Biochimie最新文献

{"title":"Mechanisms of outer membrane vesicles in bacterial drug resistance: Insights and implications.","authors":"Xianyu Zhang, Wenbo Ding, Jianyu Yang, Linran Gao, Qianying Wang, Jingjing Wang, Yu Luo, Xin Yuan, Baoyu Sun, Jifei Yang, Yujiao Zhou, Liyuan Sun","doi":"10.1016/j.biochi.2025.07.024","DOIUrl":"https://doi.org/10.1016/j.biochi.2025.07.024","url":null,"abstract":"<p><p>The emergence of antibiotic resistance has rendered the treatment of bacterial infections exceedingly challenging, with diseases caused by resistant strains often resulting in significant morbidity and mortality. Consequently, it is crucial to investigate the mechanisms underlying antibiotic resistance. Outer membrane vesicles (OMVs) are nanoscale spheres characterized by a double membrane structure, released by Gram-negative bacteria (GNB). While the mechanisms governing OMV biogenesis remain under investigation, three models have been proposed. These vesicles have been implicated in enhancing bacterial survival during antibiotic treatment and contributing to the onset and development of drug resistance through various pathways. OMVs function as a secretion system, delivering cargo that mediates intercellular communication to neighboring cells, and their closed structure facilitates this molecular delivery. Vesicles released into the extracellular compartment can protect bacteria from antibiotic treatment by promoting horizontal gene transfer, inactivating or binding antibiotics, influencing biofilm formation, and mediating bacterial gene mutations, among other mechanisms. Many studies have demonstrated that OMVs play a critical role during antibiotic exposure. An in-depth understanding of the mechanisms of OMVs in the development of bacterial drug resistance could help develop more effective therapeutic strategies to prevent persistent bacterial infections. This review focuses on summarising the latest evidence on the involvement of OMVs in the development of drug resistance, to provide ideas for future studies.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in vivo antibacterial activity of TsAP-2 from Tityus stigmurus scorpion venom in multidrug-resistant strains and its NMR three-dimensional structure.","authors":"Alessandra Daniele-Silva, Janainna Xavier Fernandes, Adriana Marina E Silva Parente, Bruno Amorim-Carmo, Suedson de Carvalho Silva Rodrigues, Lucas Hilário Nogueira de Sousa, Elizabeth C G Dos Santos, Thaís G de Carvalho, Raimundo F Araújo Júnior, Raudiney Frankilin Vasconcelos Mendes, Rafael Matos Ximenes, Arnóbio A da Silva-Júnior, Luiz Alberto Lira Soares, Renata Mendonça Araújo, Matheus F Fernandes-Pedrosa","doi":"10.1016/j.biochi.2025.07.023","DOIUrl":"10.1016/j.biochi.2025.07.023","url":null,"abstract":"<p><p>Microbial infections are a public health problem that combined with the emergence of resistant microorganisms have boosted the search for new antibiotic agents. In this approach, the antibacterial and antibiofilm effects in vitro of TsAP-2 (peptide from the Tityus stigmurus scorpion venom) were evaluated. In addition, its antimicrobial action in the skin wound model infected with Staphylococcus aureus and Galleria mellonella larvae infected with a multidrug-resistant strain and the effect of the combination with conventional antibiotics in vitro were investigated. TsAP-2 demonstrated broad-spectrum antibacterial activity in vitro, with antibiofilm action against standard and multidrug-resistant strains during early biofilm formation. Furthermore, TsAP-2 exhibited additive and synergistic effects when combined with conventional antibiotics. TsAP-2 revealed antibacterial and healing activity in vivo, reducing wound area and necrosis, while promoting an increase in neovascularization and epithelialization. TsAP-2 decreased the number of resistant bacteria in infected larvae, increasing their survival rate. The structural conformation of the peptide was assessed using circular dichroism and its three-dimensional structure was determined through NMR spectroscopy. In zwitterionic vesicles, TsAP-2 revealed a random conformation and a predominant helical structure in the presence of anionic vesicles. The three-dimensional structure of TsAP-2 obtained by NMR analysis indicates a helical segment from the 7th to the 15th residue, with flexibility in the N and C-terminal peptide domains. Taken together, this approach indicates the ability of TsAP-2 to change its conformation when interacting with biomimetic medium, highlights its extensive pharmacological potential, being an attractive candidate for the exploration of new anti-infective drugs.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The extreme C-terminal region of the phage BFK20 gp41 helicase has a role in DNA binding, protein-ATP interactions and ATPase activity.","authors":"Nora Halgasova, Lucia Bocanova, Jacob A Bauer, Barbora Niku, Kristina Papayova, Gabriela Bukovska","doi":"10.1016/j.biochi.2025.07.022","DOIUrl":"10.1016/j.biochi.2025.07.022","url":null,"abstract":"<p><p>Replication protein gp41 from bacteriophage BFK20 is a 537 residue SF2 family helicase. The N-terminal two-thirds of the gp41 sequence is homologous to XPB/Ssl2-like helicases, but no clear homology to any known and characterized protein could be found for the C-terminal one-third. We prepared and studied the following gp41 mutant recombinant proteins: deletion mutant gp41L481, missing the last 56 C-terminal amino acids (482-537), and five point mutants, each substituting a single amino acid from this region with alanine (K516A, R518A, D520A, D521A and E522A). We tested the ATPase activities, DNA binding abilities, thermal stabilities and protein-ATP interactions of each isolated protein and compared them with wild-type-like protein gp41HN. The ATPase activity and DNA binding ability of gp41L481 were significantly lower than gp41HN. The K516A and R518A mutations resulted in an almost total loss of ATPase activity, while the D521A mutation produced a lesser loss. The K516A mutation also significantly reduced the DNA binding ability of the mutant protein. All point mutants were less stable than the wild-type protein to a greater or lesser extent, and ATP had a significant stabilizing effect on most tested proteins. We conclude that the amino-acids at the extreme C-terminus of gp41 are important for its ATPase activity, DNA binding ability and protein-ATP interactions. BFK20 gp41 is an example of a phage helicase whose accessory domain significantly affects its properties and it provides additional evidence for the importance of accessory domains for helicase function.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144710282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ribosome biogenesis is a therapeutic vulnerability in pediatric neuroblastoma.","authors":"Camille Jouines, Piero Lo Monaco, Angéline Gaucherot, Marie-Ambre Monet, Isabelle Iacono Di Cacito, Valentin Simioni, Déborah Monchiet, Jean-Jacques Diaz, Valérie Combaret, Virginie Marcel, Frédéric Catez","doi":"10.1016/j.biochi.2025.07.018","DOIUrl":"10.1016/j.biochi.2025.07.018","url":null,"abstract":"<p><p>Neuroblastoma is a heterogeneous malignant pediatric tumor, the prognosis of which depends on patient age and disease stage. Current treatment strategies rely on four key diagnostic criteria: age, histological stage, genomic profile, and MYCN gene status. The oncogenic activity of MYC depends on ribosome biogenesis, which is hyperactivated in cancer cells to support their high proliferative capacity, and which may thus represent a vulnerability in neuroblastoma and constitute a therapeutic target. Here, using the well-established IMR-32 cell line along with a previously established panel of patient-derived neuroblastoma cell lines with varying MYCN status, we show that RNA polymerase I inhibition following exposure to CX-5461 and BMH-21 suppressed cell proliferation at nanomolar concentrations and induced ribosomal stress, leading to the activation of apoptosis and the p21 pathway. Furthermore, analysis of expression of ribosome biogenesis factors using publicly available datasets and RT-qPCR data from an in-house neuroblastoma cohort, we identified FBL as a marker of poor prognosis in neuroblastoma. Consistently, FBL knockdown reduced neuroblastoma cell proliferation, supporting its relevance as a therapeutic target. In conclusion, our study reinforces the therapeutic potential of ribosome biogenesis inhibition in neuroblastoma and expands the list of potential targets to include rRNA maturation factors. These findings highlight the relevance of targeting ribosome biogenesis as a novel approach for neuroblastoma treatment.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetically modified NK cells equipped with a switchable CAR for the treatment of HER2-positive cancers.","authors":"Maria A Streltsova, Anna A Boyko, Nadezhda A Alekseeva, Galina M Proshkina, Elena I Shramova, Maria V Grechikhina, Marina A Shevchenko, Olga A Shustova, Aleksey I Popodko, Elena V Konovalova, Aleksey A Schulga, Alexander M Sapozhnikov, Sergey M Deyev, Elena I Kovalenko","doi":"10.1016/j.biochi.2025.07.021","DOIUrl":"10.1016/j.biochi.2025.07.021","url":null,"abstract":"<p><p>This study is focused on the development and characterization of NK-92 cells bearing a switchable chimeric antigen receptor (CAR) system for targeting HER2-positive breast cancers. The system employs a universal CAR framework based on the high-affinity interaction between barstar within the CAR (BsCAR) and barnase in the antigen-specific module. The barnase component was fused with an engineered ankyrin repeat protein (DARPin) specifically recognizing the HER2 tumor antigen. NK-92 cells were successfully modified to express BsCAR, while control mock-NK92 cells were generated with a variant of BsCAR incapable of surface expression. Flow cytometry analysis confirmed successful transduction and proper surface expression of the BsCAR construct. The cytotoxic potential of the modified cells was evaluated through multiple approaches, including degranulation activity measurements, target cell lysis assays, and three-dimensional spheroid models. In the presence of the HER2-specific targeting module (Da-9.29-Bn), BsCAR-NK92 cells demonstrated significant and specific cytotoxicity against HER2-positive tumor cells, particularly those with high HER2 expression (SKBR3, SKOV-Kat, BT-474). The specificity of the system was confirmed using MCF7 cells expressing low levels of HER2 as controls. In three-dimensional models, BsCAR-NK92 cells maintained their cytotoxic activity. These findings demonstrate the potential of BsCAR-NK92 cells as an \"off-the-shelf\" therapeutic approach for targeting HER2-positive cancers, offering a flexible platform that can be adapted to target different tumor antigens through the modular barnase-barstar system.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144700664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequence characteristics, expression pattern, ovarian maintenance function and action mechanism of SIRT1 in Chlamys farreri.","authors":"Yan Xing, Dongyan Luo, Xijuan Lei, Xiaoling Liu","doi":"10.1016/j.biochi.2025.07.020","DOIUrl":"10.1016/j.biochi.2025.07.020","url":null,"abstract":"<p><p>SIRT1 (silent mating type information regulation 2 homolog 1), a histone deacetylase in Sirtuin family, regulates ovarian development and aging in higher mammals, but its role in invertebrates remains unexplored. This study investigated SIRT1 in the scallop Chlamys farreri. Its 2382 bp CDS (coding sequence) encodes 793 amino acids with the NTERM activation motif, the catalytic activity center and the ESA domain. QRT-PCR revealed that SIRT1 expression level in gonads was significantly higher than that in other tissues. In ovary, SIRT1 expression was the highest at growing stage, in the testes, the gene was highly expressed at growing stage and mature stage, suggesting it was related to the oocyte development, spermatocyte development and the sperm maturation. Furthermore, injection experiment showed resveratrol (SIRT1 activator) up-regulated SIRT1' expression, then oocyte numbers were increased but oocytes' maturity were suppressed, while nicotinamide (SIRT1 inhibitor) down-regulated SIRT1' expression, then oocyte numbers were reduced but oocytes' maturity were accelerated, suggesting SIRT1 can promote the oocytes proliferation while delay the oocytes maturation to prevent ovarian aging. Yeast one-hybrid and electrophoretic mobility shift assay confirmed SIRT1 binds Chlamys farreri FOXL2 via two sequences (SIF1: +28-+35; SIF2: +53-+60). Dual-luciferase reporter system showed FOXL2 could up-regulate SIRT1. It was worth mentioning that FOXL2 expression was up-regulated when nicotinamide down-regulated SIRT1 expression in ovaries, indicating there was a positive and negative feedback regulation between SIRT1 and FOXL2 expression, we speculate that those two genes play a crucial role in the development and maintenance of Chlamys farreri ovarian function.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing antimicrobial peptides: Overcoming challenges in the era of bacterial resistance.","authors":"Ratchaneewan Aunpad, Thanit Thitirungreangchai","doi":"10.1016/j.biochi.2025.07.019","DOIUrl":"10.1016/j.biochi.2025.07.019","url":null,"abstract":"<p><p>Antimicrobial resistance (AMR) in bacteria poses a significant public health threat, necessitating the development of alternative treatments. Antimicrobial peptides (AMPs) have emerged as promising candidates to address this issue due to their potent antimicrobial activity and diverse functional properties, which provide distinct advantages over conventional antibiotics. However, the clinical application of AMPs has been hindered by several challenges, including instability in vivo, safety concerns, and varying efficacy in vivo. To overcome these limitations, innovative approaches to AMP design and modification, as well as advanced delivery systems, are being actively investigated. This article provides a comprehensive overview of the classification, structural characteristics, and mechanisms of action of AMPs. Recent advances in AMP design and modification are highlighted, with a focus on strategies aimed at enhancing their therapeutic potential. Additionally, the development of delivery systems and formulation strategies for AMPs is discussed, with an emphasis on improving bioavailability, targeted distribution, and effectiveness in combating drug-resistant bacterial infections.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144683806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrophobic cluster analysis at protein and proteome scales.","authors":"Isabelle Callebaut, Jean-Paul Mornon","doi":"10.1016/j.biochi.2025.07.013","DOIUrl":"10.1016/j.biochi.2025.07.013","url":null,"abstract":"<p><p>Hydrophobic Cluster Analysis (HCA) adds secondary structure information to the analysis of protein amino acid sequence. Focusing on the elementary building blocks of protein folds, this approach has proved to be a powerful tool for detecting distant (hidden) relationships between proteins. At a time when huge masses of data are now available, both in terms of protein sequences and models of three-dimensional structures, it still constitutes a relevant tool for analyzing structural features at the scale of whole proteomes, enabling, among other things, to characterize the continuum between disorder and order and to explore the characteristics of protein dark matter. The aim of this mini-review is to provide a brief overview of this approach, describing its principles and achievements, recent developments and future prospects.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into the evolution and regulation of hybrid internal-terminal exons from tropomyosin exon 9A in Xenopus laevis.","authors":"Agnès Méreau, Hubert Lerivray, Justine Viet, Serge Hardy, Luc Paillard, Yann Audic","doi":"10.1016/j.biochi.2025.07.009","DOIUrl":"10.1016/j.biochi.2025.07.009","url":null,"abstract":"<p><p>Hybrid internal-terminal exons function as either internal or terminal exons. Their evolutionary origins remain unclear. Here, we investigate the phylogenetic origin and regulation of a hybrid exon, 9A9', in the TPM1 gene encoding tropomyosin alpha-1. We demonstrate that exon 9A9' was originally terminal in non-vertebrate deuterostomes and switched to internal in vertebrates through the exonization of a downstream exon, 9B. While the terminal nature of exon 9A9' was lost in most vertebrates, it was conserved in amphibians and coelacanths where it behaves as a hybrid internal-terminal exon. Using Xenopus laevis as a model, we show that the preservation of terminal exon 9A9' in the tpm1 gene likely arose from evolutionary pressures to mitigate the developmental toxicity linked to exon 9B inclusion during neurulation. We identify two peculiarities of terminal exon 9A9': it lies downstream of an AG-independent intron, and its definition is supported by an intronic cis-regulatory element, the UTE, which enhances recognition of the weak cleavage-polyadenylation site. Our findings characterize the molecular mechanisms underlying the regulation of hybrid internal-terminal exons and reveal how evolutionary pressures can reactivate vestigial traits to resolve developmental challenges. This work broadens our understanding of alternative splicing evolution and its significance in vertebrate development.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary DHA limitation did not affect swimming and metabolic performance, but reduced growth in wild European sea bass.","authors":"Mickaël Péron, Philippe Soudant, Fabienne Le Grand, David Mazurais, Victor Simon, Christel Lefrançois, Marie Vagner","doi":"10.1016/j.biochi.2025.07.005","DOIUrl":"10.1016/j.biochi.2025.07.005","url":null,"abstract":"<p><p>Long-chain polyunsaturated fatty acids (LC PUFA), particularly docosahexaenoic acid (DHA), are essential for cell membrane structure and function, impacting overall fish performance. These molecules, produced primarily by phytoplankton, are transferred up the trophic chain; however, climate change is predicted to modify phytoplankton communities with a cascading effect on the global DHA production and thus availability for consumers such as fish. This study aimed to evaluate the effects of dietary DHA limitation on i) the fatty acid composition in fish tissues ii) somatic growth, swimming performance, and metabolic rates, and iii) the activation of biosynthetic pathways at the molecular level, by measuring gene expression involved in DHA synthesis. We conditioned wild-caught European sea bass (Dicentrarchus labrax) juveniles for five months on a DHA-depleted or control diet. Dietary DHA limitation led to selective retention or synthesis of DHA in fish tissues (liver, brain, and muscle), a reduced growth and an up-regulation of DHA biosynthetic pathways without compensating for DHA deficiency in tissues. Fish fed the low DHA diet may have up-regulated biosynthetic pathway which may be energetically costly, as high tissue DHA correlated with reduced growth. Alternatively, the lower tissue DHA levels in these fish might cause slower growth. However, metabolic rates and swimming performance were not affected by dietary treatment. Inter-individual variability was observed across all variables, highlighting underlying trade-offs when facing DHA limitation. This work provides insight into the physiological consequences of dietary DHA reduction due to global change and the mechanisms fish employ to mitigate its effects.</p>","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}