NATURE COMMUNICATIONS
(2023)
Correction
Cell Biology
Birol Cabukusta, Ilana Berlin, Daphne M. van Elsland, Iris Forkink, Menno Spits, Anja W. M. de Jong, Jimmy J. L. L. Akkermans, Ruud H. M. Wijdeven, George M. C. Janssen, Peter A. van Veelen, Jacques Neefjes
Article
Multidisciplinary Sciences
Daniel Salas-Lloret, Nicolette S. Jansen, Easa Nagamalleswari, Coen van der Meulen, Ekaterina Gracheva, Arnoud H. de Ru, H. Anne Marie Otte, Peter A. van Veelen, Andrea Pichler, Joachim Goedhart, Alfred C. O. Vertegaal, Roman Gonzalez-Prieto
Summary: Ubiquitin and ubiquitin-like conjugation cascades involve E1, E2, and E3 enzymes, with E3s providing substrate specificity. Through mass spectrometry-based approaches, more than 6500 SUMO2/3 target proteins have been identified. Using SUMO-activated target traps (SATTs), the substrates for eight different SUMO E3s were systematically identified, revealing E3 substrate preference. Quantitative proteomics and the Polar SATTs web-based tool were developed to measure substrate specificity and browse the dataset interactively. Overall, the study uncovers the E3-to-target wiring of 1388 SUMO substrates for different SUMO E3 ligases.
