PLoS Biology最新文献_第6页

Pathogen subversion of neuro-epidermal signaling impairs lysosomal function to disrupt collagen homeostasis in Caenorhabditis elegans. 在秀丽隐杆线虫中，病原体颠覆神经表皮信号损害溶酶体功能以破坏胶原稳态。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2026-09-22 eCollection Date: 2026-09-01 DOI: 10.1371/journal.pbio.3004016

Qian Li, Yating Liu, Hanyi Chen, Weilie Xiao, Bin Qi

{"title":"Pathogen subversion of neuro-epidermal signaling impairs lysosomal function to disrupt collagen homeostasis in Caenorhabditis elegans.","authors":"Qian Li, Yating Liu, Hanyi Chen, Weilie Xiao, Bin Qi","doi":"10.1371/journal.pbio.3004016","DOIUrl":"10.1371/journal.pbio.3004016","url":null,"abstract":"The epidermis relies on collagen-rich extracellular matrices (ECMs) to maintain barrier integrity against pathogens. Lysosomes regulate cuticle collagen turnover, yet how neuronal signaling modulates epidermal lysosomal function and collagen organization during infection remains unclear. Using Pseudomonas aeruginosa PA14-Caenorhabditis elegans infection model, we demonstrate that pathogen-induced neuronal signaling disrupts epidermal lysosomal activity and collagen remodeling. PA14 infection triggers neurons to secrete NSIF-1 (Neuronal Secreted Immune Factor 1), which translocates to the epidermis and impairs lysosomal acidification, maturation, and degradation by suppressing the transcription factor ELT-3. This disruption leads to disorganized collagen structure, compromising cuticle integrity and host resistance. Genetic mutation of nsif-1 restores lysosomal function, enhances collagen density, and improves survival, while neuron-specific nsif-1 knockdown confirms its neuronal origin. Moreover, NSIF-1 inhibits ELT-3 nuclear localization, blocking its role in lysosomal-dependent ECM repair. Our study reveals a neuro-epidermal axis wherein pathogens exploit neuronal signals to disrupt lysosomal function and collagen homeostasis, identifying NSIF-1 and ELT-3 as potential targets to counteract infection-driven ECM dysregulation.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3004016"},"PeriodicalIF":7.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649122/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Antibodies targeting phage fiber and nozzle proteins impair Acinetobacter baumannii phage therapy by blocking infection and promoting immune clearance. 针对噬菌体纤维和喷嘴蛋白的抗体通过阻断感染和促进免疫清除来损害鲍曼不动杆菌噬菌体治疗。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2026-09-22 eCollection Date: 2026-09-01 DOI: 10.1371/journal.pbio.3004009

Heng Xue, Xinfeng Li, Guibo Rao, Fen Hu, Mingyue Zhong, Paulina Miernikiewicz, Rui Qiu, Sheng Cao, Krystyna Dąbrowska, Hang Yang

{"title":"Antibodies targeting phage fiber and nozzle proteins impair Acinetobacter baumannii phage therapy by blocking infection and promoting immune clearance.","authors":"Heng Xue, Xinfeng Li, Guibo Rao, Fen Hu, Mingyue Zhong, Paulina Miernikiewicz, Rui Qiu, Sheng Cao, Krystyna Dąbrowska, Hang Yang","doi":"10.1371/journal.pbio.3004009","DOIUrl":"10.1371/journal.pbio.3004009","url":null,"abstract":"Phage therapy represents a promising strategy to tackle the growing threat of antimicrobial resistance. Increasing evidence has demonstrated that phage-specific antibodies may compromise the efficacy of phage therapy. Nevertheless, little is known about how phage protein specificity of antibodies modulates phage therapeutic outcomes. Herein, we utilized AbP20, a podovirus against Acinetobacter baumannii, to explore the effects of antibodies elicited by each structural protein on phage therapy efficacy in a mouse infection model. Intraperitoneal administration of AbP20 once a day for 7 consecutive days induced robust phage-specific antibody responses that impaired phage therapy. Genome-guided antigen screening identified that antibodies elicited by the nozzle and fiber proteins of AbP20, rather than those targeting the portal, capsid, or adaptor proteins, are the dominant drivers of phage therapy failure. Specifically, fiber-specific and nozzle-specific antibodies block bacterial adsorption and genomic injection of AbP20, respectively. Meanwhile, both antibody subsets efficiently induce large phage aggregates and potentiate macrophage phagocytosis via an Fc receptor-independent pathway. An evolved AbP20 variant with improved neutralization escape capacity exhibited comparable antibody-accelerated phagocytosis and host immune clearance, yet partially rescued therapeutic failure caused by neutralizing antibodies. Collectively, this study elucidates that nozzle- and fiber-elicited neutralizing antibodies impair phage therapy via dual synergistic mechanisms, which offers novel insights into the multifaceted modulation of phage-specific antibodies against phage therapeutic efficacy.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3004009"},"PeriodicalIF":7.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Coordinated P450-UGT detoxification contributes to furanocoumarin tolerance associated with host plant range divergence in Helicoverpa. 协调的P450-UGT解毒有助于与寄主植物范围分化相关的呋喃香豆素耐受性。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2026-09-22 eCollection Date: 2026-09-01 DOI: 10.1371/journal.pbio.3004013

Huidong Wang, Yajie Kong, Xinyue Su, Yu Shi, Jianpeng Zhang, Yinjia Wang, Yajuan Xiao, Xing Geng, Jing Song, Yueru Ye, Kairan Zuo, Chris Bass, Shutang Zhou

{"title":"Coordinated P450-UGT detoxification contributes to furanocoumarin tolerance associated with host plant range divergence in Helicoverpa.","authors":"Huidong Wang, Yajie Kong, Xinyue Su, Yu Shi, Jianpeng Zhang, Yinjia Wang, Yajuan Xiao, Xing Geng, Jing Song, Yueru Ye, Kairan Zuo, Chris Bass, Shutang Zhou","doi":"10.1371/journal.pbio.3004013","DOIUrl":"10.1371/journal.pbio.3004013","url":null,"abstract":"Plants and herbivorous insects are engaged in a continuous evolutionary arms race driven by chemical defences and counter-defences. How insects integrate distinct detoxification systems to overcome diverse phytochemicals, and how such mechanisms contribute to host-range divergence, remains poorly understood. Here, we uncover a cooperative cytochrome P450-UDP-glycosyltransferase (UGT) cascade that mediates furanocoumarin tolerance in Helicoverpa armigera. Comparative genomic analyses across Helicoverpa and related noctuid species revealed that the UGT33 family is the most extensively expanded and dynamically diversified UGT lineage in Helicoverpa. Targeted CRISPR-Cas9 knockouts of UGT33 gene clusters in polyphagous H. armigera demonstrated their essential roles in detoxifying the furanocoumarins xanthotoxin and imperatorin. Combined metabolic and functional assays further established a sequential detoxification pathway, in which the cytochrome P450 CYP6AE19 catalyses either the O-dealkylation of xanthotoxin to yield xanthotoxol or the aromatic-carbon hydroxylation of xanthotoxin to form 5-hydroxyxanthotoxin, which are subsequently glycosylated by UGT33 enzymes to form their less-toxic glucosides. In contrast, impaired CYP6AE19-UGT33 coordination in the oligophagous Helicoverpa assulta was associated with reduced xanthotoxin detoxification and high sensitivity to this compound. Together, these findings provide direct evidence for coordinated Phase I-Phase II detoxification of a plant defensive compound in insects and show that functional divergence in this pathway contributes to interspecific differences in plant toxin tolerance, which are associated with contrasting dietary breadth in closely related herbivorous insects.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3004013"},"PeriodicalIF":7.2,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149026383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Who Eats Whom? A global food web derived from citizen science. 谁吃谁？一个来自公民科学的全球食物网。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2026-09-22 eCollection Date: 2026-09-01 DOI: 10.1371/journal.pbio.3003988

Bradley C Allf, Aditi Mallavarapu, David W Kikuchi, Nikhil Vasudeva, Robert R Dunn

引用次数: 0

Monovalent cations differentially regulate the activity of eukaryotic fluoride channels and impact fluoride resistance. 一价阳离子对真核生物氟离子通道活性的差异调控和对氟离子抗性的影响。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2026-09-21 eCollection Date: 2026-09-01 DOI: 10.1371/journal.pbio.3004008

Chia-Yu Kang, Sahar Heidari, Sabrina Kolb, Minjun An, Melanie D Ohi, Hedieh Torabifard, Randy B Stockbridge

{"title":"Monovalent cations differentially regulate the activity of eukaryotic fluoride channels and impact fluoride resistance.","authors":"Chia-Yu Kang, Sahar Heidari, Sabrina Kolb, Minjun An, Melanie D Ohi, Hedieh Torabifard, Randy B Stockbridge","doi":"10.1371/journal.pbio.3004008","DOIUrl":"10.1371/journal.pbio.3004008","url":null,"abstract":"Fluoride is an environmentally prevalent inhibitor of fungi, plants, and other eukaryotes. The fluoride exporter (FEX) is the major resistance mechanism that prevents intracellular fluoride accumulation in eukaryotes. FEX activity is sodium-dependent, but the mechanism for Na+ activation and the impact of other cations on FEX function remain poorly understood. Here, we show that sodium and lithium have different effects on channel activity. We leverage these differences to understand how monovalent cations regulate FEX. Functional assays in a reconstituted system show that lithium acts as a competitive antagonist of channel activation by competing with sodium for the central cation binding site. We further demonstrate that lithium markedly reduces fluoride tolerance of yeast. A cryo-EM structure of Candida albicans FEX with Li+, together with molecular dynamics (MD) simulations, reveals that differences in the preferred coordination sphere underlie the cation dependence of FEX activity. Whereas sodium binding supports a dynamic structure with a broader pore radius, lithium coordination favors a more rigid conformation that is more compact in the channel's vestibule. These changes perturb the tilt angle of a pore lining helix, and alter the rotamer of a key phenylalanine in the pore, which together constrict the permeation pathway. In addition to providing general insight into the mechanism of fluoride channel regulation by monovalent cations, these results identify lithium as a previously unknown environmental antagonist of eukaryotic fluoride export and tie cellular fluoride stress tolerance to the abundance of additional ions in the cellular milieu.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3004008"},"PeriodicalIF":7.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Myelin sheath lengths in the central nervous system scale to axon diameter via oligodendroglial Piezo1. 中枢神经系统髓鞘长度通过少突胶质Piezo1与轴突直径成比例。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2026-09-21 eCollection Date: 2026-09-01 DOI: 10.1371/journal.pbio.3003992

Amanda R Young, Ashley Galfano, Jacob Reyngoudt, Ryan W Lewis, Martha Cash, Beckam Polis, Myah Zalusky, Avipsha Datta, Marie E Bechler

{"title":"Myelin sheath lengths in the central nervous system scale to axon diameter via oligodendroglial Piezo1.","authors":"Amanda R Young, Ashley Galfano, Jacob Reyngoudt, Ryan W Lewis, Martha Cash, Beckam Polis, Myah Zalusky, Avipsha Datta, Marie E Bechler","doi":"10.1371/journal.pbio.3003992","DOIUrl":"10.1371/journal.pbio.3003992","url":null,"abstract":"Myelin sheath lengths vary by an order of magnitude in the central nervous system (CNS) and tune the timing of neuronal signaling. Thus, variation in myelin sheath length has been proposed to coordinate the timing of neuronal signaling to ultimately impact behavior. The mechanisms to establish myelin sheath length are unknown. For decades, reports have documented that in vivo myelin sheath size scales with the diameter of the ensheathed axon. We previously demonstrated diameter is sufficient to instruct myelin sheath lengths formed by rat oligodendrocytes using a synthetic axon culture system. The mechanisms of oligodendrocyte diameter-sensing and its translation into sheath elongation are still unknown. Here, we demonstrate that diameter-sensing and sheath length is locally regulated: each individual myelin sheath responds to the underlying fiber diameter. We uncover a novel mechanism for scaling myelin sheath length to fiber diameter, through mechanosensitive ion channel Piezo1. In mice in vivo, Piezo1 impacts the elongation of myelin sheaths on large diameter axons, recapitulating our in vitro results. Yet, surprisingly, there is no impact on myelin thickness with conditional Piezo1 loss. We propose Piezo1 provides a mechanism to establish hard-wired myelin sheath patterns, where oligodendrocytes transduce axon diameter into generating myelin segments with vastly different lengths.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003992"},"PeriodicalIF":7.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The nematode Caenorhabditis elegans has a cationic amphiphilic drug (CAD) defense system. 秀丽隐杆线虫具有阳离子两亲性药物（CAD）防御系统。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2026-09-21 eCollection Date: 2026-09-01 DOI: 10.1371/journal.pbio.3004006

Levon Tokmakjian, Duhyun Han, Kateryna Sihuta, Aanchal Aggarwal, Somayeh Pirhadi, Yao Wang, Andrew R Burns, Brittany Cooke, Siyue Ren, Marios Gavrielatos, Jiabao Liu, Henry M Krause, Carolyn L Cummins, Justin Nodwell, David R Koes, Peter J Roy

{"title":"The nematode Caenorhabditis elegans has a cationic amphiphilic drug (CAD) defense system.","authors":"Levon Tokmakjian, Duhyun Han, Kateryna Sihuta, Aanchal Aggarwal, Somayeh Pirhadi, Yao Wang, Andrew R Burns, Brittany Cooke, Siyue Ren, Marios Gavrielatos, Jiabao Liu, Henry M Krause, Carolyn L Cummins, Justin Nodwell, David R Koes, Peter J Roy","doi":"10.1371/journal.pbio.3004006","DOIUrl":"10.1371/journal.pbio.3004006","url":null,"abstract":"Cationic Amphiphilic Drugs (CADs) severely disrupt lysosomal function, which leads to a cellular pathology in humans characterized by excess phospholipids called phospholipidosis. Through a forward genetic screen and mining of published datasets, we discovered that CADs induce the expression of the CYP-35B family of cytochrome P450s and the PGP-13 p-glycoprotein pump via the nuclear receptors NHR-70 and NHR-107 in the nematode C. elegans. A pgp-13 fluorescent reporter revealed hundreds of human drugs that up-regulate the CAD defense system in vivo. Chemoinformatic analyses indicate that the pgp-13 reporter may be useful in identifying CADs that have pathogenic potential in humans. Mutant analyses coupled to metabolomics and structural modeling show that the CYP-35Bs are necessary and sufficient for CAD metabolism, and that CYP-35B2 D311 is key in mediating electrostatic interactions with the positively charged CADs. We also show that CAD metabolites are effluxed via PGP-13 acting partially redundantly with PGP-14 and that an intact defense system is necessary to resist CAD-induced pathology. Finally, we demonstrate that bacteria that likely cohabitate with C. elegans in nature trigger the CAD defense system, providing a plausible explanation for why a pathway that protects against anthropogenic small molecules exists in nematodes.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3004006"},"PeriodicalIF":7.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13619054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

AlloPool is a deep learning framework that infers protein allostery from molecular dynamics simulations. AlloPool是一个深度学习框架，可以从分子动力学模拟中推断蛋白质变构。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2026-09-21 eCollection Date: 2026-09-01 DOI: 10.1371/journal.pbio.3004002

Matthieu Marfoglia, Miguel A Pedraza-Joya, Lucas Guirardel, Aisima Chatzi Souleiman, Patrick Barth

{"title":"AlloPool is a deep learning framework that infers protein allostery from molecular dynamics simulations.","authors":"Matthieu Marfoglia, Miguel A Pedraza-Joya, Lucas Guirardel, Aisima Chatzi Souleiman, Patrick Barth","doi":"10.1371/journal.pbio.3004002","DOIUrl":"10.1371/journal.pbio.3004002","url":null,"abstract":"Recent advances in artificial intelligence have transformed protein structure prediction and design. However, protein function is governed not only by static structures but also by the conformational dynamics that allow proteins to access distinct functional states. Predicting these dynamic transitions, central to many biological processes, remains challenging due to the scarcity of high-resolution experimental data, which limits the training of machine-learning models for dynamic and energetic property prediction. Here, we present AlloPool, a graph neural network (GNN)-based framework that interprets molecular dynamics simulations by iteratively pruning residue-residue interactions to uncover minimal, time-resolved interaction networks that govern protein conformational dynamics and structural responses to chemical or mechanical perturbations, collectively known as allostery. By integrating temporal attention with graph aggregation, AlloPool learns evolving interaction graphs from equilibrium and non-equilibrium molecular dynamics simulations, enabling accurate reconstruction of dynamic trajectories and the interaction networks that drive conformational transitions. Validated across diverse dynamic protein systems, including binding domains, mechanosensors, signaling receptors, and enzymes, AlloPool maps allosteric communication pathways, predicts the effects of ligand binding, mechanical forces, and mutations, discovers transient dynamic states and outperforms existing machine-learning approaches in dynamic trajectory reconstruction. This advance provides a general framework for interpreting protein dynamics with broad implications for drug discovery, synthetic biology, and protein engineering.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3004002"},"PeriodicalIF":7.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

MucD regulates alginate biosynthesis through the proteolytic control of AlgX and AlgK in Pseudomonas aeruginosa. MucD通过控制铜绿假单胞菌中AlgX和AlgK的蛋白水解来调节海藻酸盐的生物合成。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2026-09-21 eCollection Date: 2026-09-01 DOI: 10.1371/journal.pbio.3003985

Yujun Jiang, Xin-Fu Yan, Rya Ero, Chao Wang, Kanaga Sabapathy, Yong-Gui Gao

{"title":"MucD regulates alginate biosynthesis through the proteolytic control of AlgX and AlgK in Pseudomonas aeruginosa.","authors":"Yujun Jiang, Xin-Fu Yan, Rya Ero, Chao Wang, Kanaga Sabapathy, Yong-Gui Gao","doi":"10.1371/journal.pbio.3003985","DOIUrl":"10.1371/journal.pbio.3003985","url":null,"abstract":"Pseudomonas aeruginosa is an opportunistic human pathogen capable of infecting a wide range of tissues and organs. Its persistence during chronic infection is strongly associated with biofilm formation, which depends on extracellular polysaccharides such as alginate. The HtrA-like periplasmic serine protease MucD is a key regulator of bacterial virulence, stress response, and alginate production, yet its molecular mechanism has remained largely unclear. Here, we discovered the alginate acetylation and export proteins AlgX and AlgK as MucD substrates, and characterized their degradation by mass spectrometry and bioinformatic analysis. We further determined the cryo-EM structure of MucD bound to an AlgK-derived substrate peptide, offering atomic insights into MucD oligomerization assembly, substrate recognition, and specificity. Together with structure-guided mutagenesis and biochemical assays, our results revealed that MucD proteolytic activity is governed by an equilibrium between a resting 12-mer and an active trimer. Crucially, we demonstrate that MucD represses alginate biosynthesis post-translationally, in addition to its previously implicated role in transcriptional regulation. These findings define a distinct activation mechanism and regulatory function for MucD and provide new insight into bacterial HtrA-like serine proteases.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3003985"},"PeriodicalIF":7.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13608001/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Regeneration programs buffer genetic defects in animal development. 再生计划可以缓冲动物发育过程中的遗传缺陷。

IF 7.2 1区生物学

PLoS Biology Pub Date : 2026-09-21 eCollection Date: 2026-09-01 DOI: 10.1371/journal.pbio.3004011

Kazunori Ando, Sushant Bangru, John Welsby, John D Thompson, Kenneth D Poss

{"title":"Regeneration programs buffer genetic defects in animal development.","authors":"Kazunori Ando, Sushant Bangru, John Welsby, John D Thompson, Kenneth D Poss","doi":"10.1371/journal.pbio.3004011","DOIUrl":"10.1371/journal.pbio.3004011","url":null,"abstract":"Regeneration programs enable animals to restore damaged or lost tissues, and the range of stimuli for these programs is incompletely understood. Here, we used zebrafish, a vertebrate species with exceptional regenerative capacity, to identify chemically induced mutations that alter regeneration-associated gene activation. Transgenic zebrafish with a permissive promoter and EGFP cassette inserted in the vicinity of the pro-regenerative factor gene fgf20a were mutagenized, and larvae homozygous for ENU-induced mutations were assessed for disruptions in fgf20a-directed reporter gene expression following fin fold amputation. One line was identified with heritable, elevated fgf20a:EGFP presence in the absence of experimental injury, localized to regions of fin fold tissue undergoing degeneration. Whole-genome sequencing identified a mutation within exon 72 of the fraser syndrome 1 (fras1) gene, mutated in patients with inherited skin disease. fras1 mutant larvae spontaneously displayed broader signatures of regeneration, and zebrafish crispants for homologs of other genes mutated in human developmental diseases also displayed regeneration-associated gene expression in regions of dysmorphology. Tempering Fgf signaling by transgenic expression of a dominant-negative Fgf receptor in fras1 mutants exacerbated the disease phenotype. Our findings provide evidence that regeneration programs are harnessed in response to developmental defects caused by genetic mutations, potentially buffering deleterious phenotypes.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"24 9","pages":"e3004011"},"PeriodicalIF":7.2,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13630312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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