cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.13377014
title: A novel phosphoinositide kinase Fab1 regulates biosynthesis of pathogenic aflatoxin in <i>Aspergillus flavus</i>

description: <i>Aspergillus flavus</i> (<i>A. flavus</i>) is one of the most important model environmental fungi which can produce a potent toxin and carcinogen known as aflatoxin. Aflatoxin contamination causes massive agricultural economic loss and a critical human health issue each year. Although a functional vacuole has been highlighted for its fundamental importance in fungal virulence, the molecular mechanisms of the vacuole in regulating the virulence of <i>A. flavus</i> remain largely unknown. Here, we identified a novel vacuole-related protein in <i>A. flavus</i>, the ortholog of phosphatidylinositol-3-phosphate-5-kinase (Fab1) in <i>Saccharomyces cerevisiae</i>. This kinase was located at the vacuolar membrane, and loss of <i>fab1</i> function was found to affect the growth, conidia and sclerotial development, cellular acidification and metal ion homeostasis, aflatoxin production and pathogenicity of <i>A. flavus</i>. Further functional analysis revealed that Fab1 was required to maintain the vacuole size and cell morphology. Additional quantitative proteomic analysis suggested that Fab1 was likely to play an important role in maintaining vacuolar/cellular homeostasis, with vacuolar dysregulation upon <i>fab1</i> deletion leading to impaired aflatoxin synthesis in this fungus. Together, these results provide insight into the molecular mechanisms by which this pathogen produces aflatoxin and mediates its pathogenicity, and may facilitate dissection of the vacuole-mediated regulatory network in <i>A. flavus</i>.
DOI: 10.6084/m9.figshare.16415536
title: S-adenosyl-L-homocysteine hydrolase FgSah1 is required for fungal development and virulence in <i>Fusarium graminearum</i>

description: The S-adenosyl-L-homocysteine hydrolase (Sah1) plays a crucial role in methylation and lipid metabolism in yeast and mammals, yet its function remains elusive in filamentous fungi. In this study, we characterized Sah1 in the phytopathogenic fungus <i>F. graminearum</i> by generating knockout and knockout-complemented strains of <i>FgSAH1</i>. We found that the FgSah1-GFP fusion protein was localized to the cytoplasm, and that deletion of <i>FgSAH1</i> resulted in defects in vegetative growth, asexual and sexual reproduction, stress responses, virulence, lipid metabolism, and tolerance against fungicides. Moreover, the accumulations of S-adenosyl-L-homocysteine (AdoHcy) and S-adenosyl-L-methionine (AdoMet) (the methyl group donor in most methyl transfer reactions) in Δ<i>FgSah1</i> were seven- and ninefold higher than those in the wild-type strain, respectively. All of these defective phenotypes in Δ<i>FgSah1</i> mutants were rescued by target gene complementation. Taken together, these results demonstrate that <i>FgSah1</i> plays essential roles in methylation metabolism, fungal development, full virulence, multiple stress responses, lipid metabolism, and fungicide sensitivity in <i>F. graminearum</i>. To our knowledge, this is the first report on the systematic functional characterization of Sah1 in <i>F. graminearum</i>.
DOI: 10.6084/m9.figshare.14617748.v1
title: A phage protein-derived antipathogenic peptide that targets type IV pilus assembly

description: Phage-inspired antibacterial discovery is a new approach that recruits phages in search for antibacterials with new molecular targets, in that phages are the biological entities well adapted to hijack host bacterial physiology in favor of their own thrive. We previously observed that phage-mediated twitching motility inhibition was effective to control the acute infections caused by <i>Pseudomonas aeruginosa</i> and that the motility inhibition was attributed to the delocalization of PilB, the type IV pilus (TFP) assembly ATPase by binding of the 136-amino acid (aa) phage protein, Tip. Here, we created a series of truncated and point-mutant Tip proteins to identify the critical residues in the Tip bioactivity: N-terminal 80-aa residues were dispensable for the Tip activity; we identified that Asp82, Leu84, and Arg85 are crucial in the Tip function. Furthermore, a synthetic 15-aa peptide (P1) that corresponds to Leu73 to Ala87 is shown to suffice for PilB delocalization, twitching inhibition, and virulence attenuation upon exogenous administration. The transgenic flies expressing the 15-aa peptide were resistant to <i>P. aeruginosa</i> infections as well. Taken together, this proof-of-concept study reveals a new antipathogenic peptide hit targeting bacterial motility and provides an insight into antibacterial discovery targeting TFP assembly.
DOI: 10.6084/m9.figshare.15111819
title: A novel transcription factor UvCGBP1 regulates development and virulence of rice false smut fungus <i>Ustilaginoidea virens</i>

description: <i>Ustilaginoidea virens</i>, causing rice false smut (RFS) is an economically important ascomycetous fungal pathogen distributed in rice-growing regions worldwide. Here, we identified a novel transcription factor UvCGBP1 (Cutinase G-box binding protein) from this fungus, which is unique to ascomycetes. Deletion of <i>UvCGBP1</i> affected development and virulence of <i>U. virens</i>. A total of 865 downstream target genes of UvCGBP1 was identified using ChIP-seq and the most significant KEGG enriched functional pathway was the MAPK signaling pathway. Approximately 36% of target genes contain the AGGGG (G-box) motif in their promoter. Among the targets, deletion of <i>UvCGBP1</i> affected transcriptional and translational levels of <i>UvPmk1</i> and <i>UvSlt2</i>, both of which were important in virulence. ChIP-qPCR, yeast one-hybrid and EMSA confirmed that UvCGBP1 can bind the promoter of <i>UvPmk1</i> or <i>UvSlt2</i>. Overexpression of <i>UvPmk1</i> in the <i>∆UvCGBP1-33</i> mutant restored partially its virulence and hyphae growth, indicating that UvCGBP1 could function via the MAPK pathway to regulate fungal virulence. Taken together, this study uncovered a novel regulatory mechanism of fungal virulence linking the MAPK pathway mediated by a G-box binding transcription factor, UvCGBP1.
DOI: 10.6084/m9.figshare.16699099.v1
title: Deciphering of <i>Candida parapsilosis</i> induced immune response in <i>Drosophila melanogaster</i>

description: <i>Candida</i> infections are the most prevalent cause of serious human mycoses and are the third most common pathogens isolated from bloodstream infections in hospitalized patients. <i>C. parapsilosis</i> is a member of the <i>non-albicans</i> spp., which have a predilection for causing life-threatening disease in neonates and hospitalized pediatric patients. In this study, we utilized a <i>Drosophila melanogaster</i> infection model to analyze the immunological responses to <i>C. parapsilosis</i>. Our results demonstrate that the Toll pathway in <i>Drosophila</i> controls <i>C. parapsilosis</i> proliferation as the Toll signaling mutant <i>MyD88<sup>−/</sup></i><sup>−</sup> flies are highly susceptible to <i>C. parapsilosis</i>. We also confirmed that the <i>MyD88<sup>−/</sup></i><sup>−</sup> fly is a convenient invertebrate animal model to analyze virulence properties of different species and strains from the <i>C. parapsilosis sensu lato</i> complex as <i>C. orthopsilosis, C. metapsilosis</i> proved to be less virulent than <i>C. parapsilosis sensu stricto</i> and the <i>N</i>-mannan deficient <i>C. parapsilosis och1</i>Δ/Δ strain showed attenuated pathogenicity in this immunodeficient <i>Drosophila</i> background. We also found that Persephone protease is not required for detection and activation of Toll pathway during <i>C. parapsilosis</i> infection. Furthermore, we observed that <i>Drosophila</i> β-glucan receptor deficient flies where more sensitive to <i>C. parapsilosis</i> compared to wild-type flies; however, we could not find a clear dependence on the recognition of this receptor and the cell wall β-glucan exposure-induced host response. These studies establish this <i>D. melanogaster</i> infection model as an efficient tool in deciphering immune responses to <i>C. parapsilosis</i> as well as for assessing virulence factors produced by this emerging fungal predator.
DOI: 10.6084/m9.figshare.25245997
title: Code for processing and analyzing proteome turnover data generated via dSILO

description: <b>Code to calculate half-lives from MaxQuant output files, filter data, and generate figures</b>Includes:R code for generating half-lives and heatmaps using PSM values from a MaxQuant-derived evidence.txt file (<i>related to Figure 2, Figure 3, and SF1</i>)<br>Python scripts to filter data by RSQ and PSM counts (<i>related to Figure 2G, Figure 3</i>)<br>Python scripts to assign proteins to complexes via CORUM, perform KS testing, plot distributions, and map half-lives onto a cryo-EM structure of the respirasome (<i>related to Figure 4 and SF4</i>)<br><br>and all associated input/output files.<br>
DOI: 10.6084/m9.figshare.16586946.v3
title: The ApoA-I mimetic peptide 4F attenuates in vitro replication of SARS-CoV-2, associated apoptosis, oxidative stress and inflammation in epithelial cells

description: An oral antiviral against SARS-CoV-2 that also attenuates inflammatory instigators of severe COVID-19 is not available to date. Herein, we show that the apoA-I mimetic peptide 4 F inhibits Spike mediated viral entry and has antiviral activity against SARS-CoV-2 in human lung epithelial Calu3 and Vero-E6 cells. In SARS-CoV-2 infected Calu3 cells, 4 F upregulated inducers of the interferon pathway such as MX-1 and Heme oxygenase 1 (HO-1) and downregulated mitochondrial reactive oxygen species (mito-ROS) and CD147, a host protein that mediates viral entry. 4 F also reduced associated cellular apoptosis and secretion of IL-6 in both SARS-CoV-2 infected Vero-E6 and Calu3 cells. Thus, 4 F attenuates <i>in vitro</i> SARS-CoV-2 replication, associated apoptosis in epithelial cells and secretion of IL-6, a major cytokine related to COVID-19 morbidity. Given established safety of 4 F in humans, clinical studies are warranted to establish 4 F as therapy for COVID-19.
DOI: 10.6084/m9.figshare.15112213.v2
title: <i>Trypanosoma evansi</i> evades host innate immunity by releasing extracellular vesicles to activate TLR2-AKT signaling pathway

description: Surra, one of the most important animal diseases with economic consequences in Asia and South America, is caused by <i>Trypanosoma evansi</i>. However, the mechanism of immune evasion by <i>T. evansi</i> has not been extensively studied. In the present study, <i>T. evansi</i> extracellular vesicles (TeEVs) were characterized and the role of TeEVs in <i>T. evansi</i> infection were examined. The results showed that <i>T. evansi</i> and TeEVs could activate TLR2-AKT pathway to inhibit the secretions of IL-12p40, IL-6, and TNF-α in mouse BMDMs. TLR2<sup>−/-</sup> mice and mice with a blocked AKT pathway were more resistant to <i>T. evansi</i> infection than wild type (WT) mice, with a significantly lower infection rate, longer survival time and less parasite load, as well as an increased secretion level of IL-12p40 and IFN-γ. Kinetoplastid membrane protein-11 (KMP-11) of TeEVs could activate AKT pathway and inhibit the productions of IL-12p40, TNF-α, and IL-6 <i>in vitro</i>. TeEVs and KMP-11 could inhibit the productions of IL-12p40 and IFN-γ, promote <i>T. evansi</i> proliferation and shorten the survival time of infected mice <i>in vivo</i>. In conclusion, <i>T. evansi</i> could escape host immune response through inhibiting the productions of inflammatory cytokines via secreting TeEVs to activate TLR2-AKT pathway. KMP-11 in TeEVs was involved in promoting <i>T. evansi</i> infection. Extracellular vesicles (EVs) secreted by <i>Trypanosoma evansi</i> (<i>T. evansi</i>) activate the TLR2-AKT signaling pathway to inhibit the production of inflammatory cytokines, thereby escaping the host’s immune response. Kinetoplastid membrane protein-11 (KMP-11) in EVs is related to the promotion of <i>T.</i> infection via AKT pathway.
DOI: 10.6084/m9.figshare.16611534
title: A clubroot pathogen effector targets cruciferous cysteine proteases to suppress plant immunity

description: Plant pathogen effector proteins are key to pathogen virulence. In susceptible host Brassicas, the clubroot pathogen, <i>Plasmodiophora brassicae</i>, induces the production of nutrient-sink root galls, at the site of infection. Among a list of 32 <i>P. brassiae</i> effector candidates previously reported by our group, we identified SSPbP53 as a putative apoplastic cystatin-like protein highly expressed during the secondary infection. Here we found that SSPbP53 encoding gene is conserved among several <i>P. brassicae</i> pathotypes and that SSPbP53 is an apoplastic protein able to directly interact with and inhibit cruciferous papain-like cysteine proteases (PLCPs), specifically Arabidopsis XYLEM CYSTEINE PEPTIDASE 1 (<i>At</i>XCP1). The severity of clubroot disease is greatly reduced in the Arabidopsis <i>xcp1</i> null mutant (<i>At</i>Δ<i>xcp1</i>) after infection with <i>P. brassicae</i> resting spores, indicating that the interaction of <i>P. brassicae</i> SSPbP53 with XCP1 is important to clubroot susceptibility. SSPbP53 is the first cystatin-like effector identified and characterized for a plant pathogenic protist.
DOI: 10.6084/m9.figshare.17695938
title: Unique virulence role of post-translocational chaperone PrsA in shaping <i>Streptococcus pyogenes</i> secretome

description: <i>Streptococcus pyogenes</i> (group A <i>Streptococcus</i>, GAS) is a strict human pathogen causing a broad spectrum of diseases and a variety of autoimmune sequelae. The pathogenesis of GAS infection mostly relies on the production of an extensive network of cell wall-associated and secreted virulence proteins, such as adhesins, toxins, and exoenzymes. PrsA, the only extracellular parvulin-type peptidyl-prolyl isomerase expressed ubiquitously in Gram-positive bacteria, has been suggested to assist the folding and maturation of newly exported proteins to acquire their native conformation and activity. Two PrsA proteins, PrsA1 and PrsA2, have been identified in GAS, but the respective contribution of each PrsA in GAS pathogenesis remains largely unknown. By combining comparative proteomic and phenotypic analysis approaches, we demonstrate that both PrsA isoforms are required to maintain GAS proteome homeostasis and virulence-associated traits in a unique and overlapping manner. The inactivation of both PrsA in GAS caused remarkable impairment in biofilm formation, host adherence, infection-induced cytotoxicity, and <i>in vivo</i> virulence in a murine soft tissue infection model. The concordance of proteomic and phenotypic data clearly features the essential role of PrsA in GAS full virulence.
DOI: 10.6084/m9.figshare.17695938.v1
title: Unique virulence role of post-translocational chaperone PrsA in shaping <i>Streptococcus pyogenes</i> secretome

description: <i>Streptococcus pyogenes</i> (group A <i>Streptococcus</i>, GAS) is a strict human pathogen causing a broad spectrum of diseases and a variety of autoimmune sequelae. The pathogenesis of GAS infection mostly relies on the production of an extensive network of cell wall-associated and secreted virulence proteins, such as adhesins, toxins, and exoenzymes. PrsA, the only extracellular parvulin-type peptidyl-prolyl isomerase expressed ubiquitously in Gram-positive bacteria, has been suggested to assist the folding and maturation of newly exported proteins to acquire their native conformation and activity. Two PrsA proteins, PrsA1 and PrsA2, have been identified in GAS, but the respective contribution of each PrsA in GAS pathogenesis remains largely unknown. By combining comparative proteomic and phenotypic analysis approaches, we demonstrate that both PrsA isoforms are required to maintain GAS proteome homeostasis and virulence-associated traits in a unique and overlapping manner. The inactivation of both PrsA in GAS caused remarkable impairment in biofilm formation, host adherence, infection-induced cytotoxicity, and <i>in vivo</i> virulence in a murine soft tissue infection model. The concordance of proteomic and phenotypic data clearly features the essential role of PrsA in GAS full virulence.
DOI: 10.5517/cc11d0yd
title: CCDC 964873: Experimental Crystal Structure Determination

description: Related Article: Zhi-Feng Ma, Ying-Hui Zhang, Tong-Liang Hu, Xian-He Bu|2014|Wuji Huaxue Xuebao|30|204|
description: An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
DOI: 10.5517/cc11d11j
title: CCDC 964876: Experimental Crystal Structure Determination

description: Related Article: Zhi-Feng Ma, Ying-Hui Zhang, Tong-Liang Hu, Xian-He Bu|2014|Wuji Huaxue Xuebao|30|204|
description: An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
DOI: 10.5517/cc11p394
title: CCDC 973595: Experimental Crystal Structure Determination

description: Related Article: M.S.Dronova, A.N.Bilyachenko, A.A.Korlyukov, D.E.Arkhipov, A.D.Kirilin, E.S.Shubina, G.M.Babakhina, M.M.Levitsky|2013|Izv.Akad.Nauk SSSR,Ser.Khim.||1941|
description: An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
DOI: 10.5517/ccdc.csd.cc2hgtld
title: CCDC 2308154: Experimental Crystal Structure Determination

description: Related Article: Gary C. George III, Mahshad Karimi, Navkiran Juneja, Daniel K. Unruh, Ryan H. Groeneman, Kristin M. Hutchins|2024|Cryst.Growth Des.|24|2468|doi:10.1021/acs.cgd.3c01435
description: An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
DOI: 10.5517/ccdc.csd.cc2hgtmf
title: CCDC 2308155: Experimental Crystal Structure Determination

description: Related Article: Gary C. George III, Mahshad Karimi, Navkiran Juneja, Daniel K. Unruh, Ryan H. Groeneman, Kristin M. Hutchins|2024|Cryst.Growth Des.|24|2468|doi:10.1021/acs.cgd.3c01435
description: An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
DOI: 10.5517/ccdc.csd.cc2hgtng
title: CCDC 2308156: Experimental Crystal Structure Determination

description: Related Article: Gary C. George III, Mahshad Karimi, Navkiran Juneja, Daniel K. Unruh, Ryan H. Groeneman, Kristin M. Hutchins|2024|Cryst.Growth Des.|24|2468|doi:10.1021/acs.cgd.3c01435
description: An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
DOI: 10.5517/ccdc.csd.cc2hgtph
title: CCDC 2308157: Experimental Crystal Structure Determination

description: Related Article: Gary C. George III, Mahshad Karimi, Navkiran Juneja, Daniel K. Unruh, Ryan H. Groeneman, Kristin M. Hutchins|2024|Cryst.Growth Des.|24|2468|doi:10.1021/acs.cgd.3c01435
description: An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
DOI: 10.5517/ccdc.csd.cc2hgtqj
title: CCDC 2308158: Experimental Crystal Structure Determination

description: Related Article: Gary C. George III, Mahshad Karimi, Navkiran Juneja, Daniel K. Unruh, Ryan H. Groeneman, Kristin M. Hutchins|2024|Cryst.Growth Des.|24|2468|doi:10.1021/acs.cgd.3c01435
description: An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
DOI: 10.6084/m9.figshare.13713068.v2
title: The transcription factor Ndt80 is a repressor of <i>Candida parapsilosis</i> virulence attributes

description: <i>Candida parapsilosis</i> is an emergent opportunistic yeast among hospital settings that affects mainly neonates and immunocompromised patients. Its most remarkable virulence traits are the ability to adhere to prosthetic materials, as well as the formation of biofilm on abiotic surfaces. The Ndt80 transcription factor was identified as one of the regulators of biofilm formation by <i>C. parapsilosis</i>; however, its function in this process was not yet clarified. By knocking out <i>NDT80</i> (<i>CPAR2-213640</i>) gene, or even just one single copy of the gene, we observed substantial alterations of virulence attributes, including morphogenetic changes, adhesion and biofilm growth profiles. Both <i>ndt80Δ</i> and <i>ndt80ΔΔ</i> mutants changed colony and cell morphologies from smooth, yeast-shaped to crepe and pseudohyphal elongated forms, exhibiting promoted adherence to polystyrene microspheres and notably, forming a higher amount of biofilm compared to wild-type strain. Interestingly, we identified transcription factors Ume6, Cph2, Cwh41, Ace2, Bcr1, protein kinase Mkc1 and adhesin Als7 to be under Ndt80 negative regulation, partially explaining the phenotypes displayed by the <i>ndt80ΔΔ</i> mutant. Furthermore, <i>ndt80ΔΔ</i> pseudohyphae adhered more rapidly and were more resistant to murine macrophage attack, becoming deleterious to such cells after phagocytosis. Unexpectedly, our findings provide the first evidence for a direct role of Ndt80 as a repressor of <i>C. parapsilosis</i> virulence attributes. This finding shows that <i>C. parapsilosis</i> Ndt80 functionally diverges from its homolog in the close related fungal pathogen <i>C. albicans</i>.
DOI: 10.5517/ccdc.csd.cc2hgtrk
title: CCDC 2308159: Experimental Crystal Structure Determination

description: Related Article: Gary C. George III, Mahshad Karimi, Navkiran Juneja, Daniel K. Unruh, Ryan H. Groeneman, Kristin M. Hutchins|2024|Cryst.Growth Des.|24|2468|doi:10.1021/acs.cgd.3c01435
description: An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.