PLoS Pathogens最新文献_第3页

Transcriptome analysis of two isolates of the tomato pathogen Cladosporium fulvum, uncovers genome-wide patterns of alternative splicing during a host infection cycle.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2024-12-18 eCollection Date: 2024-12-01 DOI: 10.1371/journal.ppat.1012791

Alex Z Zaccaron, Li-Hung Chen, Ioannis Stergiopoulos

{"title":"Transcriptome analysis of two isolates of the tomato pathogen Cladosporium fulvum, uncovers genome-wide patterns of alternative splicing during a host infection cycle.","authors":"Alex Z Zaccaron, Li-Hung Chen, Ioannis Stergiopoulos","doi":"10.1371/journal.ppat.1012791","DOIUrl":"10.1371/journal.ppat.1012791","url":null,"abstract":"Alternative splicing (AS) is a key element of eukaryotic gene expression that increases transcript and proteome diversity in cells, thereby altering their responses to external stimuli and stresses. While AS has been intensively researched in plants and animals, its frequency, conservation, and putative impact on virulence, are relatively still understudied in plant pathogenic fungi. Here, we profiled the AS events occurring in genes of Cladosporium fulvum isolates Race 5 and Race 4, during nearly a complete compatible infection cycle on their tomato host. Our studies revealed extensive heterogeneity in the transcript isoforms assembled from different isolates, infections, and infection timepoints, as over 80% of the transcript isoforms were singletons that were detected in only a single sample. Despite that, nearly 40% of the protein-coding genes in each isolate were predicted to be recurrently AS across the disparate infection timepoints, infections, and the two isolates. Of these, 37.5% were common to both isolates and 59% resulted in multiple protein isoforms, thereby putatively increasing proteome diversity in the pathogen by 31% during infections. An enrichment analysis showed that AS mostly affected genes likely to be involved in the transport of nutrients, regulation of gene expression, and monooxygenase activity, suggesting a role for AS in finetuning adaptation of C. fulvum on its tomato host during infections. Tracing the location of the AS genes on the fungal chromosomes showed that they were mostly located in repeat-rich regions of the core chromosomes, indicating a causal connection between gene location on the genome and propensity to AS. Finally, multiple cases of differential isoform usage in AS genes of C. fulvum were identified, suggesting that modulation of AS at different infection stages may be another way by which pathogens refine infections on their hosts.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012791"},"PeriodicalIF":5.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694984/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fructose-1,6-diphosphate inhibits viral replication by promoting the lysosomal degradation of HMGB1 and blocking the binding of HMGB1 to the viral genome.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2024-12-18 eCollection Date: 2024-12-01 DOI: 10.1371/journal.ppat.1012782

Penghui Hu, Huiyi Li, Zemin Ji, Weijia Jing, Zihan Li, Sujun Yu, Xiao Shan, Yan Cui, Baochen Wang, Hongyuan Dong, Yanzhao Zhou, Zhe Wang, Hui Xiong, Xiaomei Zhang, Hui-Chieh Li, Jinrong Wang, Jiuzhou Tang, Ting Wang, Keliang Xie, Yuping Liu, Haizhen Zhu, Qiujing Yu

{"title":"Fructose-1,6-diphosphate inhibits viral replication by promoting the lysosomal degradation of HMGB1 and blocking the binding of HMGB1 to the viral genome.","authors":"Penghui Hu, Huiyi Li, Zemin Ji, Weijia Jing, Zihan Li, Sujun Yu, Xiao Shan, Yan Cui, Baochen Wang, Hongyuan Dong, Yanzhao Zhou, Zhe Wang, Hui Xiong, Xiaomei Zhang, Hui-Chieh Li, Jinrong Wang, Jiuzhou Tang, Ting Wang, Keliang Xie, Yuping Liu, Haizhen Zhu, Qiujing Yu","doi":"10.1371/journal.ppat.1012782","DOIUrl":"10.1371/journal.ppat.1012782","url":null,"abstract":"Fructose-1,6-diphosphate (FBP), a key glycolytic metabolite, is recognized for its cytoprotective effects during stress. However, the role of FBP in viral infections is unknown. Here, we demonstrate that virus-infected cells exhibit elevated FBP levels. Exogenous FBP inhibits both RNA and DNA virus infections in vitro and in vivo. Modulating intracellular FBP levels by regulating the expression of the metabolic enzymes FBP1 and PFK1 significantly impacts viral infections. Mechanistically, the inhibitory effects of FBP are not a result of altered viral adhesion or entry and are largely independent of type I interferon-mediated immune responses; rather, they occur through modulation of HMGB1. During viral infections, FBP predominantly reduces the protein levels of HMGB1 by facilitating its lysosomal degradation. Furthermore, FBP interacts with HMGB1 and disrupts the binding of HMGB1 to viral genomes, thereby further inhibiting viral replication. Our findings underscore the potential of FBP as a therapeutic target for controlling viral infections.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012782"},"PeriodicalIF":5.5,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11654956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Zinc homeostasis regulates caspase activity and inflammasome activation. 锌的平衡调节 Caspase 的活性和炎症小体的激活。

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2024-12-17 eCollection Date: 2024-12-01 DOI: 10.1371/journal.ppat.1012805

Xiao Gong, Weidi Gu, Shuo Fu, Gonglu Zou, Zhengfan Jiang

{"title":"Zinc homeostasis regulates caspase activity and inflammasome activation.","authors":"Xiao Gong, Weidi Gu, Shuo Fu, Gonglu Zou, Zhengfan Jiang","doi":"10.1371/journal.ppat.1012805","DOIUrl":"10.1371/journal.ppat.1012805","url":null,"abstract":"Inflammasome activation drives pyroptotic cell death and the release of inflammatory cytokines, and many diseases involve its overactivation. Zinc is essential for all organisms as a trace element, but its functions in innate immunity remain undefined. Here, we reported that Zn2+ inhibits caspase-1 to hinder inflammasome activation. We first identified the zinc exporter solute carrier family 30 member 1 (SLC30A1) as an inflammasome regulator, using a genome-wide CRISPR-Cas9-mediated screen. SLC30A1 deficiency suppressed multiple inflammasomes by increasing intracellular levels of Zn2+, which bound and inhibited caspase-1 at its active site residues H237, C244 and C285. Mutation of these residues almost completely blocked zinc binding. Similarly, Zn2+ also inhibited caspase-4/5/11-mediated noncanonical inflammasome activation. Importantly, zinc supplementation significantly relieved cecal ligation and puncture (CLP)-induced sepsis, Imiquimod (IMQ)-induced psoriasis and Alzheimer's disease. Thus, zinc might be used to treat inflammasome-related diseases as a broad-spectrum inflammasome inhibitor.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012805"},"PeriodicalIF":5.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11687882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","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 previously unidentified circRNA inhibits virus replication by regulating the miR-24-3p/KEAP1 axis. 一种以前未发现的 circRNA 通过调节 miR-24-3p/KEAP1 轴抑制病毒复制。

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2024-12-17 eCollection Date: 2024-12-01 DOI: 10.1371/journal.ppat.1012712

Haimin Li, Liuyang Du, Juan Li, Yanming Huang, Chenhe Lu, Tingjuan Deng, Yan Yan, Yulan Jin, Wei Wu, Jinyan Gu, Jiyong Zhou

{"title":"A previously unidentified circRNA inhibits virus replication by regulating the miR-24-3p/KEAP1 axis.","authors":"Haimin Li, Liuyang Du, Juan Li, Yanming Huang, Chenhe Lu, Tingjuan Deng, Yan Yan, Yulan Jin, Wei Wu, Jinyan Gu, Jiyong Zhou","doi":"10.1371/journal.ppat.1012712","DOIUrl":"10.1371/journal.ppat.1012712","url":null,"abstract":"Circular RNAs (circRNAs) exert diverse biological functions in different processes. However, the role of circRNAs during virus infection is mostly unknown. Herein, we explored the characteristics of host circRNAs using alphaherpesvirus pseudorabies virus (PRV) as a model. PRV infection upregulated the expression of circRNA circ29164, which does not encode a protein. RNA pulldown assays identified that circ29164 interacts with the microRNA ssc-miRNA-24-3p. Further analysis indicated that ssc-miR-24-3p targets the mRNA encoding kelch-like ECH-associated protein 1 (KEAP1), and circ29164 competitively binds to ssc-miR-24-3p to prevent it binding to Keap1. Apoptosis detection demonstrated that circ29164 or Keap1 overexpression, but not knockdown, induced caspase 3 activity and the release of cytochrome C from mitochondria, and inhibited PRV replication. Taken together, these data identified a previously undiscovered circRNA, circ29164, which inhibits PRV replication by competitively binding to ssc-24-3p to maintain KEAP1 levels.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012712"},"PeriodicalIF":5.5,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11651552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","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 2 faces of plant SUMOylation against viruses. 植物 SUMOylation 对抗病毒的两面性。

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2024-12-17 eCollection Date: 2024-12-01 DOI: 10.1371/journal.ppat.1012701

Blanca Sabarit, Eduardo R Bejarano

引用次数: 0

Activation of the tick Toll pathway to control infection of Ixodes ricinus by the apicomplexan parasite Babesia microti.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2024-12-16 eCollection Date: 2024-12-01 DOI: 10.1371/journal.ppat.1012743

Marie Jalovecka, Laurence Malandrin, Veronika Urbanova, Sazzad Mahmood, Pavla Snebergerova, Miriama Peklanska, Veronika Pavlasova, Radek Sima, Petr Kopacek, Jan Perner, Ondrej Hajdusek

{"title":"Activation of the tick Toll pathway to control infection of Ixodes ricinus by the apicomplexan parasite Babesia microti.","authors":"Marie Jalovecka, Laurence Malandrin, Veronika Urbanova, Sazzad Mahmood, Pavla Snebergerova, Miriama Peklanska, Veronika Pavlasova, Radek Sima, Petr Kopacek, Jan Perner, Ondrej Hajdusek","doi":"10.1371/journal.ppat.1012743","DOIUrl":"10.1371/journal.ppat.1012743","url":null,"abstract":"The vector competence of blood-feeding arthropods is influenced by the interaction between pathogens and the immune system of the vector. The Toll and IMD (immune deficiency) signaling pathways play a key role in the regulation of innate immunity in both the Drosophila model and blood-feeding insects. However, in ticks (chelicerates), immune determination for pathogen acquisition and transmission has not yet been fully explored. Here, we have mapped homologs of insect Toll and IMD pathways in the European tick Ixodes ricinus, an important vector of human and animal diseases. We show that most genes of the Toll pathway are well conserved, whereas the IMD pathway has been greatly reduced. We therefore investigated the functions of the individual components of the tick Toll pathway and found that, unlike in Drosophila, it was specifically activated by Gram-negative bacteria. The activation of pathway induced the expression of defensin (defIR), the first identified downstream effector gene of the tick Toll pathway. Borrelia, an atypical bacterium and causative agent of Lyme borreliosis, bypassed Toll-mediated recognition in I. ricinus and also resisted systemic effector molecules when the Toll pathway was activated by silencing its repressor cactus via RNA interference. Babesia, an apicomplexan parasite, also avoided Toll-mediated recognition. Strikingly, unlike Borrelia, the number of Babesia parasites reaching the salivary glands during tick infection was significantly reduced by knocking down cactus. The simultaneous silencing of cactus and dorsal resulted in greater infections and underscored the importance of tick immunity in regulating parasite infections in these important disease vectors.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012743"},"PeriodicalIF":5.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Climate change and Vibrio vulnificus dynamics: A blueprint for infectious diseases.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2024-12-16 eCollection Date: 2024-12-01 DOI: 10.1371/journal.ppat.1012767

Jane M Jayakumar, Jaime Martinez-Urtaza, Kyle D Brumfield, Antarpreet S Jutla, Rita R Colwell, Otto X Cordero, Salvador Almagro-Moreno

{"title":"Climate change and Vibrio vulnificus dynamics: A blueprint for infectious diseases.","authors":"Jane M Jayakumar, Jaime Martinez-Urtaza, Kyle D Brumfield, Antarpreet S Jutla, Rita R Colwell, Otto X Cordero, Salvador Almagro-Moreno","doi":"10.1371/journal.ppat.1012767","DOIUrl":"10.1371/journal.ppat.1012767","url":null,"abstract":"Climate change is having increasingly profound effects on human health, notably those associated with the occurrence, distribution, and transmission of infectious diseases. The number of disparate ecological parameters and pathogens affected by climate change are vast and expansive. Disentangling the complex relationship between these variables is critical for the development of effective countermeasures against its effects. The pathogen Vibrio vulnificus, a naturally occurring aquatic bacterium that causes fulminant septicemia, represents a quintessential climate-sensitive organism. In this review, we use V. vulnificus as a model organism to elucidate the intricate network of interactions between climatic factors and pathogens, with the objective of identifying common patterns by which climate change is affecting their disease burden. Recent findings indicate that in regions native to V. vulnificus or related pathogens, climate-driven natural disasters are the chief contributors to their disease outbreaks. Concurrently, climate change is increasing the environmental suitability of areas non-endemic to their diseases, promoting a surge in their natural populations and transmission dynamics, thus elevating the risk of new outbreaks. We highlight potential risk factors and climatic drivers aggravating the threat of V. vulnificus transmission under both scenarios and propose potential measures for mitigating its impact. By defining the mechanisms by which climate change influences V. vulnificus disease burden, we aim to shed light on the transmission dynamics of related disease-causing agents, thereby laying the groundwork for early warning systems and broadly applicable control measures.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012767"},"PeriodicalIF":5.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sniffer restricts arboviral brain infections by regulating ROS levels and protecting blood-brain barrier integrity in Drosophila and mosquitoes.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2024-12-16 DOI: 10.1371/journal.ppat.1012797

Rui Hu, Mengzhu Li, Shulin Chen, Man Wang, Xinjun Tao, Yihan Zhu, Huan Yan, Yuan Liu

{"title":"Sniffer restricts arboviral brain infections by regulating ROS levels and protecting blood-brain barrier integrity in Drosophila and mosquitoes.","authors":"Rui Hu, Mengzhu Li, Shulin Chen, Man Wang, Xinjun Tao, Yihan Zhu, Huan Yan, Yuan Liu","doi":"10.1371/journal.ppat.1012797","DOIUrl":"10.1371/journal.ppat.1012797","url":null,"abstract":"Arthropod-borne viruses (arboviruses) are transmitted to humans by arthropod vectors and pose a serious threat to global public health. Neurotropic arboviruses including Sindbis virus (SINV) persistently infect the central nervous system (CNS) of vector insects without causing notable pathological changes or affecting their behavior or lifespan. However, the mechanisms by which vector insects evade these viral infections in the brains are poorly understood. In this study, we found that loss of the carbonyl reductase Sniffer (Sni) led to a significant increase in SINV infection in the Drosophila brain. Sni regulates reactive oxygen species (ROS) levels, and its depletion leads to elevated ROS, which in turn disrupts the septate junctions (SJs) between subperineurial glia (SPG) cells, compromising the integrity and barrier function of the blood-brain barrier (BBB). Genetic and pharmacological reduction of ROS restored BBB integrity and reduced viral load in the brains of Sni-depleted flies. Additionally, we identified Sni homologs and revealed that the antiviral function of Sni is highly conserved in mosquitoes, where it regulates ROS and protects BBB integrity. Our results revealed an evolutionarily conserved antiviral mechanism in which Sni acts as an antioxidant that protects BBB integrity and restricts viral infection in the vector insect brain.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012797"},"PeriodicalIF":5.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142840156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep phosphoproteomics of Klebsiella pneumoniae reveals HipA-mediated tolerance to ciprofloxacin. 肺炎克雷伯氏菌的深度磷蛋白组学揭示了 HipA 介导的环丙沙星耐受性。

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2024-12-12 DOI: 10.1371/journal.ppat.1012759

Payal Nashier, Isabell Samp, Marvin Adler, Fiona Ebner, Lisa Thai Lê, Marc Göppel, Carsten Jers, Ivan Mijakovic, Sandra Schwarz, Boris Macek

{"title":"Deep phosphoproteomics of Klebsiella pneumoniae reveals HipA-mediated tolerance to ciprofloxacin.","authors":"Payal Nashier, Isabell Samp, Marvin Adler, Fiona Ebner, Lisa Thai Lê, Marc Göppel, Carsten Jers, Ivan Mijakovic, Sandra Schwarz, Boris Macek","doi":"10.1371/journal.ppat.1012759","DOIUrl":"https://doi.org/10.1371/journal.ppat.1012759","url":null,"abstract":"Klebsiella pneumoniae belongs to the group of bacterial pathogens causing the majority of antibiotic-resistant nosocomial infections worldwide; however, the molecular mechanisms underlying post-translational regulation of its physiology are poorly understood. Here we perform a comprehensive analysis of Klebsiella phosphoproteome, focusing on HipA, a Ser/Thr kinase involved in antibiotic tolerance in Escherichia coli. We show that overproduced K. pneumoniae HipA (HipAkp) is toxic to both E. coli and K. pneumoniae and its toxicity can be rescued by overproduction of the antitoxin HipBkp. Importantly, HipAkp overproduction leads to increased tolerance against ciprofloxacin, a commonly used antibiotic in the treatment of K. pneumoniae infections. Proteome and phosphoproteome analyses in the absence and presence of ciprofloxacin confirm that HipAkp has Ser/Thr kinase activity, auto-phosphorylates at S150, and shares multiple substrates with HipAec, thereby providing a valuable resource to clarify the molecular basis of tolerance and the role of Ser/Thr phosphorylation in this human pathogen.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012759"},"PeriodicalIF":5.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure of the Pseudomonas aeruginosa PAO1 Type IV pilus.

IF 5.5 1区医学

PLoS Pathogens Pub Date : 2024-12-12 eCollection Date: 2024-12-01 DOI: 10.1371/journal.ppat.1012773

Hannah Ochner, Jan Böhning, Zhexin Wang, Abul K Tarafder, Ido Caspy, Tanmay A M Bharat

{"title":"Structure of the Pseudomonas aeruginosa PAO1 Type IV pilus.","authors":"Hannah Ochner, Jan Böhning, Zhexin Wang, Abul K Tarafder, Ido Caspy, Tanmay A M Bharat","doi":"10.1371/journal.ppat.1012773","DOIUrl":"10.1371/journal.ppat.1012773","url":null,"abstract":"Type IV pili (T4Ps) are abundant in many bacterial and archaeal species, where they play important roles in both surface sensing and twitching motility, with implications for adhesion, biofilm formation and pathogenicity. While Type IV pilus (T4P) structures from other organisms have been previously solved, a high-resolution structure of the native, fully assembled T4P of Pseudomonas aeruginosa, a major human pathogen, would be valuable in a drug discovery context. Here, we report a 3.2 Å-resolution structure of the P. aeruginosa PAO1 T4P determined by electron cryomicroscopy (cryo-EM). PilA subunits constituting the T4P exhibit a classical pilin fold featuring an extended N-terminal α-helix linked to a C-terminal globular β-sheet-containing domain, which are packed tightly along the pilus, in line with models derived from previous cryo-EM data of the P. aeruginosa PAK strain. The N-terminal helices constitute the pilus core where they stabilise the tubular assembly via hydrophobic interactions. The α-helical core of the pilus is surrounded by the C-terminal globular domain of PilA that coats the outer surface of the pilus, mediating interactions with the surrounding environment. Comparison of the P. aeruginosa PAO1 T4P with T4P structures from other organisms, both at the level of the pilin subunits and the fully assembled pili, confirms previously described common architectural principles whilst highlighting key differences between members of this abundant class of prokaryotic filaments. This study provides a structural framework for understanding the molecular and cell biology of these important cellular appendages mediating interaction of prokaryotes to surfaces.","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":"20 12","pages":"e1012773"},"PeriodicalIF":5.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142819403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0