mSphere最新文献

{"title":"Characterization of the ligand binding pocket of the virulence regulator Rns, a member of the AraC/XylS family of transcription factors.","authors":"Jessica D Tolbert, Kacey M Talbot, Christopher M Bollinger, F Jon Kull, George P Munson, Charles R Midgett","doi":"10.1128/msphere.00115-25","DOIUrl":"https://doi.org/10.1128/msphere.00115-25","url":null,"abstract":"<p><p>Diarrheal disease caused by Gram-negative enteric pathogens, such as enterotoxigenic <i>Escherichia coli</i> (ETEC), <i>Vibrio cholerae</i>, <i>Shigella</i> spp., and <i>Salmonella</i> spp., is a leading cause of morbidity and mortality of children, especially in low resource nations. While progress has been made in reducing this burden, there remains a need to develop effective therapies. Recently, we determined the structure of Rns, a member of the AraC/XylS family that regulates the expression of pili and other virulence factors in ETEC. The structure revealed decanoic acid bound between the N- and C-terminal domains. To test the hypothesis that bound decanoic acid directly inhibits Rns, we identified amino acid side chains predicted to be necessary for ligand binding. Removal of the positive side chains of R75 and H20 rendered Rns insensitive to fatty acid inhibition. Additionally, mutations designed to block decanoic acid binding also produced a variant Rns that was fatty acid insensitive. We also observed that this variant is structurally more flexible than wildtype Rns bound to decanoic acid, suggesting that fatty acid binding contributes to structural rigidity. These studies demonstrate that Rns binding pocket residues are critical for binding fatty acids, which result in inhibition of DNA binding and support our hypothesis that fatty acids must bind in the binding pocket to inhibit other AraC regulators. Further work by us and others suggests that inhibition of AraC virulence regulators by fatty acids is a common paradigm among many bacterial pathogens. Therefore, understanding the molecular basis of inhibition lays the groundwork for the development of small molecule therapeutics targeting enteric disease.</p><p><strong>Importance: </strong>As antimicrobial resistance increases, it is critical to develop new strategies to combat these infections. One area of concern is bacteria that cause intestinal disease such as <i>Salmonella</i> species, <i>Vibrio cholerae</i>, <i>Shigella</i> species, and enterotoxigenic <i>Escherichia coli</i> (ETEC). ETEC is a leading cause of travelers' diarrheal disease and a leading cause of mortality for children under 5 years old. To cause disease, ETEC requires the gene regulator Rns. Our previous work found that Rns was inhibited by a fatty acid. Here, we identify key features in the protein that are required for not only binding fatty acids but also for responding to them. This was done through a combination of microbiological as well as structural techniques of altered Rns proteins that can no longer bind fatty acid. Understanding how Rns is inhibited will lead to new ideas about how to target this class of proteins without causing antimicrobial resistance.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0011525"},"PeriodicalIF":3.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of V3-V4 and FL-16S rRNA amplicon sequencing approach for microbiota community analysis of tracheostomy aspirates.","authors":"A Gupta, V S Cooper, A C Zemke","doi":"10.1128/msphere.00388-25","DOIUrl":"https://doi.org/10.1128/msphere.00388-25","url":null,"abstract":"<p><p>Respiratory infections pose a significant risk for people requiring prolonged mechanical ventilation, yet limited information exists regarding the complex microbiome dynamics of people with tracheostomies during chronic critical illness. Oxford Nanopore Technologies (ONT) long-read sequencing allows for full-length 16S rRNA amplicon sequencing, providing enhanced species-level understanding of the respiratory microbiome. We validated ONT-based FL-16S amplicon sequencing for microbial insights from tracheal aspirates by comparing results with those of Illumina V3-V4 amplicon sequencing. Comparisons were made on a standardized microbial community and tracheal aspirates using multiple DNA extraction kits. Conventional short-read bioinformatic pipelines are suboptimal for processing longer, error-prone ONT reads. The Emu bioinformatics pipeline, specifically designed for ONT FL-16S reads, enhances the accuracy but necessitates validation for tracheal aspirates. In this study, we compared the analysis of FL-16S reads using Emu to the standardized V3-V4 read analysis with QIIME2. Our findings demonstrate that at the same sequencing read depth, FL-16S sequencing analysis with Emu yields comparable alpha and taxonomic diversity metrics, while providing superior species-level resolution compared to V3-V4 amplicon sequencing of tracheal aspirates. Our results show that tracheal aspirates during chronic critical illness are low-diversity samples, with most pathogenic genera represented by a single species. However, members of the oral microbiota <i>Streptococcus</i> and <i>Prevotella</i> are represented by multiple species.</p><p><strong>Importance: </strong>The role of the respiratory microbiome in shaping outcomes for patients with chronic critical illness undergoing prolonged mechanical ventilation via a tracheostomy remains poorly understood, despite its potential to drive infections and complicate recovery. Current methods, such as short-read 16S rRNA sequencing, lack taxonomic resolution to track pathogens at the species level, limiting clinical insights. Our study addresses this gap by validating ONT-based full-length (FL)-16S rRNA sequencing, a method that achieves species-level taxonomic precision critical for analyzing complex respiratory microbiomes. We benchmarked the microbiome composition of tracheal aspirates from ONT FL-16S rRNA workflows against Illumina V3-V4 data to demonstrate that long-read sequencing delivers comparable diversity profiles while resolving species-level diversity of clinically relevant species and microbes associated with the oral microbiome.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0038825"},"PeriodicalIF":3.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A possible turning point for research governance in the life sciences.","authors":"David R Gillum","doi":"10.1128/msphere.00407-25","DOIUrl":"https://doi.org/10.1128/msphere.00407-25","url":null,"abstract":"<p><p>On 5 May 2025, the White House issued Executive Order (EO) 14292, halting federally funded \"dangerous gain-of-function\" research and rescinding the 2024 Dual Use Research of Concern (DURC) and Pathogens with Enhanced Pandemic Potential (PEPP) policy. While intended to strengthen biosafety and biosecurity, the EO introduces vague definitions, an abrupt 120-day policy development deadline, and politically charged rhetoric that could undermine trust and buy-in. Researchers, biosafety professionals, and institutions are left with a biosecurity policy vacuum after this EO, which is creating uncertainty across the scientific enterprise. This perspective considers the EO's implications through empirical findings and practitioner insight and argues for a tiered, adaptive risk governance model grounded in scientific rigor, operational clarity, and institutional expertise to navigate future biosecurity challenges.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0040725"},"PeriodicalIF":3.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive characterization of the impairing effects of <i>Nosema bombycis</i> on the host digestive integrity and function.","authors":"Lu Cao, Siying Yin, Dexu Liu, Yunlin Tang, Wenxin Yang, Maoshuang Ran, Jie Chen, Guoqing Pan, Zeyang Zhou, Jialing Bao","doi":"10.1128/msphere.00095-25","DOIUrl":"https://doi.org/10.1128/msphere.00095-25","url":null,"abstract":"<p><p><i>Nosema bombycis</i> (<i>N. bombycis</i>) infection causes growth retardation and indigestion of silkworms (<i>Bombyx mori</i>). The digestive tract is the primary infection route; thereby, in this study, we comprehensively investigated the disturbances of the digestive tract upon <i>N. bombycis</i> infection. Electron microscopy demonstrated the structure and integrity impairments of the peritrophic membrane and midgut after infection. A quantitative proteomic approach identified approximately 2,893 dysregulated proteins in the midgut after infection. Next, 16S rRNA and ITS analysis of the digestive juice and stool samples revealed that the gut microbiome profiles were significantly disturbed, such as bacterial genus <i>Acinetobacter</i>, <i>Staphylococcus,</i> as well as eukaryotic <i>Penicillium</i>, <i>Chaetasbolisia,</i> and so on. In addition, various digestive enzyme expressions were also disturbed upon <i>N. bombycis</i> infection. More interestingly, we found that chitin deacetylase BmCDA8, one of the top dysregulated host proteins, functioned as the key protective enzyme against <i>N. bombycis</i> since knocking down BmCDA8 leads to increased barrier permeability and higher <i>N. bombycis</i> loads. We also identified 24 <i>N</i>. <i>bombycis</i> proteins that would potentially interact with BmCDA8. Taken together, our investigation will help to fully elucidate the impairing effects of <i>N. bombycis</i> on host and to identify novel pathogen control targets.IMPORTANCEThe digestive tract is the major infection route of many pathogens. A comprehensive view of the impairing effects of <i>N. bombycis</i> on <i>B. mori</i>'s digestive tract integrity, microbiome, and enzyme compositions is greatly needed. Therefore, we applied electron microscopy, quantitative proteomics, and microbiome analysis to clearly demonstrate that <i>N. bombycis</i> infections did impair host intestinal integrity, changed the gut microbiome composition, and dysregulated digestive enzymes. Interestingly, we found that the chitin deacetylase of <i>B. mori</i> exerts an essential protective role, and <i>N. bombycis</i> effector proteins may interact directly with it to facilitate the impairing effects. Our findings provide a comprehensive view and decode the phenomena of silkworm indigestion and growth retardation after <i>N. bombycis</i> infection and will provide potential targets for disease prevention and control.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0009525"},"PeriodicalIF":3.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Variation in virulence between three representative <i>Bordetella pertussis</i> pertactin-negative clinical isolates.","authors":"Nicole Lamond, Lindsey Zimmerman, Yihui Wang, Jonatan Maldonado Villeda, Asgeir Bjarnason, Hekla Bryndís Jóhannsdóttir, Tami H Skoff, Maria-Lucia Tondella, Michael R Weigand, Susan Hariri, Tod Merkel","doi":"10.1128/msphere.00310-25","DOIUrl":"https://doi.org/10.1128/msphere.00310-25","url":null,"abstract":"<p><p>Pertussis is a respiratory disease caused by the bacterium <i>Bordetella pertussis</i>. Acellular pertussis (aP) vaccines replaced more reactogenic whole-cell pertussis (wP) vaccines in the United States in the 1990s. Despite high rates of vaccination, a slow but consistent increase in the number of U.S. pertussis cases was observed starting in the 1980s that accelerated following the introduction of aP vaccines. Most aP vaccines contain pertussis toxoid (PT), filamentous hemagglutinin (FHA), and pertactin (PRN), and some contain fimbriae (FIM 2/3). Countries that transitioned into aP vaccines have observed increasing rates of pertactin-negative (PRN^NEG) clinical isolates, exceeding 85% in some countries. This outcome suggests <i>B. pertussis</i> does not require PRN, and immune responses against PRN may impact <i>B. pertussis</i> circulation. With the high prevalence of PRN^NEG strains circulating in the United States, we sought to identify an acceptable PRN^NEG strain for use in baboon challenge studies and controlled human infection model (CHIM) studies. Baboons were challenged with the PRN-positive (PRN^POS) strain D420 or one of three PRN^NEG strains selected to represent the genetic diversity of <i>B. pertussis</i> strains circulating in the United States. Despite comparable levels of colonization between the animals infected with the PRN^NEG strains and D420, there was variability between the three PRN^NEG strains with respect to virulence, and two of the three strains appeared reduced in one or more measures of virulence. These findings suggest that some PRN^NEG clinical isolates may be less virulent than D420 and suggest care should be taken when selecting strains for baboon and CHIM studies.IMPORTANCEWith the increased circulation of <i>Bordetella pertussis</i> PRN^NEG strains in countries using acellular pertussis (aP) vaccines, understanding the epidemiology and pathogenesis of PRN^NEG strains is critical. Our results suggest that virulence varies between circulating PRN^NEG strains, with some strains appearing to be less virulent than PRN^POS strains. These results tell us that care should be taken when selecting PRN^NEG pertussis strains for baboon and CHIM studies. Our results may also support the continued use of PRN in aP vaccines. If PRN^NEG strains are less virulent and induce less severe disease than PRN^POS strains, maintaining vaccine selective pressure against PRN^POS strains may be beneficial.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0031025"},"PeriodicalIF":3.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of tropodithietic acid on microbial physiology under varying culture complexities.","authors":"Olesia Shlakhter, Sergey Malitsky, Einat Segev","doi":"10.1128/msphere.00138-25","DOIUrl":"https://doi.org/10.1128/msphere.00138-25","url":null,"abstract":"<p><p>Understanding marine bacterial physiology under environmentally relevant conditions requires the study of biotic interactions across systems of varying complexities. Here, we examine how the capability of <i>Phaeobacter inhibens</i> bacteria to produce tropodithietic acid (TDA), a secondary metabolite, influences microbial physiology and interactions. Our systematic approach, which includes progressing from bacterial monocultures to co-cultures and tri-cultures involving algal hosts, allows us to evaluate the impact of the <i>tdaB</i> gene and the TDA metabolite on microbial interactions. Our findings show that deleting the <i>tdaB</i> gene resulted in no detectable TDA production and affected bacteria-bacteria interactions in co-culture but not in tri-cultures with the algal host. Additionally, our data reveal that algal death was delayed in cultures containing <i>P. inhibens</i> Δ<i>tdaB</i> mutants compared to those with wild-type bacteria, although no TDA was detected in these tri-cultures. The findings of our study highlight the importance of microbial complexity in the study of bacterial physiology and point to the understudied role of TDA in microbial interactions.IMPORTANCELaboratory model systems enable controlled studies of marine microbial processes; however, the microbial complexity of the culture can influence the outcome. In this study, we employ a systematic approach to assess the impact of the bacterial ability to produce the antibiotic TDA in laboratory cultures with varying microbial complexities (from bacterial monocultures to bacterial co-cultures and algal-bacterial tri-cultures). Our findings demonstrate altered effects of the <i>tdaB</i> gene deletion with increasing microbial complexity, showing distinct impacts on microbial fitness. Since antibiotics like TDA mediate microbial interactions, it is important to examine them within ecologically relevant model systems that reflect inter- and intra-trophic interactions, including bacteria-bacteria and algae-bacteria relationships. Overall, our study highlights the importance of accounting for culture complexity when designing laboratory experiments to investigate microbial interactions and the compounds that mediate them.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0013825"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Straining to define a healthy microbiome.","authors":"Anna M Seekatz","doi":"10.1128/msphere.00797-24","DOIUrl":"https://doi.org/10.1128/msphere.00797-24","url":null,"abstract":"<p><p>In 2020, I wrote an mSphere of Influence commentary on two studies that shaped my research perspective on the human gut microbiome (McNulty et al., Sci Transl Med 3:106ra106, 2011, https://doi.org/10.1126/scitranslmed.3002701; Hamilton et al., Gut Microbes 4:125, 2013, https://doi.org/10.4161/gmic.23571). The microbiome field has continued to progress since the publication of these studies over 10 years ago, emerging as a considerable factor in almost all areas focused on disease development. My previous commentary highlighted two areas that piqued my interest early on in my career: (i) that the extant microbial community should be considered when proposing to manipulate the microbiota, such as via probiotics or fecal microbiota transplantation, and (ii) that realized (i.e., transcribed) functional changes of the microbiota may occur independent of changes in its composition. Since writing that commentary, two microbiota-based therapeutics for the treatment of <i>Clostridioides difficile</i> infection have been approved, highlighting the potential success of using the microbiota to treat or prevent disease. Despite these wins and ever-growing evidence of the importance of the microbiome in managing our health, translating mechanistic studies into therapeutic value has been slower. In this minireview, I expand upon two large questions that would increase our ability to translate the microbiome into therapies, highlighting both historical and recent progress.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0079724"},"PeriodicalIF":3.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global phylogeography and microdiversity of the marine diazotrophic photoautotrophs <i>Trichodesmium</i> and UCYN-A.","authors":"Angie Nguyen, Lucas J Ustick, Alyse A Larkin, Adam C Martiny","doi":"10.1128/msphere.00245-25","DOIUrl":"10.1128/msphere.00245-25","url":null,"abstract":"<p><p>Photoautotrophic diazotrophs, specifically the genera <i>Trichodesmium</i> and UCYN-A, play a pivotal role in marine nitrogen cycling through their capacity for nitrogen fixation. Despite their global distribution, the microdiversity and environmental drivers of these diazotrophs remain underexplored. This study provides a comprehensive analysis of the global diversity and distribution of <i>Trichodesmium</i> and UCYN-A using the nitrogenase gene (<i>nifH</i>) as a genetic marker. We sequenced 954 samples from the Pacific, Atlantic, and Indian Oceans as part of the Bio-GO-SHIP project. Our results reveal significant phylogenetic and biogeographic differences between and within the two genera. <i>Trichodesmium</i> exhibited greater microdiversity compared to UCYN-A, with clades showing region-specific distribution. <i>Trichodesmium</i> clades were primarily influenced by temperature and nutrient availability. They were particularly frequent in regions of phosphorus stress. In contrast, UCYN-A was most frequently observed in regions experiencing iron stress. UCYN-A clades demonstrated more homogeneous distributions, with a single sequence variant within the UCYN-A1 clade dominating across varied environments. The biogeographic patterns and environmental correlations of <i>Trichodesmium</i> and UCYN-A highlight the role of microdiversity in their ecological adaptation and reflect their different ecological strategies. These findings underscore the importance of characterizing the global patterns of fine-scale genetic diversity to better understand the functional roles and distribution of marine nitrogen-fixing photoautotrophs.IMPORTANCEThis study provides insights into the global diversity and distribution of nitrogen-fixing photoautotrophs, specifically <i>Trichodesmium</i> and UCYN-A. We sequenced 954 oceanic samples of the <i>nifH</i> nitrogenase gene and uncovered significant differences in microdiversity and environmental associations between these genera. <i>Trichodesmium</i> showed high levels of sequence diversity and region-specific clades influenced by temperature and nutrient availability. In contrast, UCYN-A exhibited a more uniform distribution, thriving in iron-stressed regions. Quantifying these fine-scale genetic variations enhances our knowledge of their ecological roles and adaptations, emphasizing the need to characterize the genetic diversity of marine nitrogen-fixing prokaryotes.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0024525"},"PeriodicalIF":3.7,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The <i>Plasmodium falciparum</i> homolog of Vps16 interacts with the core members of the Vps-C tethering complex.","authors":"Florian Lauruol, Thomas Galaup, Alexandra Bourgeois, Audrey Sergerie, Dave Richard","doi":"10.1128/msphere.00287-25","DOIUrl":"https://doi.org/10.1128/msphere.00287-25","url":null,"abstract":"<p><p>The organelles of the apical complex (rhoptries, micronemes, and dense granules) are critical for erythrocyte invasion by the malaria parasite <i>Plasmodium falciparum</i>. Though they have essential roles in the parasite lifecycle, the mechanisms behind their biogenesis are still poorly defined. The Class C Vps proteins Vps11, Vps16, Vps18, and Vps33 constitute the core of the CORVET and HOPS complexes implicated in vesicle tethering and fusion in the eukaryotic endolysosomal system. Work in the model apicomplexan <i>Toxoplasma gondii</i> has revealed that TgVps11 is essential for the generation of the apical complex. <i>P. falciparum</i> possesses all four subunits of the Vps-C complex, and recent work has shown that some of its components were critical for host-cell cytosol trafficking and the biogenesis of the apical complex. We here show that the <i>P. falciparum</i> ortholog of Vps16, a member of the Vps-C complex, is expressed throughout the asexual erythrocytic cycle and that it is potentially associated with the Golgi apparatus and the rhoptries in schizont stage parasites. We then demonstrate by immunoprecipitation and mass spectrometry that PfVps16 interacts with all the members of the canonical Vps-C complex along with the Vps3 CORVET component. Interestingly, three uncharacterized <i>Plasmodium</i>-specific proteins are also found as interactors of PfVps16, and structural predictions revealed that two of them possess folds commonly found in proteins present in membrane tethering complexes. These findings suggest that <i>P. falciparum</i> may possess both conserved and parasite-specific features within its endosomal tethering machinery.IMPORTANCEThe malaria parasite relies on special compartments to invade red blood cells. These are key to the parasite's ability to infect, but how these are generated is not well known. In eukaryotic cells, certain protein assemblies, called tethering complexes, help move and fuse small transport vesicles, which is important for building and maintaining organelles. <i>Plasmodium falciparum</i> possesses some of these proteins, and recent studies suggest they play an important role in building its infection machinery and transporting material inside the parasite. We found that the malaria parasite possesses additional components associated with the typical tethering proteins and that these are not found in other eukaryotes. These results suggest that <i>P. falciparum</i> uses both common and unique tools to create the cellular machinery it needs to infect red blood cells. We propose that the <i>Plasmodium</i>-specific components might represent interesting targets for the development of antimalarials with potentially reduced side effects since they are not present in humans.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0028725"},"PeriodicalIF":3.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LINC2781 enhances antiviral immunity against coxsackievirus B5 infection by activating the JAK-STAT pathway and blocking G3BP2-mediated STAT1 degradation.","authors":"Jiayu Zhang, Jing Li, Yonghan Luo, Timothy J Mahony, Jingru Gao, Yanchun Wang, Xiaotao Yang, Fan Yang, Xia Ou, Jihong Zhang, Heng Yang, Wei Chen","doi":"10.1128/msphere.00062-25","DOIUrl":"https://doi.org/10.1128/msphere.00062-25","url":null,"abstract":"<p><p>Coxsackievirus B5 (CVB5) is a primary causative agent of hand, foot, and mouth disease (HFMD), and some cases are also associated with severe complications through invasion of the central nervous system, resulting in death. Currently, there are no specific antiviral drugs or effective vaccines available for CVB5. Long non-coding RNAs (lncRNAs) have been shown to play significant roles in various diseases. In our research, we identified a novel lncRNA, LINC2781, which is significantly upregulated during CVB5 infection of SH-SY5Y cells. Characteristic analysis showed that LINC2781 is mainly located in the cytoplasm of infected cells, with significantly higher expression in the intestines and the spleen of CVB5-infected mice. Functional studies revealed that LINC2781 activates the JAK-STAT pathway via STAT1, promoting the expression of interferon-stimulated genes (ISGs) and inhibiting CVB5 replication. Mechanistically, LINC2781 directly binds to GTPase-activating protein SH3 domain-binding protein 2 (G3BP2), preventing G3BP2-mediated degradation of STAT1 through ubiquitination. <i>In vivo</i>, LINC2781 was shown to reduce the susceptibility of BALB/c mice to viral infection and alleviate viral-induced damage in both the intestines and the spleen. Clinical samples further confirmed a strong correlation between the expression of LINC2781 and CVB5 infection. Our findings demonstrate that CVB5-induced LINC2781 enhances STAT1 activation by blocking the suppressive effects of G3BP2 on immune responses, providing a potential foundation for developing antiviral therapies targeting the lncRNA.</p><p><strong>Importance: </strong>We investigate the role of lncRNA in virus-host interactions and identify a novel cytoplasmic lncRNA, LINC2781, whose expression is upregulated following CVB5 infection. LINC2781 specifically binds to G3BP2, preventing G3BP2 from degrading STAT1, thereby activating the JAK-STAT pathway, promoting the expression of ISGs, and ultimately inhibiting viral replication. Meanwhile, a strong correlation exists between the expression of LINC2781 and CVB5 infection in cells and clinical samples.</p>","PeriodicalId":19052,"journal":{"name":"mSphere","volume":" ","pages":"e0006225"},"PeriodicalIF":3.7,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}