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Structural and functional analysis reveals the catalytic mechanism and substrate binding mode of the broad-spectrum endolysin Ply2741. 结构和功能分析揭示了广谱内溶菌酶 Ply2741 的催化机理和底物结合模式。
IF 5.5 1区 农林科学
Virulence Pub Date : 2025-12-01 Epub Date: 2025-01-14 DOI: 10.1080/21505594.2024.2449025
Shuang Wang, Xinxin Li, Jiahui Ma, Xiaochao Duan, Haiyan Wang, Linkang Wang, Dayue Hu, Wenwu Jiang, Xiangmin Li, Ping Qian
{"title":"Structural and functional analysis reveals the catalytic mechanism and substrate binding mode of the broad-spectrum endolysin Ply2741.","authors":"Shuang Wang, Xinxin Li, Jiahui Ma, Xiaochao Duan, Haiyan Wang, Linkang Wang, Dayue Hu, Wenwu Jiang, Xiangmin Li, Ping Qian","doi":"10.1080/21505594.2024.2449025","DOIUrl":"10.1080/21505594.2024.2449025","url":null,"abstract":"<p><p>The emergence of antibiotic-resistant bacteria has attracted interest in the field of endolysins. Here, we analyzed the diversity of <i>Streptococcus</i> endolysins and identified a new endolysin, Ply2741, that exhibited broad-spectrum bactericidal activity. Our results demonstrated that Ply2741 could effectively eradicate multidrug-resistant gram-positive pathogens <i>in vitro</i> and <i>in vivo</i>. Structural analysis revealed that the bactericidal activity of Ply2741 depends on the classic \"Cys-His-Asn\" catalytic triad. Site-directed mutagenesis results further identified that the conserved residue Gln29, located near the catalytic triad, also contributes to the lytic activity of Ply2741. Furthermore, the key residues (R189 and W250) in the Ply2741 cell wall binding domain (CBD) responsible for binding to peptidoglycan were revealed by molecular docking and fluorescence-activated cell sorting (FACS) analysis. Ply2741 demonstrates a broad lytic spectrum, with significant bactericidal activity against <i>Enterococcus</i>, <i>Staphylococcu</i>s, <i>and Streptococcus</i> and species. To the best of our knowledge, we found that residue Gln29 participated in the lytic activity of endolysin for the first time. Additionally, we systematically elucidate the binding mode and key residues of the Ply2741CBD. This study proposes Ply2741 as a potential antibiotic substitute and provides a structural basis for the modification and design of endolysins.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2449025"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Restriction of mitochondrial oxidation of glutamine or fatty acids enhances intracellular growth of Mycobacterium abscessus in macrophages. 限制线粒体氧化谷氨酰胺或脂肪酸可促进巨噬细胞内脓肿分枝杆菌的生长。
IF 5.5 1区 农林科学
Virulence Pub Date : 2025-12-01 Epub Date: 2025-01-19 DOI: 10.1080/21505594.2025.2454323
Ho Won Kim, Ji Won Lee, Hoe Sun Yoon, Hwan-Woo Park, Young Ik Lee, Sung Ki Lee, Jake Whang, Jong-Seok Kim
{"title":"Restriction of mitochondrial oxidation of glutamine or fatty acids enhances intracellular growth of <i>Mycobacterium abscessus</i> in macrophages.","authors":"Ho Won Kim, Ji Won Lee, Hoe Sun Yoon, Hwan-Woo Park, Young Ik Lee, Sung Ki Lee, Jake Whang, Jong-Seok Kim","doi":"10.1080/21505594.2025.2454323","DOIUrl":"10.1080/21505594.2025.2454323","url":null,"abstract":"<p><p><i>Mycobacterium abscessus</i> (Mab), a nontuberculous mycobacterium, is increasing in prevalence worldwide and causes treatment-refractory pulmonary diseases. However, how Mab rewires macrophage energy metabolism to facilitate its survival is poorly understood. We compared the metabolic profiles of murine bone marrow-derived macrophages (BMDMs) infected with smooth (S)- and rough (R)-type Mab using extracellular flux technology. Mab infection shifted BMDMs towards a more energetic phenotype, marked by increased oxidative phosphorylation (OXPHOS) and glycolysis, with a significantly greater enhancement in OXPHOS. This metabolic adaptation was characterized by enhanced ATP production rates, particularly in cells infected with S-type Mab, highlighting OXPHOS as a key energy source. Notably, Mab infection also modulated mitochondrial substrate preferences, increasing fatty acid oxidation capabilities while revealing significant changes in glutamine dependency and flexibility. R-type Mab infections exhibited a marked decrease in glutamine reliance but enhanced metabolic flexibility and capacity. Furthermore, targeting metabolic pathways related to glutamine and fatty acid oxidation exacerbated Mab growth within macrophages, suggesting these pathways play a protective role against infection. These insights advance our understanding of Mab's impact on host cell metabolism and propose a novel avenue for therapeutic intervention. By manipulating host mitochondrial metabolism, we identify a potential host-directed therapeutic strategy against Mab, offering a promising alternative to conventional treatments beleaguered by drug resistance. This study underscores the importance of exploring metabolic interventions to combat Mab infection, paving the way for innovative approaches in the fight against this formidable pathogen.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2454323"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11749347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143012744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Arginine depletion-induced autophagy and metabolic dysregulation are involved in the disease severity of hand, foot, and mouth disease. 精氨酸耗竭诱导的自噬和代谢失调与手足口病的严重程度有关。
IF 5.5 1区 农林科学
Virulence Pub Date : 2025-12-01 Epub Date: 2024-12-28 DOI: 10.1080/21505594.2024.2440541
Yuefei Jin, Wangquan Ji, Liang Zhang, Dejian Dang, Bingqing Yu, Xiaolong Zhang, Yuxiang Zhang, Jiaqi Li, Yaodong Zhang, Rongxin Yang, Haiyan Yang, Shuaiyin Chen, Fang Wang, Guangcai Duan
{"title":"Arginine depletion-induced autophagy and metabolic dysregulation are involved in the disease severity of hand, foot, and mouth disease.","authors":"Yuefei Jin, Wangquan Ji, Liang Zhang, Dejian Dang, Bingqing Yu, Xiaolong Zhang, Yuxiang Zhang, Jiaqi Li, Yaodong Zhang, Rongxin Yang, Haiyan Yang, Shuaiyin Chen, Fang Wang, Guangcai Duan","doi":"10.1080/21505594.2024.2440541","DOIUrl":"https://doi.org/10.1080/21505594.2024.2440541","url":null,"abstract":"<p><p>Amino acid metabolism provides significant insight into the development and prevention of many viral diseases. Therefore, the present study aimed to compare the amino acid profiles of hand, foot, and mouth disease (HFMD) patients with those of healthy individuals and to further reveal the molecular mechanisms of HFMD severity. Using UPLC-MS/MS, we determined the plasma amino acid expression profiles of pediatric patients with HFMD (mild, <i>n</i> = 42; severe, <i>n</i> = 43) and healthy controls (<i>n</i> = 25). Brain tissues from CVA6-infected mice were examined using untargeted metabolomics. Several amino acids were significantly different between the three groups. Pathway analysis revealed that arginine, proline, and tryptophan metabolism are implicated in the pathogenesis of HFMD. A similar arginine depletion was observed in the brain tissues of CVA6-infected mice. Importantly, L-arginine supplementation improved the survival rate of CVA6-infected mice, inhibited virus multiplication, and reduced pathological autophagy associated with mTOR-autophagy pathway in the brain. Collectively, arginine, as the hub amino acid metabolite of the mammalian target of rapamycin (mTOR) signaling pathway affecting autophagy, plays an important role in the pathogenesis of severe HFMD. L-arginine supplementation may serve as a potential therapeutic option for critical patients with HFMD.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2440541"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Optimizing encephalomyocarditis virus VP1 protein assembly on pseudorabies virus envelope via US9 protein anchoring. 利用US9蛋白锚定优化脑心肌炎病毒VP1蛋白在伪狂犬病毒包膜上的组装
IF 5.5 1区 农林科学
Virulence Pub Date : 2025-12-01 Epub Date: 2024-12-27 DOI: 10.1080/21505594.2024.2445235
Bao Ru Ren, Hui Qin, Yan Fang Zhang, Xuan Ying Du, Hao Chen Sun, Yang Luo, Yan Zi Gan, Jian Long Wang, Wei Hu, Sheng Bo Cao, Yang Yang
{"title":"Optimizing encephalomyocarditis virus VP1 protein assembly on pseudorabies virus envelope via US9 protein anchoring.","authors":"Bao Ru Ren, Hui Qin, Yan Fang Zhang, Xuan Ying Du, Hao Chen Sun, Yang Luo, Yan Zi Gan, Jian Long Wang, Wei Hu, Sheng Bo Cao, Yang Yang","doi":"10.1080/21505594.2024.2445235","DOIUrl":"https://doi.org/10.1080/21505594.2024.2445235","url":null,"abstract":"<p><p>Live herpesvirus-vectored vaccines are critical in veterinary medicine, but they can sometimes offer insufficient protection due to suboptimal antigen expression or localization. Encephalomyocarditis virus (EMCV) is a significant zoonotic threat, with VP1 protein as a key immunogen on its capsid. To enhance immunogenicity, we explored the use of recombinant pseudorabies virus (rPRV) as a vaccine vector against EMCV. In silico analysis indicated that fusing VP1 with US9 enhances the formation of a type II transmembrane heterodimer. We constructed six rPRV groups expressing different VP1 variants and found that VP1 fused with US9's C-terminal (US9-VP1) enhances VP1's membrane localization and its incorporation into the PRV envelope, unlike wild-type VP1. Immunogold electron microscopy illustrated that rPRV with deleted US8 and US9, supplemented with US8 regulatory sequence (rΔ89-U9VP1), improved VP1 incorporation into the viral envelope. Post-immunization, only rΔ89-U9VP1 provided 100% protection against EMCV in mice and induced high levels of virus-neutralizing antibodies in piglets. Additionally, rPRV expressing VP1 stimulated robust T-cell responses, as demonstrated by flow cytometry and ELISpot assays. This study introduces rPRV as a potential EMCV vaccine, demonstrating that the selection of the US9 C-terminal domain and US8 regulatory sequence significantly enhances the presentation of heterologous antigens, improving vaccine efficacy.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2445235"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142898494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Human SLAM-adapted canine distemper virus can enter human peripheral blood mononuclear cells and replicate in mice expressing human SLAM and defective for STAT1 expression.
IF 5.5 1区 农林科学
Virulence Pub Date : 2025-12-01 Epub Date: 2025-02-21 DOI: 10.1080/21505594.2025.2457967
Boyu Zhai, Wei Ran, Yiyang Sun, Angelita Alcos, Mengjia Liu, Jie Chen, Christopher D Richardson, Dongbo Sun, Jianjun Zhao
{"title":"Human SLAM-adapted canine distemper virus can enter human peripheral blood mononuclear cells and replicate in mice expressing human SLAM and defective for STAT1 expression.","authors":"Boyu Zhai, Wei Ran, Yiyang Sun, Angelita Alcos, Mengjia Liu, Jie Chen, Christopher D Richardson, Dongbo Sun, Jianjun Zhao","doi":"10.1080/21505594.2025.2457967","DOIUrl":"10.1080/21505594.2025.2457967","url":null,"abstract":"<p><p>Canine distemper virus (CDV) is a member of the genus <i>Morbillivirus</i> with a worldwide distribution that causes fatal diseases in canids and marine mammals. In recent years, CDV has demonstrated the remarkable ability of pathogens to cross species barriers. The natural host range of CDV has expanded from Canidae to Primates, presumably attributed to ecological shifts and the emergence of viral variants. Therefore, it is important to investigate whether CDV can infect humans by adapting to the human signalling lymphocyte activation molecule (hSLAM) receptor to cross the species barrier. Through successive passaging and plaque cloning of a CDV wild-type strain (5804PeH) in Vero cells expressing hSLAM (Vero-hSLAM), we obtained an hSLAM adaptive strain, 5804PeH-VhS. The adapted CDV strain exhibited a D540G mutation within the receptor-binding domain (RBD) of the haemagglutinin (H) protein. The H<sup>D540G</sup> mutation has enhanced cell-cell fusion activity in Vero-hSLAM cells. This adaptation allowed the CDV strain to infect human peripheral blood mononuclear cells (PBMCs), particularly T lymphocytes and inhibited lymphocyte proliferation. Additionally, this strain could replicate in the lymphoid tissues of transgenic mice that express the hSLAM receptor, causing viraemia. However, the adapted strain did not spread to the epithelial cells or the central nervous system of the mice. While this adaptation indicates a potential risk, there is no definitive evidence that the virus can spread among humans.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2457967"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11849921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Glucocorticoid receptor epigenetic activity in the heart.
IF 2.9 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-02-25 DOI: 10.1080/15592294.2025.2468113
Olukunle Akinborewa, Mattia Quattrocelli
{"title":"Glucocorticoid receptor epigenetic activity in the heart.","authors":"Olukunle Akinborewa, Mattia Quattrocelli","doi":"10.1080/15592294.2025.2468113","DOIUrl":"10.1080/15592294.2025.2468113","url":null,"abstract":"<p><p>The glucocorticoid receptor (GR) is a critical nuclear receptor that regulates gene expression in diverse tissues, including the heart, where it plays a key role in maintaining cardiovascular health. GR signaling influences essential processes within cardiomyocytes, including hypertrophy, calcium handling, and metabolic balance, all of which are vital for proper cardiac function. Dysregulation of GR activity has been implicated in various cardiovascular diseases (CVDs), highlighting the potential of GR as a therapeutic target. Remarkably, recent insights into GR's epigenetic regulation and its interaction with circadian rhythms reveal opportunities to optimize therapeutic strategies by aligning glucocorticoid administration with circadian timing. In this review, we provide an overview of the glucocorticoid receptor's role in cardiac physiology, detailing its genomic and non-genomic pathways, interactions with epigenetic and circadian regulatory mechanisms, and implications for cardiovascular disease. By dissecting these molecular interactions, this review outlines the potential of epigenetically informed and circadian-timed interventions that could change the current paradigms of CVD treatments in favor of precise and effective therapies.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2468113"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11866966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143499980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Germ granule-mediated mRNA storage and translational control.
IF 3.6 3区 生物学
RNA Biology Pub Date : 2025-12-01 Epub Date: 2025-02-06 DOI: 10.1080/15476286.2025.2462276
Hoang-Anh Pham-Bui, Mihye Lee
{"title":"Germ granule-mediated mRNA storage and translational control.","authors":"Hoang-Anh Pham-Bui, Mihye Lee","doi":"10.1080/15476286.2025.2462276","DOIUrl":"10.1080/15476286.2025.2462276","url":null,"abstract":"<p><p>Germ cells depend on specialized post-transcriptional regulation for proper development and function, much of which is mediated by dynamic RNA granules. These membrane-less organelles form through the condensation of RNA and proteins, governed by multivalent biomolecular interactions. RNA granules compartmentalize cellular components, selectively enriching specific factors and modulating biochemical reactions. Over recent decades, various types of RNA granules have been identified in germ cells across species, with extensive studies uncovering their molecular roles and developmental significance. This review explores the mRNA regulatory mechanisms mediated by RNA granules in germ cells. We discuss the distinct spatial organization of specific granule components and the variations in material states of germ granules, which contribute to the regulation of mRNA storage and translation. Additionally, we highlight emerging research on how changes in these material states, during developmental stages, reflect the dynamic nature of germ granules and their critical role in development.</p>","PeriodicalId":21351,"journal":{"name":"RNA Biology","volume":" ","pages":"1-11"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Honey-derived Paenibacillus spp. with potential to affect bee brood development in Apis mellifera: Are they a new threat to honey bees?
IF 5.5 1区 农林科学
Virulence Pub Date : 2025-12-01 Epub Date: 2025-02-15 DOI: 10.1080/21505594.2025.2451170
Keiko Nakamura, Mariko Okamoto, Takashi Mada, Mariko Harada, Kayo Okumura, Daisuke Takamatsu
{"title":"Honey-derived <i>Paenibacillus</i> spp. with potential to affect bee brood development in <i>Apis mellifera</i>: Are they a new threat to honey bees?","authors":"Keiko Nakamura, Mariko Okamoto, Takashi Mada, Mariko Harada, Kayo Okumura, Daisuke Takamatsu","doi":"10.1080/21505594.2025.2451170","DOIUrl":"10.1080/21505594.2025.2451170","url":null,"abstract":"<p><p>Honey bees are important pollinators in both agriculture and ecosystems, and their health is essential for sustainable human development. Although only two bacteria, <i>Paenibacillus larvae</i> and <i>Melissococcus plutonius</i>, have been identified as bacterial pathogens in honey bee brood for over 100 years, we found three additional <i>Paenibacillus</i> strains (<i>Paenibacillus</i> sp. J27TS7, <i>Paenibacillus azoreducens</i> J34TS1, and <i>Paenibacillus melissococcoides</i> J46TS7) in honey that harmed honey bee brood development. In particular, <i>Paenibacillus</i> sp. J27TS7 was highly virulent in bee larvae (the median lethal dose [LD<sub>50</sub>] = 12.7 spores/larva) and was comparable to <i>P. larvae</i> (LD<sub>50</sub> = 2.3-11.5 spores/larva). <i>Paenibacillus azoreducens</i> J34TS1 showed the second-highest virulence (LD<sub>50</sub> = 45.9 spores/larva), and <i>P. melissococcoides</i> J46TS7 was the least virulent (LD<sub>50</sub> = 469.0 spores/larva). However, <i>P. melissococcoides</i> was most frequently detected in Japanese honey among the three species, with the highest concentration being 1.8 × 10<sup>6</sup> spores/mL honey, suggesting its wide distribution in Japanese apiaries. The novel pathogenic <i>Paenibacillus</i> species were categorized into the fast killer (<i>Paenibacillus</i> sp. J27TS7), medium-fast killer (<i>P. melissococcoides</i>), and slow killer (<i>P. azoreducens</i>) like <i>P. larvae</i> strains in terms of the time to kill infected brood; however, histopathological and genome analyses indicated that their pathogenic mechanisms were different from those of <i>P. larvae</i> strains. Moreover, <i>P. melissococcoides</i> showed differences in virulence depending on the lineage of the strain. These findings represent the first discovery of honey bee brood pathogens in more than 100 years and indicate the need to look beyond known pathogens for a comprehensive understanding of honey bee diseases.</p>","PeriodicalId":23747,"journal":{"name":"Virulence","volume":"16 1","pages":"2451170"},"PeriodicalIF":5.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11834430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","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 novel mannan-specific chimeric antigen receptor M-CAR redirects T cells to interact with Candida spp. hyphae and Rhizopus oryzae spores.
IF 4.2 4区 生物学
Bioengineered Pub Date : 2025-12-01 Epub Date: 2025-02-01 DOI: 10.1080/21655979.2025.2458786
Júlia Garcia Guimarães, Gabriela Yamazaki de Campos, Michele Procópio Machado, Patrícia Kellen Martins Oliveira Brito, Thaila Fernanda Dos Reis, Gustavo Henrique Goldman, Patricia Vianna Bonini Palma, Thais Fernanda de Campos Fraga-Silva, Daniela Cardoso Umbelino Cavallin, James Venturini, Thiago Aparecido da Silva
{"title":"A novel mannan-specific chimeric antigen receptor M-CAR redirects T cells to interact with <i>Candida</i> spp. hyphae and <i>Rhizopus oryzae</i> spores.","authors":"Júlia Garcia Guimarães, Gabriela Yamazaki de Campos, Michele Procópio Machado, Patrícia Kellen Martins Oliveira Brito, Thaila Fernanda Dos Reis, Gustavo Henrique Goldman, Patricia Vianna Bonini Palma, Thais Fernanda de Campos Fraga-Silva, Daniela Cardoso Umbelino Cavallin, James Venturini, Thiago Aparecido da Silva","doi":"10.1080/21655979.2025.2458786","DOIUrl":"10.1080/21655979.2025.2458786","url":null,"abstract":"<p><p>Invasive fungal infections (IFIs) are responsible for elevated rates of morbidity and mortality, causing around of 1.5 million deaths annually worldwide. One of the main causative agents of IFIs is <i>Candida albicans</i>, and non-albicans <i>Candida</i> species have emerged as a spreading global public health concernment. Furthermore, COVID-19 has contributed to a boost in the incidence of IFIs, such as mucormycosis, in which <i>Rhizopus oryzae</i> is the most prevalent causative agent. The effector host immune response against IFIs depends on the activity of T cells, which are susceptible to the regulatory effects triggered by fungal virulence factors. The fungal cell wall plays a crucial role as a virulence factor, and its remodeling compromises the development of a specific T-cell response. The redirection of Jurkat T cells to target <i>Candida</i> spp. by recognizing targets expressed on the fungal cell wall can be facilitated using chimeric antigen receptor (CAR) technology. This study generated an M-CAR that contains an scFv with specificity to α-1,6 mannose backbone of fungal mannan, and the expression of M-CAR on the surface of modified Jurkat cells triggered a strong activation against <i>Candida albicans</i> (hyphae form), <i>Candida tropicalis</i> (hyphae form), <i>Candida parapsilosis</i> (pseudohyphal form), and <i>Candida glabrata</i> (yeast form). Moreover, M-CAR Jurkat cells recognized <i>Rhizopus oryzae</i> spores, which induced high expression of cell activation markers. Thus, a novel Mannan-specific CAR enabled strong signal transduction in modified Jurkat cells in the presence of <i>Candida</i> spp. or <i>R. oryzae</i>.</p>","PeriodicalId":8919,"journal":{"name":"Bioengineered","volume":"16 1","pages":"2458786"},"PeriodicalIF":4.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Adipose tissue and adipose-derived stromal cells can reduce skin contraction in an in vitro tissue engineered full thickness skin model.
IF 3.5 4区 生物学
Adipocyte Pub Date : 2025-12-01 Epub Date: 2025-03-19 DOI: 10.1080/21623945.2025.2473367
Victoria L Workman, Anna-Victoria Giblin, Nicola H Green, Sheila MacNeil, Vanessa Hearnden
{"title":"Adipose tissue and adipose-derived stromal cells can reduce skin contraction in an <i>in vitro</i> tissue engineered full thickness skin model.","authors":"Victoria L Workman, Anna-Victoria Giblin, Nicola H Green, Sheila MacNeil, Vanessa Hearnden","doi":"10.1080/21623945.2025.2473367","DOIUrl":"https://doi.org/10.1080/21623945.2025.2473367","url":null,"abstract":"<p><p>Skin contracts during wound healing to facilitate wound closure. In some patients, skin contraction can lead to the formation of skin contractures that limit movement, impair function, and significantly impact well-being. Current treatment options for skin contractures are burdensome for patients, and there is a high risk of recurrence. Autologous fat grafting can improve the structure and function of scarred skin; however, relatively little is known about the effect of fat on skin contraction. In this study, an in vitro tissue-engineered model of human skin was used to test the effects of adipose tissue and adipose-derived stromal cells on skin contraction. Untreated tissue-engineered skin contracted to approximately 60% of the original area over 14 days in culture. The addition of adipose tissue reduced this contraction by 50%. Adipose tissue, which was emulsified or concentrated and high doses of adipose-derived stromal cells (ADSC) were able to inhibit contraction to a similar degree; however, lower doses of ADSC did not show the same effect. In conclusion, the subcutaneous application of adipose tissue has the potential to inhibit skin contraction. This study provides in vitro evidence to support the use of autologous fat grafting to prevent skin contraction in patients most at risk.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"14 1","pages":"2473367"},"PeriodicalIF":3.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655606","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}
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