PLoS Pathogens最新文献

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Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression. 爱泼斯坦-巴氏病毒再活化可通过溶解过程诱导不同的终止、重编程和宿主关闭状态。
IF 5.5 1区 医学
PLoS Pathogens Pub Date : 2024-10-24 DOI: 10.1371/journal.ppat.1012341
Elliott D SoRelle, Lauren E Haynes, Katherine A Willard, Beth Chang, James Ch'ng, Heather Christofk, Micah A Luftig
{"title":"Epstein-Barr virus reactivation induces divergent abortive, reprogrammed, and host shutoff states by lytic progression.","authors":"Elliott D SoRelle, Lauren E Haynes, Katherine A Willard, Beth Chang, James Ch'ng, Heather Christofk, Micah A Luftig","doi":"10.1371/journal.ppat.1012341","DOIUrl":"10.1371/journal.ppat.1012341","url":null,"abstract":"<p><p>Viral infection leads to heterogeneous cellular outcomes ranging from refractory to abortive and fully productive states. Single cell transcriptomics enables a high resolution view of these distinct post-infection states. Here, we have interrogated the host-pathogen dynamics following reactivation of Epstein-Barr virus (EBV). While benign in most people, EBV is responsible for infectious mononucleosis, up to 2% of human cancers, and is a trigger for the development of multiple sclerosis. Following latency establishment in B cells, EBV reactivates and is shed in saliva to enable infection of new hosts. Beyond its importance for transmission, the lytic cycle is also implicated in EBV-associated oncogenesis. Conversely, induction of lytic reactivation in latent EBV-positive tumors presents a novel therapeutic opportunity. Therefore, defining the dynamics and heterogeneity of EBV lytic reactivation is a high priority to better understand pathogenesis and therapeutic potential. In this study, we applied single-cell techniques to analyze diverse fate trajectories during lytic reactivation in three B cell models. Consistent with prior work, we find that cell cycle and MYC expression correlate with cells refractory to lytic reactivation. We further found that lytic induction yields a continuum from abortive to complete reactivation. Abortive lytic cells upregulate NFκB and IRF3 pathway target genes, while cells that proceed through the full lytic cycle exhibit unexpected expression of genes associated with cellular reprogramming. Distinct subpopulations of lytic cells further displayed variable profiles for transcripts known to escape virus-mediated host shutoff. These data reveal previously unknown and promiscuous outcomes of lytic reactivation with broad implications for viral replication and EBV-associated oncogenesis.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511102","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
A novel broad-spectrum antibacterial and anti-malarial Anopheles gambiae Cecropin promotes microbial clearance during pupation. 一种新型广谱抗菌和抗疟冈比亚按蚊 Cecropin 能促进蛹化过程中的微生物清除。
IF 5.5 1区 医学
PLoS Pathogens Pub Date : 2024-10-23 eCollection Date: 2024-10-01 DOI: 10.1371/journal.ppat.1012652
Cairé Barreto, Victor Cardoso-Jaime, George Dimopoulos
{"title":"A novel broad-spectrum antibacterial and anti-malarial Anopheles gambiae Cecropin promotes microbial clearance during pupation.","authors":"Cairé Barreto, Victor Cardoso-Jaime, George Dimopoulos","doi":"10.1371/journal.ppat.1012652","DOIUrl":"10.1371/journal.ppat.1012652","url":null,"abstract":"<p><p>Anophelinae mosquitoes are exposed to a variety of microbes including Plasmodium parasites that cause malaria. When infected, mosquitoes mount versatile immune responses, including the production of antimicrobial peptides. Cecropins are one of the most widely distributed families of antimicrobial peptides in insects and all previously studied Anopheles members are playing roles in adult mosquito immunity. We have identified and characterized a novel member of the Anopheles gambiae cecropin family, cecropin D (CecD), that is uniquely expressed and immune-responsive at late larval stages to promote microbial clearance through its broad-spectrum antibacterial activity during larval-pupal developmental transition. Interestingly, Cecropin D also exhibited highly potent activity against Plasmodium falciparum sporozoites, the malaria parasite stage that is transmitted from mosquitoes and infects humans and thereby holds promise as a malaria transmission-blocking agent. Finally, we have defined unequivocal cecropin-specific molecular signatures to systematically organize the diversity of the cecropin family in malaria vectors.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11554196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511089","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 host tropism of current zoonotic H7N9 viruses depends mainly on an acid-labile hemagglutinin with a single amino acid mutation in the stalk region. 目前人畜共患病 H7N9 病毒的宿主趋向性主要取决于一种在柄区有单个氨基酸突变的酸性嗜酸性血凝素。
IF 5.5 1区 医学
PLoS Pathogens Pub Date : 2024-10-22 eCollection Date: 2024-10-01 DOI: 10.1371/journal.ppat.1012427
Tomo Daidoji, Hiroki Sadakane, Kotaro Garan, Norihito Kawashita, Yasuha Arai, Yohei Watanabe, Takaaki Nakaya
{"title":"The host tropism of current zoonotic H7N9 viruses depends mainly on an acid-labile hemagglutinin with a single amino acid mutation in the stalk region.","authors":"Tomo Daidoji, Hiroki Sadakane, Kotaro Garan, Norihito Kawashita, Yasuha Arai, Yohei Watanabe, Takaaki Nakaya","doi":"10.1371/journal.ppat.1012427","DOIUrl":"https://doi.org/10.1371/journal.ppat.1012427","url":null,"abstract":"<p><p>The incidence of human infection by zoonotic avian influenza viruses, especially H5N1 and H7N9 viruses, has increased. Current zoonotic H7N9 avian influenza viruses (identified since 2013) emerged during reassortment of viruses belonging to different subtypes. Despite analyses of their genetic background, we do not know why current H7N9 viruses are zoonotic. Therefore, there is a need to identify the factor(s) responsible for the extended host tropism that enables these viruses to infect humans as well as birds. To identify H7N9-specific amino acids that confer zoonotic properties on H7N9 viruses, we performed multiple alignment of the hemagglutinin (HA) amino acid sequences of A/Shanghai/1/2013 (H7N9) and A/duck/Zhejiang/12/2011(H7N3) (a putative, non- or less zoonotic HA donor to the zoonotic H7N9 virus). We also analyze the function of an H7N9 HA-specific amino acid with respect to HA acid stability, and evaluated the effect of acid stability on viral infectivity and virulence in a mouse model. HA2-116D, preserved in current zoonotic H7N9 viruses, was crucial for loss of HA acid stability. The acid-labile HA protein in H7 viruses played an important role in infection of human airway epithelial cells; HA2-116D contributed to infection and replication of H7 viruses. Finally, HA2-116D served as a H7 virulence factor in mice. These results suggest that acid-labile HA harboring HA2-116D confers zoonotic characteristics on H7N9 virus and that future novel zoonotic avian viruses could emerge from non-zoonotic H7 viruses via acquisition of mutations that remove HA acid stability.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11495601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142511104","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
Features that matter: Evolutionary signatures can predict viral transmission routes. 重要的特征:进化特征可预测病毒传播路线
IF 5.5 1区 医学
PLoS Pathogens Pub Date : 2024-10-21 eCollection Date: 2024-10-01 DOI: 10.1371/journal.ppat.1012629
Maya Wardeh, Jack Pilgrim, Melody Hui, Aurelia Kotsiri, Matthew Baylis, Marcus S C Blagrove
{"title":"Features that matter: Evolutionary signatures can predict viral transmission routes.","authors":"Maya Wardeh, Jack Pilgrim, Melody Hui, Aurelia Kotsiri, Matthew Baylis, Marcus S C Blagrove","doi":"10.1371/journal.ppat.1012629","DOIUrl":"10.1371/journal.ppat.1012629","url":null,"abstract":"<p><p>Routes of virus transmission between hosts are key to understanding viral epidemiology. Different routes have large effects on viral ecology, and likelihood and rate of transmission; for example, respiratory and vector-borne viruses together encompass the majority of rapid outbreaks and high-consequence animal and plant epidemics. However, determining the specific transmission route(s) can take months to years, delaying mitigation efforts. Here, we identify the viral features and evolutionary signatures which are predictive of viral transmission routes and use them to predict potential routes for fully-sequenced viruses in silico and rapidly, for both viruses with no observed routes, as well as viruses with missing routes. This was achieved by compiling a dataset of 24,953 virus-host associations with 81 defined transmission routes, constructing a hierarchy of virus transmission encompassing those routes and 42 higher-order modes, and engineering 446 predictive features from three complementary perspectives. We integrated those data and features to train 98 independent ensembles of LightGBM classifiers. We found that all features contributed to the prediction for at least one of the routes and/or modes of transmission, demonstrating the utility of our broad multi-perspective approach. Our framework achieved ROC-AUC = 0.991, and F1-score = 0.855 across all included transmission routes and modes, and was able to achieve high levels of predictive performance for high-consequence respiratory (ROC-AUC = 0.990, and F1-score = 0.864) and vector-borne transmission (ROC-AUC = 0.997, and F1-score = 0.921). Our framework ranks the viral features in order of their contribution to prediction, per transmission route, and hence identifies the genomic evolutionary signatures associated with each route. Together with the more matured field of viral host-range prediction, our predictive framework could: provide early insights into the potential for, and pattern of viral spread; facilitate rapid response with appropriate measures; and significantly triage the time-consuming investigations to confirm the likely routes of transmission.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478575","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
Mlf mediates proteotoxic response via formation of cellular foci for protein folding and degradation in Giardia. Mlf 通过在贾第鞭毛虫体内形成用于蛋白质折叠和降解的细胞灶来介导蛋白质毒性反应。
IF 5.5 1区 医学
PLoS Pathogens Pub Date : 2024-10-21 eCollection Date: 2024-10-01 DOI: 10.1371/journal.ppat.1012617
Martina Vinopalová, Lenka Arbonová, Zoltán Füssy, Vít Dohnálek, Abdul Samad, Tomáš Bílý, Marie Vancová, Pavel Doležal
{"title":"Mlf mediates proteotoxic response via formation of cellular foci for protein folding and degradation in Giardia.","authors":"Martina Vinopalová, Lenka Arbonová, Zoltán Füssy, Vít Dohnálek, Abdul Samad, Tomáš Bílý, Marie Vancová, Pavel Doležal","doi":"10.1371/journal.ppat.1012617","DOIUrl":"10.1371/journal.ppat.1012617","url":null,"abstract":"<p><p>Myeloid leukemia factor 1 (Mlf1) was identified as a proto-oncoprotein that affects hematopoietic differentiation in humans. However, its cellular function remains elusive, spanning roles from cell cycle regulation to modulation of protein aggregate formation and participation in ciliogenesis. Given that structurally conserved homologs of Mlf1 can be found across the eukaryotic tree of life, we decided to characterize its cellular role underlying this phenotypic pleiotropy. Using a model of the unicellular eukaryote Giardia intestinalis, we demonstrate that its Mlf1 homolog (GiMlf) mainly localizes to two types of cytosolic foci: microtubular structures, where it interacts with Hsp40, and ubiquitin-rich, membraneless compartments, found adjacent to mitochondrion-related organelles known as mitosomes, containing the 26S proteasome regulatory subunit 4. Upon cellular stress, GiMlf either relocates to the affected compartment or disperses across the cytoplasm, subsequently accumulating into enlarged foci during the recovery phase. In vitro assays suggest that GiMlf can be recruited to membranes through its affinity for signaling phospholipids. Importantly, cytosolic foci diminish in the gimlf knockout strain, which exhibits extensive proteomic changes indicative of compromised proteostasis. Consistent with data from other cellular systems, we propose that Mlf acts in the response to proteotoxic stress by mediating the formation of function-specific foci for protein folding and degradation.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478581","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
Linkage-specific ubiquitin binding interfaces modulate the activity of the chlamydial deubiquitinase Cdu1 towards poly-ubiquitin substrates. 链接特异性泛素结合界面调节衣原体去泛素化酶 Cdu1 对多泛素底物的活性。
IF 5.5 1区 医学
PLoS Pathogens Pub Date : 2024-10-21 eCollection Date: 2024-10-01 DOI: 10.1371/journal.ppat.1012630
Jan Schlötzer, Alexander Schmalix, Sophie Hügelschäffer, Dominic Rieger, Florian Sauer, Mark D Tully, Thomas Rudel, Silke Wiesner, Caroline Kisker
{"title":"Linkage-specific ubiquitin binding interfaces modulate the activity of the chlamydial deubiquitinase Cdu1 towards poly-ubiquitin substrates.","authors":"Jan Schlötzer, Alexander Schmalix, Sophie Hügelschäffer, Dominic Rieger, Florian Sauer, Mark D Tully, Thomas Rudel, Silke Wiesner, Caroline Kisker","doi":"10.1371/journal.ppat.1012630","DOIUrl":"10.1371/journal.ppat.1012630","url":null,"abstract":"<p><p>The chlamydial deubiquitinase Cdu1 of the obligate intracellular human pathogenic bacterium Chlamydia trachomatis plays important roles in the maintenance of chlamydial infection. Despite the structural similarities shared with its homologue Cdu2, both DUBs display remarkable differences in their enzymatic activity towards poly-UB chain substrates. Whereas Cdu1 is highly active towards K48- and K63- poly-UB chains, Cdu2 activity is restricted mostly to mono-UB substrates. Here, we shed light on the molecular mechanisms of the differential activity and the substrate specificity of Cdu1 to better understand the cellular processes it is involved in, including infection-related events. We found that the strikingly elevated activity of Cdu1 relative to its paralogue Cdu2 can be attributed to an N-terminally extended α-helix, which has not been observed in Cdu2. Moreover, by employing isothermal titration calorimetry and nuclear magnetic resonance spectroscopy, we demonstrate the differential recognition of K48- and K63-linked poly-UB substrates by Cdu1. Whereas K63-linked poly-UB substrates appear to be recognized by Cdu1 with only two independent ubiquitin interaction sites, up to four different binding interfaces are present for K48-linked ubiquitin chains. Combined, our data suggest that Cdu1 possesses a poly-UB chain directed activity that may enable its function as a multipurpose DUB with a broad substrate specificity.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11527256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478580","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
Retraction: Pseudomonas aeruginosa-induced nociceptor activation increases susceptibility to infection. 撤回:铜绿假单胞菌诱导的痛觉感受器激活增加了感染的易感性。
IF 5.5 1区 医学
PLoS Pathogens Pub Date : 2024-10-18 eCollection Date: 2024-10-01 DOI: 10.1371/journal.ppat.1012646
{"title":"Retraction: Pseudomonas aeruginosa-induced nociceptor activation increases susceptibility to infection.","authors":"","doi":"10.1371/journal.ppat.1012646","DOIUrl":"https://doi.org/10.1371/journal.ppat.1012646","url":null,"abstract":"","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478585","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
Distinct mechanisms of type 3 secretion system recognition control LTB4 synthesis in neutrophils and macrophages. 3型分泌系统识别控制中性粒细胞和巨噬细胞中LTB4合成的不同机制
IF 5.5 1区 医学
PLoS Pathogens Pub Date : 2024-10-18 eCollection Date: 2024-10-01 DOI: 10.1371/journal.ppat.1012651
Amanda Brady, Leonardo C Mora Martinez, Benjamin Hammond, Kaitlyn M Whitefoot-Keliin, Bodduluri Haribabu, Silvia M Uriarte, Matthew B Lawrenz
{"title":"Distinct mechanisms of type 3 secretion system recognition control LTB4 synthesis in neutrophils and macrophages.","authors":"Amanda Brady, Leonardo C Mora Martinez, Benjamin Hammond, Kaitlyn M Whitefoot-Keliin, Bodduluri Haribabu, Silvia M Uriarte, Matthew B Lawrenz","doi":"10.1371/journal.ppat.1012651","DOIUrl":"10.1371/journal.ppat.1012651","url":null,"abstract":"<p><p>Leukotriene B4 (LTB4) is an inflammatory lipid produced in response to pathogens that is critical for initiating the inflammatory cascade needed to control infection. However, during plague, Yersinia pestis inhibits the timely synthesis of LTB4 and subsequent inflammation. Using bacterial mutants, we previously determined that Y. pestis inhibits LTB4 synthesis via the action of the Yop effector proteins that are directly secreted into host cells through a type 3 secretion system (T3SS). Here, we show that the T3SS is the primary pathogen associated molecular pattern (PAMP) required for production of LTB4 in response to both Yersinia and Salmonella. However, we also unexpectantly discovered that T3SS-mediated LTB4 synthesis by neutrophils and macrophages require the activation of two distinctly different host signaling pathways. We identified that phagocytosis and the NLRP3/CASP1 inflammasome significantly impact LTB4 synthesis by macrophages but not neutrophils. Instead, the SKAP2/PLC signaling pathway is required for T3SS-mediated LTB4 production by neutrophils. Finally, while recognition of the T3SS is required for LTB4 production, we also discovered that a second unrelated PAMP-mediated signal activates the MAP kinase pathway needed for synthesis. Together, these data demonstrate significant differences in the host factors and signaling pathways required by macrophages and neutrophils to quickly produce LTB4 in response to bacteria. Moreover, while macrophages and neutrophils might rely on different signaling pathways for T3SS-dependent LTB4 synthesis, Y. pestis has evolved virulence mechanisms to counteract this response by either leukocyte to inhibit LTB4 synthesis and colonize the host.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478573","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
Resistance to Cry14A family Bacillus thuringiensis crystal proteins in Caenornabditis elegans operates via the nhr-31 transcription factor and vacuolar-type ATPase pathway. 草履虫通过 nhr-31 转录因子和液泡型 ATPase 途径对 Cry14A 系列苏云金芽孢杆菌晶体蛋白产生抗性。
IF 5.5 1区 医学
PLoS Pathogens Pub Date : 2024-10-18 eCollection Date: 2024-10-01 DOI: 10.1371/journal.ppat.1012611
Youmie Kim, Thanh-Thanh Nguyen, Daniel J Durning, Takao Ishidate, Ozkan Aydemir, Craig C Mello, Yan Hu, Theodore W Kahn, Raffi V Aroian
{"title":"Resistance to Cry14A family Bacillus thuringiensis crystal proteins in Caenornabditis elegans operates via the nhr-31 transcription factor and vacuolar-type ATPase pathway.","authors":"Youmie Kim, Thanh-Thanh Nguyen, Daniel J Durning, Takao Ishidate, Ozkan Aydemir, Craig C Mello, Yan Hu, Theodore W Kahn, Raffi V Aroian","doi":"10.1371/journal.ppat.1012611","DOIUrl":"10.1371/journal.ppat.1012611","url":null,"abstract":"<p><p>Bacillus thuringiensis (Bt) has been successfully used commercially for more than 60 years for biocontrol of insect pests. Since 1996, transgenic plants expressing Bt crystal (Cry) proteins have been used commercially to provide protection against insects that predate on corn and cotton. More recently, Bt Cry proteins that target nematodes have been discovered. One of these, Cry14Ab, has been expressed in transgenic soybean plants and found to provide significant protection against the soybean cyst nematode, Heterodera glycines. However, to date there has been no description of high-level resistance to any Cry14A family protein in nematodes. Here, we describe forward genetic screens to identify such mutants using the nematode Caenorhabditis elegans. Although non-conditional screens failed to identify highly resistant C. elegans, a conditional (temperature-sensitive) genetic screen identified one mutant, bre-6(ye123) (for Bt protein resistant), highly resistant to both Cry14Aa and Cry14Ab. The mutant comes at a high fitness cost, showing significant delays in growth and development and reduced fecundity. bre-6(ye123) hermaphrodites are only weakly resistant to copper intoxication, indicating that the mutant is not highly resistant to all insults. Backcrossing-whole genome sequencing was used to identify the gene mutated in ye123 as the nuclear hormone receptor nhr-31. RNAi, DNA rescue, and CRISPR analyses confirm that resistance to Cry14Aa intoxication in bre-6(ye123) is due to mutation of nhr-31 and was renamed nhr-31(ye123). As predicted for a mutation in this gene, nhr-31(ye123) animals showed significantly reduced expression of most of the subunits of the C. elegans vacuolar ATPase (vATPase). Mutants in the vATPase subunits unc-32 and vha-7 also show resistance to Cry14Aa and/or Cry14Ab. These data demonstrate that nhr-31 and the vATPase play a significant role in the intoxication of C. elegans by Cry14A family proteins, that reduction in vATPase levels result in high resistance to Cry14A family proteins, and that such resistance comes at a high fitness cost. Based on the relative difficulty of finding resistant mutants and the fitness cost associated with the vATPase pathway, our data suggest that transgenic Cry14Ab plants may hold up well to resistance by nematode parasites.</p>","PeriodicalId":48999,"journal":{"name":"PLoS Pathogens","volume":null,"pages":null},"PeriodicalIF":5.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11524453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142478584","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
BglaTNB6, a tailocin produced by a plant-associated nonpathogenic bacterium, prevents rice seed-borne bacterial diseases. BglaTNB6是一种由植物相关非致病菌产生的尾孢菌素,可预防水稻种子传播的细菌性病害。
IF 5.5 1区 医学
PLoS Pathogens Pub Date : 2024-10-18 eCollection Date: 2024-10-01 DOI: 10.1371/journal.ppat.1012645
Yusuke Kouzai, Yoshiyuki Sagehashi, Riku Watanabe, Hideyuki Kajiwara, Nobuhiro Suzuki, Hiroshi Ono, Ken Naito, Chiharu Akimoto-Tomiyama
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