PLoS Biology最新文献_第5页

An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE. 细菌间半胱氨酸蛋白酶毒素通过靶向II型DNA拓扑异构酶GyrB和ParE抑制细胞生长。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-27 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003208

Pin-Yi Song, Chia-En Tsai, Yung-Chih Chen, Yu-Wen Huang, Po-Pang Chen, Tzu-Haw Wang, Chao-Yuan Hu, Po-Yin Chen, Chuan Ku, Kuo-Chiang Hsia, See-Yeun Ting

{"title":"An interbacterial cysteine protease toxin inhibits cell growth by targeting type II DNA topoisomerases GyrB and ParE.","authors":"Pin-Yi Song, Chia-En Tsai, Yung-Chih Chen, Yu-Wen Huang, Po-Pang Chen, Tzu-Haw Wang, Chao-Yuan Hu, Po-Yin Chen, Chuan Ku, Kuo-Chiang Hsia, See-Yeun Ting","doi":"10.1371/journal.pbio.3003208","DOIUrl":"10.1371/journal.pbio.3003208","url":null,"abstract":"Bacteria deploy a diverse arsenal of toxic effectors to antagonize competitors, profoundly influencing the composition of microbial communities. Previous studies have identified an interbacterial toxin predicted to exhibit proteolytic activity that is broadly distributed among gram-negative bacteria. However, the precise mechanism of intoxication remains unresolved. Here, we demonstrate that one such protease toxin from Escherichia coli, Cpe1, disrupts DNA replication and chromosome segregation by cleaving conserved sequences within the ATPase domain of type II DNA topoisomerases GyrB and ParE. This cleavage effectively inhibits topoisomerase-mediated relaxation of supercoiled DNA, resulting in impaired bacterial growth. Cpe1 belongs to the papain-like cysteine protease family and is associated with toxin delivery pathways, including the type VI secretion system and contact-dependent growth inhibition. The structure of Cpe1 in complex with its immunity protein reveals a neutralization mechanism involving competitive substrate binding rather than active site occlusion, distinguishing it from previously characterized effector-immunity pairs. Our findings unveil a unique mode of interbacterial intoxication and provide insights into how bacteria protect themselves from self-poisoning by protease toxins.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003208"},"PeriodicalIF":9.8,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163103","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

An animal toxin-antidote system kills cells by creating a novel cation channel. 动物毒素解毒剂系统通过创造新的阳离子通道杀死细胞。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-27 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003182

Lews Caro, Aguan D Wei, Christopher A Thomas, Galen Posch, Ahmet Uremis, Michaela C Franzi, Sarah J Abell, Andrew H Laszlo, Jens H Gundlach, Jan-Marino Ramirez, Michael Ailion

引用次数: 0

Predictable motion is progressively extrapolated across temporally distinct processing stages in the human visual cortex. 可预测的运动是在人类视觉皮层的时间上不同的处理阶段逐步外推的。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-23 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003189

William Turner, Charlie Sexton, Philippa A Johnson, Ella M Wilson, Hinze Hogendoorn

{"title":"Predictable motion is progressively extrapolated across temporally distinct processing stages in the human visual cortex.","authors":"William Turner, Charlie Sexton, Philippa A Johnson, Ella M Wilson, Hinze Hogendoorn","doi":"10.1371/journal.pbio.3003189","DOIUrl":"10.1371/journal.pbio.3003189","url":null,"abstract":"Neural processing of sensory information takes time. Consequently, to estimate the current state of the world, the brain must rely on predictive processes-for example, extrapolating the motion of a ball to determine its probable present position. Some evidence implicates early (pre-cortical) processing in extrapolation, but it remains unclear whether extrapolation continues during later-stage (cortical) processing, where further delays accumulate. Moreover, the majority of such evidence relies on invasive neurophysiological techniques in animals, with accurate characterization of extrapolation effects in the human brain currently lacking. Here, we address these issues by demonstrating how precise probabilistic maps can be constructed from human EEG recordings. Participants (N = 18, two sessions) viewed a stimulus moving along a circular trajectory while electroencephalography (EEG) was recorded. Using linear discriminant analysis (LDA) classification, we extracted maps of stimulus location over time and found evidence of a forwards temporal shift occurring across temporally distinct processing stages. This accelerated emergence of position representations indicates extrapolation occurring at multiple stages of processing, with representations progressively shifted closer to real-time. We further show evidence of representational overshoot during early-stage processing following unexpected changes to an object's trajectory, and demonstrate that the observed dynamics can emerge without supervision in a simulated neural network via spike-timing-dependent plasticity.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003189"},"PeriodicalIF":9.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12133177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133352","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

Landscape of essential growth and fluconazole-resistance genes in the human fungal pathogen Cryptococcus neoformans. 人类真菌病原体新型隐球菌的基本生长景观和氟康唑耐药基因。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-22 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003184

R Blake Billmyre, Caroline J Craig, Joshua W Lyon, Claire Reichardt, Amy M Kuhn, Michael T Eickbush, Sarah E Zanders

{"title":"Landscape of essential growth and fluconazole-resistance genes in the human fungal pathogen Cryptococcus neoformans.","authors":"R Blake Billmyre, Caroline J Craig, Joshua W Lyon, Claire Reichardt, Amy M Kuhn, Michael T Eickbush, Sarah E Zanders","doi":"10.1371/journal.pbio.3003184","DOIUrl":"10.1371/journal.pbio.3003184","url":null,"abstract":"Fungi can cause devastating invasive infections, typically in immunocompromised patients. Treatment is complicated both by the evolutionary similarity between humans and fungi and by the frequent emergence of drug resistance. Studies in fungal pathogens have long been slowed by a lack of high-throughput tools and community resources that are common in model organisms. Here we demonstrate a high-throughput transposon mutagenesis and sequencing (TN-seq) system in Cryptococcus neoformans that enables genome-wide determination of gene essentiality. We employed a random forest machine learning approach to classify the C. neoformans genome as essential or nonessential, predicting 1,465 essential genes, including 302 that lack human orthologs. These genes are ideal targets for new antifungal drug development. TN-seq also enables genome-wide measurement of the fitness contribution of genes to phenotypes of interest. As proof of principle, we demonstrate the genome-wide contribution of genes to growth in fluconazole, a clinically used antifungal. We show a novel role for the well-studied RIM101 pathway in fluconazole susceptibility. We also show that insertions of transposons into the 5' upstream region can drive sensitization of essential genes, enabling screenlike assays of both essential and nonessential components of the genome. Using this approach, we demonstrate a role for mitochondrial function in fluconazole sensitivity, such that tuning down many essential mitochondrial genes via 5' insertions can drive resistance to fluconazole. Our assay system will be valuable in future studies of C. neoformans, particularly in examining the consequences of genotypic diversity.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003184"},"PeriodicalIF":9.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128971","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

Horizontal gene transfer of molecular weapons can reshape bacterial competition. 分子武器的水平基因转移可以重塑细菌竞争。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-21 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003095

Elisa T Granato, Jacob D Palmer, Christian Kirk, Connor Sharp, George Shillcock, Kevin R Foster

{"title":"Horizontal gene transfer of molecular weapons can reshape bacterial competition.","authors":"Elisa T Granato, Jacob D Palmer, Christian Kirk, Connor Sharp, George Shillcock, Kevin R Foster","doi":"10.1371/journal.pbio.3003095","DOIUrl":"10.1371/journal.pbio.3003095","url":null,"abstract":"Bacteria commonly use molecular weaponry to kill or inhibit competitors. Genes encoding many weapons and their associated immunity mechanisms can be transmitted horizontally. These transfer events are striking because they appear to undermine bacterial weapons when given to competing strains. Here, we develop an ecological model of bacterial warfare to understand the impacts of horizontal gene transfer. Our model predicts that weapon gene transfer from an attacker to a target strain is possible, but will typically occur at a low rate such that transfer has a negligible impact on competition outcomes. We tested the model empirically using a transmissible plasmid encoding colicin E2, a potent antibacterial toxin produced by Escherichia coli. As predicted by the model, we find that toxin plasmid transfer is feasible during warfare, but the resulting transconjugants remain rare. However, exploring the model further reveals realistic conditions where transfer is predicted to have major impacts. Specifically, the model predicts that whenever competing strains have access to unique nutrients, transconjugants can proliferate and reach high abundances. In support of these predictions, short- and long-term experiments show that transconjugants can thrive when nutrient competition is relaxed. Our work shows how horizontal gene transfer can reshape bacterial warfare in a way that benefits a weapon gene and strains that receive it. Interestingly, we also find that there is little cost to a strain that transfers a weapon gene, which is expected to further enable the horizontal gene transfer of molecular weapons.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003095"},"PeriodicalIF":9.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094771/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120700","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

Inhibition of the nucleolar RNA exosome facilitates adaptation to starvation. 抑制核仁RNA外泌体有助于适应饥饿。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-21 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003190

Xi Feng, Xiaoman Wang, Shouhong Guang, Shanshan Pang, Haiqing Tang

{"title":"Inhibition of the nucleolar RNA exosome facilitates adaptation to starvation.","authors":"Xi Feng, Xiaoman Wang, Shouhong Guang, Shanshan Pang, Haiqing Tang","doi":"10.1371/journal.pbio.3003190","DOIUrl":"10.1371/journal.pbio.3003190","url":null,"abstract":"In response to nutrient scarcity, cells must reallocate their limited energy for cellular maintenance at the expense of certain processes. How such a tradeoff is achieved remains largely unknown. RNA surveillance is crucial for the integrity of the transcriptome, whose defects are associated with several human diseases. Unexpectedly, we discover that the nucleolar RNA exosome, a key RNA surveillance machine, is inhibited by starvation. This is not merely the cessation of a temporarily non-essential process, but rather a key signal to allocate energy. By rewiring one-carbon metabolism, the inhibition of RNA exosome reduces translation, the most energy-consuming process. Energy is then conserved for fat synthesis to enhance cellular maintenance and starvation survival. Notably, while benefiting starvation fitness, RNA exosome inhibition impairs the life span of well-fed animals, indicating a tradeoff between short-term and long-term fitness. Our findings suggest that the nucleolar RNA surveillance can be temporarily sacrificed to facilitate starvation adaptation.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003190"},"PeriodicalIF":9.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12136472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144120800","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

Correction: Genome size influences plant growth and biodiversity responses to nutrient fertilization in diverse grassland communities. 更正：基因组大小影响不同草地群落植物生长和生物多样性对养分施肥的响应。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-20 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003195

Joseph A Morton, Carlos Alberto Arnillas, Lori Biedermann, Elizabeth T Borer, Lars A Brudvig, Yvonne M Buckley, Marc W Cadotte, Kendi Davies, Ian Donohue, Anne Ebeling, Nico Eisenhauer, Catalina Estrada, Sylvia Haider, Yann Hautier, Anke Jentsch, Holly Martinson, Rebecca L McCulley, Xavier Raynaud, Christiane Roscher, Eric W Seabloom, Carly J Stevens, Katerina Vesela, Alison Wallace, Ilia J Leitch, Andrew R Leitch, Erika I Hersch-Green

引用次数: 0

Accredited ocean sanctuaries for transforming captive cetacean care. 认可的海洋保护区，以改变圈养鲸类的护理。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-20 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003166

Lori Marino, Charles Vinick, Katy Foster, Jeff Foster, Rob Hicks, Graham McGrath, John Racanelli, Janesse Brewer

引用次数: 0

Excitatory projections from the nucleus reuniens to the medial prefrontal cortex modulate pain and depression-like behaviors in mice. 从团聚核到内侧前额皮质的兴奋性投射调节小鼠的疼痛和抑郁样行为。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-20 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003170

Shu-Ting Bao, Fang Rao, Cui Yin, Yong Niu, Jun-Li Cao, Cheng Xiao, Chunyi Zhou

{"title":"Excitatory projections from the nucleus reuniens to the medial prefrontal cortex modulate pain and depression-like behaviors in mice.","authors":"Shu-Ting Bao, Fang Rao, Cui Yin, Yong Niu, Jun-Li Cao, Cheng Xiao, Chunyi Zhou","doi":"10.1371/journal.pbio.3003170","DOIUrl":"10.1371/journal.pbio.3003170","url":null,"abstract":"The medial prefrontal cortex (mPFC) is implicated in emotional processing, cognition, and pain sensation, moreover, its circuitry undergoes neuroplastic changes in chronic pain. Although the nucleus reuniens (RE) of the thalamus provides significant glutamatergic inputs to the mPFC, it remains unclear whether this projection contributes to plasticity changes in the mPFC and pain-related behaviors in chronic pain. Using fiber photometry, we demonstrated that RE neurons responded to pain stimulation and emotional changes. Optogenetic activation of RE neurons and their projections to the mPFC (RE-mPFC projection) elicits hyperalgesia and depression-like behaviors in naïve mice. In a neuropathic pain mouse model, RE neurons were hyperactive, and the RE-mPFC projection was enhanced with a marked preference for the part innervating GABAergic circuits in the mPFC to that controlling mPFC neurons projecting to the ventrolateral periaqueductal gray (vlPAG). Expectedly, optogenetic inhibition of RE neurons and the RE-mPFC projection ameliorated pain-like and depression-like behaviors in neuropathic pain mice. Additionally, chemogenetic inhibition of RE-mPFC neurons conferred analgesia in neuropathic pain mice exposed to both acute and chronic morphine. Our findings highlight the significant role of the RE-mPFC pathway in neuropathic pain comorbid with depression, suggesting its potential as a target for treatment of neuropathic pain.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003170"},"PeriodicalIF":9.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112352","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

Permeability selection of biologically relevant membranes matches the stereochemistry of life on Earth. 生物相关膜的渗透性选择与地球上生命的立体化学相匹配。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2025-05-20 eCollection Date: 2025-05-01 DOI: 10.1371/journal.pbio.3003155

Olivia Goode, Urszula Łapińska, Juliano Morimoto, Georgina Glover, David S Milner, Alyson E Santoro, Stefano Pagliara, Thomas A Richards

{"title":"Permeability selection of biologically relevant membranes matches the stereochemistry of life on Earth.","authors":"Olivia Goode, Urszula Łapińska, Juliano Morimoto, Georgina Glover, David S Milner, Alyson E Santoro, Stefano Pagliara, Thomas A Richards","doi":"10.1371/journal.pbio.3003155","DOIUrl":"10.1371/journal.pbio.3003155","url":null,"abstract":"Early in the evolution of life, a proto-metabolic network was encapsulated within a membrane compartment. The permeability characteristics of the membrane determined several key functions of this network by determining which compounds could enter the compartment and which compounds could not. One key feature of known life is the utilization of right-handed d-ribose and d-deoxyribose sugars and left-handed l-amino acid stereochemical isomers (enantiomers); however, it is not clear why life adopted this specific chirality. Generally, archaea have l-phospholipid membrane chemistries and bacteria and eukaryotes have d-phospholipid membrane chemistries. We previously demonstrated that an l-archaeal and a d-intermediate membrane mimic, bearing a mixture of bacterial and archaeal lipid characteristics (a 'hybrid' membrane), displayed increased permeability for several key compounds compared to bacterial-like membranes. Here, we investigate if these membranes can drive stereochemical selection on pentose sugars, hexose sugars, and amino acids. Using permeability assays of homogenous unilamellar vesicles, we demonstrate that both membranes select for d-ribose and d-deoxyribose sugars while the hybrid membrane uniquely selects for a reduced alphabet of l-amino acids. This repertoire includes alanine, the plausible first l-amino acid utilized. We conclude such compartments could provide stereochemical compound selection matching those used by the core metabolism of life.","PeriodicalId":49001,"journal":{"name":"PLoS Biology","volume":"23 5","pages":"e3003155"},"PeriodicalIF":9.8,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112498","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