cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.13078725.v4
title: Proteome analysis of bronchoalveolar lavage fluids reveals host and fungal proteins highly expressed during invasive pulmonary aspergillosis in mice and humans

description: Invasive pulmonary aspergillosis (IPA) is a severe infection that is difficult to diagnose due to the ubiquitous presence of fungal spores, the underlying diseases of risk patients, and limitations of currently available markers. In this study, we performed a comprehensive liquid chromatography tandem mass spectrometry (LC-MS/MS)-based identification of host and fungal proteins expressed during IPA in mice and humans. The proteomic analysis of bronchoalveolar lavage samples of individual IPA and control cases allowed the description of common host factors that had significantly increased abundance in both infected animals and IPA patients compared to their controls. Although increased levels of these individual host proteins might not be sufficient to distinguish bacterial from fungal infection, a combination of these markers might be beneficial to improve diagnosis. We also identified 16 fungal proteins that were specifically detected during infection and may be valuable candidates for biomarker evaluation.
DOI: 10.5281/zenodo.4705287
title: Simulation output: Understanding wind-driven melt of patchy snow cover

description: This is the simulation output and exemplary files to initiate the simulation used in the manuscript <em><strong>Understanding wind-driven snowmelt of patchy snow cover</strong> </em>by Luuk van der Valk, Adriaan J. Teuling, Luc Girod, Norbert Pirk, Robin Stoffer and Chiel van Heerwaarden, The Cryosphere, submitted The subfolders contain the output per simulation, of which the names indicate the variable and the 2D crossection. The file called ..._default_0001800.nc contains the simulation statistics. The files in the main folder are the initialization file, the input file and the script used to generate the surface temperatures. Within these scripts, it is indicated which values are used for each simulation, with the current values being used for the P15M simulation. For more information, see the manuscript and https://microhh.readthedocs.io/en/latest/
DOI: 10.6084/m9.figshare.12852066.v3
title: A DUF4148 family protein produced inside RAW264.7 cells is a critical Burkholderia pseudomallei virulence factor

description: Burkholderia pseudomallei: is the etiological agent of the disease melioidosis and is a Tier 1 select agent. It survives and replicates inside phagocytic cells by escaping from the endocytic vacuole, replicating in the cytosol, spreading to other cells via actin polymerization and promoting the fusion of infected and uninfected host cells to form multinucleated giant cells. In this study, we utilized a proteomics approach to identify bacterial proteins produced inside RAW264.7 murine macrophages and host proteins produced in response to <i>B. pseudomallei</i> infection. Cells infected with <i>B. pseudomallei</i> strain K96243 were lysed and the lysate proteins digested and analyzed using nanoflow reversed-phase liquid chromatography and tandem mass spectrometry. Approximately 160 bacterial proteins were identified in the infected macrophages, including BimA, TssA, TssB, Hcp1 and TssM. Several previously uncharacterized <i>B. pseudomallei</i> proteins were also identified, including BPSS1996 and BPSL2748. Mutations were constructed in the genes encoding these novel proteins and their relative virulence was assessed in BALB/c mice. The 50% lethal dose for the <i>BPSS1996</i> mutant was approximately 55-fold higher than that of the wild type, suggesting that BPSS1996 is required for full virulence. Sera from <i>B. pseudomallei</i>-infected animals reacted with BPSS1996 and it was found to localize to the bacterial surface using indirect immunofluorescence. Finally, we identified 274 host proteins that were exclusively present or absent in infected RAW264.7 cells, including chemokines and cytokines involved in controlling the initial stages of infection.
DOI: 10.6084/m9.figshare.13053349
title: Exploring metal availability in the natural niche of <i>Streptococcus pneumoniae</i> to discover potential vaccine antigens

description: Nasopharyngeal colonization by <i>Streptococcus pneumoniae</i> is a prerequisite for pneumococcal transmission and disease. Current vaccines protect only against disease and colonization caused by a limited number of serotypes, consequently allowing serotype replacement and transmission. Therefore, the development of a broadly protective vaccine against colonization, transmission and disease is desired but requires a better understanding of pneumococcal adaptation to its natural niche. Hence, we measured the levels of free and protein-bound transition metals in human nasal fluid, to determine the effect of metal concentrations on the growth and proteome of <i>S. pneumoniae</i>. Pneumococci cultured in medium containing metal levels comparable to nasal fluid showed a highly distinct proteomic profile compared to standard culture conditions, including the increased abundance of nine conserved, putative surface-exposed proteins. AliA, an oligopeptide binding protein, was identified as the strongest protective antigen, demonstrated by the significantly reduced bacterial load in a murine colonization and a lethal mouse pneumonia model, highlighting its potential as vaccine antigen.
DOI: 10.6084/m9.figshare.12852066
title: A DUF4148 family protein produced inside RAW264.7 cells is a critical Burkholderia pseudomallei virulence factor

description: Burkholderia pseudomallei: is the etiological agent of the disease melioidosis and is a Tier 1 select agent. It survives and replicates inside phagocytic cells by escaping from the endocytic vacuole, replicating in the cytosol, spreading to other cells via actin polymerization and promoting the fusion of infected and uninfected host cells to form multinucleated giant cells. In this study, we utilized a proteomics approach to identify bacterial proteins produced inside RAW264.7 murine macrophages and host proteins produced in response to <i>B. pseudomallei</i> infection. Cells infected with <i>B. pseudomallei</i> strain K96243 were lysed and the lysate proteins digested and analyzed using nanoflow reversed-phase liquid chromatography and tandem mass spectrometry. Approximately 160 bacterial proteins were identified in the infected macrophages, including BimA, TssA, TssB, Hcp1 and TssM. Several previously uncharacterized <i>B. pseudomallei</i> proteins were also identified, including BPSS1996 and BPSL2748. Mutations were constructed in the genes encoding these novel proteins and their relative virulence was assessed in BALB/c mice. The 50% lethal dose for the <i>BPSS1996</i> mutant was approximately 55-fold higher than that of the wild type, suggesting that BPSS1996 is required for full virulence. Sera from <i>B. pseudomallei</i>-infected animals reacted with BPSS1996 and it was found to localize to the bacterial surface using indirect immunofluorescence. Finally, we identified 274 host proteins that were exclusively present or absent in infected RAW264.7 cells, including chemokines and cytokines involved in controlling the initial stages of infection.
DOI: 10.6084/m9.figshare.12852066.v2
title: A DUF4148 family protein produced inside RAW264.7 cells is a critical Burkholderia pseudomallei virulence factor

description: Burkholderia pseudomallei: is the etiological agent of the disease melioidosis and is a Tier 1 select agent. It survives and replicates inside phagocytic cells by escaping from the endocytic vacuole, replicating in the cytosol, spreading to other cells via actin polymerization and promoting the fusion of infected and uninfected host cells to form multinucleated giant cells. In this study, we utilized a proteomics approach to identify bacterial proteins produced inside RAW264.7 murine macrophages and host proteins produced in response to <i>B. pseudomallei</i> infection. Cells infected with <i>B. pseudomallei</i> strain K96243 were lysed and the lysate proteins digested and analyzed using nanoflow reversed-phase liquid chromatography and tandem mass spectrometry. Approximately 160 bacterial proteins were identified in the infected macrophages, including BimA, TssA, TssB, Hcp1 and TssM. Several previously uncharacterized <i>B. pseudomallei</i> proteins were also identified, including BPSS1996 and BPSL2748. Mutations were constructed in the genes encoding these novel proteins and their relative virulence was assessed in BALB/c mice. The 50% lethal dose for the <i>BPSS1996</i> mutant was approximately 55-fold higher than that of the wild type, suggesting that BPSS1996 is required for full virulence. Sera from <i>B. pseudomallei</i>-infected animals reacted with BPSS1996 and it was found to localize to the bacterial surface using indirect immunofluorescence. Finally, we identified 274 host proteins that were exclusively present or absent in infected RAW264.7 cells, including chemokines and cytokines involved in controlling the initial stages of infection.
DOI: 10.6084/m9.figshare.13053349.v4
title: Exploring metal availability in the natural niche of <i>Streptococcus pneumoniae</i> to discover potential vaccine antigens

description: Nasopharyngeal colonization by <i>Streptococcus pneumoniae</i> is a prerequisite for pneumococcal transmission and disease. Current vaccines protect only against disease and colonization caused by a limited number of serotypes, consequently allowing serotype replacement and transmission. Therefore, the development of a broadly protective vaccine against colonization, transmission and disease is desired but requires a better understanding of pneumococcal adaptation to its natural niche. Hence, we measured the levels of free and protein-bound transition metals in human nasal fluid, to determine the effect of metal concentrations on the growth and proteome of <i>S. pneumoniae</i>. Pneumococci cultured in medium containing metal levels comparable to nasal fluid showed a highly distinct proteomic profile compared to standard culture conditions, including the increased abundance of nine conserved, putative surface-exposed proteins. AliA, an oligopeptide binding protein, was identified as the strongest protective antigen, demonstrated by the significantly reduced bacterial load in a murine colonization and a lethal mouse pneumonia model, highlighting its potential as vaccine antigen.
DOI: 10.6084/m9.figshare.13053349.v3
title: Exploring metal availability in the natural niche of <i>Streptococcus pneumoniae</i> to discover potential vaccine antigens

description: Nasopharyngeal colonization by <i>Streptococcus pneumoniae</i> is a prerequisite for pneumococcal transmission and disease. Current vaccines protect only against disease and colonization caused by a limited number of serotypes, consequently allowing serotype replacement and transmission. Therefore, the development of a broadly protective vaccine against colonization, transmission and disease is desired but requires a better understanding of pneumococcal adaptation to its natural niche. Hence, we measured the levels of free and protein-bound transition metals in human nasal fluid, to determine the effect of metal concentrations on the growth and proteome of <i>S. pneumoniae</i>. Pneumococci cultured in medium containing metal levels comparable to nasal fluid showed a highly distinct proteomic profile compared to standard culture conditions, including the increased abundance of nine conserved, putative surface-exposed proteins. AliA, an oligopeptide binding protein, was identified as the strongest protective antigen, demonstrated by the significantly reduced bacterial load in a murine colonization and a lethal mouse pneumonia model, highlighting its potential as vaccine antigen.
DOI: 10.6084/m9.figshare.12344432.v3
title: UvrY is required for the full virulence of <i>Aeromonas dhakensis</i>

description: <i>Aeromonas dhakensis</i> is an emerging human pathogen which causes fast and severe infections worldwide. Under the gradual pressure of lacking useful antibiotics, finding a new strategy against <i>A. dhakensis</i> infection is urgent. To understand its pathogenesis, we created an <i>A. dhakensis</i> AAK1 mini-Tn10 transposon library to study the mechanism of <i>A. dhakensis</i> infection. By using a <i>Caenorhabditis elegans</i> model, we established a screening platform for the purpose of identifying attenuated mutants. The <i>uvrY</i> mutant, which conferred the most attenuated toxicity toward <i>C. elegans</i>, was identified. The <i>uvrY</i> mutant was also less virulent in C2C12 fibroblast and mice models, in line with <i>in vitro</i> results. To further elucidate the mechanism of UvrY in controlling the toxicity in <i>A. dhakensis</i>, we conducted a transcriptomic analysis. The RNAseq results showed that the expression of a unique hemolysin <i>ahh1</i> and other virulence factors were regulated by UvrY. Complementation of Ahh1, one of the most important virulence factors, rescued the pore-formation phenotype of <i>uvrY</i> mutant in <i>C. elegans</i>; however, complementation of <i>ahh1</i> endogenous promoter-driven <i>ahh1</i> could not produce Ahh1 and rescue the virulence in the <i>uvrY</i> mutant. These findings suggest that UvrY is required for the expression of Ahh1 in <i>A. dhakensis</i>. Taken together, our results suggested that UvrY controls several different virulence factors and is required for the full virulence of <i>A. dhakensis</i>. The two-component regulator UvrY therefore a potential therapeutic target which is worthy of further study.
DOI: 10.6084/m9.figshare.12852045.v3
title: Transcriptional remodeling during metacyclogenesis in <i>Trypanosoma cruzi</i> I

description: Metacyclogenesis is one of the most important processes in the life cycle of <i>Trypanosoma cruzi</i>. In this stage, noninfective epimastigotes become infective metacyclic trypomastigotes. However, the transcriptomic changes that occur during this transformation remain uncertain. Illumina RNA-sequencing of epimastigotes and metacyclic trypomastigotes belonging to <i>T. cruzi</i> DTU I was undertaken. Sequencing reads were aligned and mapped against the reference genome, differentially expressed genes between the two life cycle stages were identified, and metabolic pathways were reconstructed. Gene expression differed significantly between epimastigotes and metacyclic trypomastigotes. The cellular pathways that were mostly downregulated during metacyclogenesis involved glucose energy metabolism (glycolysis, pyruvate metabolism, the Krebs cycle, and oxidative phosphorylation), amino acid metabolism, and DNA replication. By contrast, the processes where an increase in gene expression was observed included those related to autophagy (particularly Atg7 and Atg8 transcripts), corroborating its importance during metacyclogenesis, endocytosis, by an increase in the expression of the AP-2 complex subunit alpha, protein processing in the endoplasmic reticulum and meiosis. Study findings indicate that in <i>T. cruzi</i> metacyclic trypomastigotes, metabolic processes are decreased, and expression of genes involved in specific cell cycle processes is increased to facilitate transformation to this infective stage.
DOI: 10.6084/m9.figshare.12319646.v4
title: Identification of conditionally essential genes for <i>Streptococcus suis</i> infection in pigs

description: <b>Streptococcus suis</b> is a Gram-positive bacterium and zoonotic pathogen that causes meningitis and sepsis in pigs and humans. The aim of this study was to identify genes required for <i>S. suis</i> infection. We created Tn-Seq libraries in a virulent <i>S. suis</i> strain 10, which was used to inoculate pigs in an intrathecal experimental infection. Comparative analysis of the relative abundance of mutants recovered from different sites of infection (blood, cerebrospinal fluid, and meninges of the brain) identified 361 conditionally essential genes, i.e. required for infection, which is about 18% of the genome. The conditionally essential genes were primarily involved in metabolic and transport processes, regulation, ribosomal structure and biogenesis, transcription, and cell wall membrane and envelope biogenesis, stress defenses, and immune evasion. Directed mutants were created in a set of 10 genes of different genetic ontologies and their role was determined in <i>ex vivo</i> models. Mutants showed different levels of sensitivity to survival in whole blood, serum, cerebrospinal fluid, thermic shock, and stress conditions, as compared to the wild type. Additionally, the role of three selected mutants was validated in co-infection experiments in which pigs were infected with both wild type and isogenic mutant strains. The genetic determinants of infection identified in this work contribute to novel insights in <i>S. suis</i> pathogenesis and could serve as targets for novel vaccines or antimicrobial drugs.
DOI: 10.6084/m9.figshare.12344432
title: UvrY is required for the full virulence of <i>Aeromonas dhakensis</i>

description: <i>Aeromonas dhakensis</i> is an emerging human pathogen which causes fast and severe infections worldwide. Under the gradual pressure of lacking useful antibiotics, finding a new strategy against <i>A. dhakensis</i> infection is urgent. To understand its pathogenesis, we created an <i>A. dhakensis</i> AAK1 mini-Tn10 transposon library to study the mechanism of <i>A. dhakensis</i> infection. By using a <i>Caenorhabditis elegans</i> model, we established a screening platform for the purpose of identifying attenuated mutants. The <i>uvrY</i> mutant, which conferred the most attenuated toxicity toward <i>C. elegans</i>, was identified. The <i>uvrY</i> mutant was also less virulent in C2C12 fibroblast and mice models, in line with <i>in vitro</i> results. To further elucidate the mechanism of UvrY in controlling the toxicity in <i>A. dhakensis</i>, we conducted a transcriptomic analysis. The RNAseq results showed that the expression of a unique hemolysin <i>ahh1</i> and other virulence factors were regulated by UvrY. Complementation of Ahh1, one of the most important virulence factors, rescued the pore-formation phenotype of <i>uvrY</i> mutant in <i>C. elegans</i>; however, complementation of <i>ahh1</i> endogenous promoter-driven <i>ahh1</i> could not produce Ahh1 and rescue the virulence in the <i>uvrY</i> mutant. These findings suggest that UvrY is required for the expression of Ahh1 in <i>A. dhakensis</i>. Taken together, our results suggested that UvrY controls several different virulence factors and is required for the full virulence of <i>A. dhakensis</i>. The two-component regulator UvrY therefore a potential therapeutic target which is worthy of further study.
DOI: 10.6084/m9.figshare.12852045
title: Transcriptional remodeling during metacyclogenesis in <i>Trypanosoma cruzi</i> I

description: Metacyclogenesis is one of the most important processes in the life cycle of <i>Trypanosoma cruzi</i>. In this stage, noninfective epimastigotes become infective metacyclic trypomastigotes. However, the transcriptomic changes that occur during this transformation remain uncertain. Illumina RNA-sequencing of epimastigotes and metacyclic trypomastigotes belonging to <i>T. cruzi</i> DTU I was undertaken. Sequencing reads were aligned and mapped against the reference genome, differentially expressed genes between the two life cycle stages were identified, and metabolic pathways were reconstructed. Gene expression differed significantly between epimastigotes and metacyclic trypomastigotes. The cellular pathways that were mostly downregulated during metacyclogenesis involved glucose energy metabolism (glycolysis, pyruvate metabolism, the Krebs cycle, and oxidative phosphorylation), amino acid metabolism, and DNA replication. By contrast, the processes where an increase in gene expression was observed included those related to autophagy (particularly Atg7 and Atg8 transcripts), corroborating its importance during metacyclogenesis, endocytosis, by an increase in the expression of the AP-2 complex subunit alpha, protein processing in the endoplasmic reticulum and meiosis. Study findings indicate that in <i>T. cruzi</i> metacyclic trypomastigotes, metabolic processes are decreased, and expression of genes involved in specific cell cycle processes is increased to facilitate transformation to this infective stage.
DOI: 10.6084/m9.figshare.12344432.v2
title: UvrY is required for the full virulence of <i>Aeromonas dhakensis</i>

description: <i>Aeromonas dhakensis</i> is an emerging human pathogen which causes fast and severe infections worldwide. Under the gradual pressure of lacking useful antibiotics, finding a new strategy against <i>A. dhakensis</i> infection is urgent. To understand its pathogenesis, we created an <i>A. dhakensis</i> AAK1 mini-Tn10 transposon library to study the mechanism of <i>A. dhakensis</i> infection. By using a <i>Caenorhabditis elegans</i> model, we established a screening platform for the purpose of identifying attenuated mutants. The <i>uvrY</i> mutant, which conferred the most attenuated toxicity toward <i>C. elegans</i>, was identified. The <i>uvrY</i> mutant was also less virulent in C2C12 fibroblast and mice models, in line with <i>in vitro</i> results. To further elucidate the mechanism of UvrY in controlling the toxicity in <i>A. dhakensis</i>, we conducted a transcriptomic analysis. The RNAseq results showed that the expression of a unique hemolysin <i>ahh1</i> and other virulence factors were regulated by UvrY. Complementation of Ahh1, one of the most important virulence factors, rescued the pore-formation phenotype of <i>uvrY</i> mutant in <i>C. elegans</i>; however, complementation of <i>ahh1</i> endogenous promoter-driven <i>ahh1</i> could not produce Ahh1 and rescue the virulence in the <i>uvrY</i> mutant. These findings suggest that UvrY is required for the expression of Ahh1 in <i>A. dhakensis</i>. Taken together, our results suggested that UvrY controls several different virulence factors and is required for the full virulence of <i>A. dhakensis</i>. The two-component regulator UvrY therefore a potential therapeutic target which is worthy of further study.
DOI: 10.6084/m9.figshare.12852045.v2
title: Transcriptional remodeling during metacyclogenesis in <i>Trypanosoma cruzi</i> I

description: Metacyclogenesis is one of the most important processes in the life cycle of <i>Trypanosoma cruzi</i>. In this stage, noninfective epimastigotes become infective metacyclic trypomastigotes. However, the transcriptomic changes that occur during this transformation remain uncertain. Illumina RNA-sequencing of epimastigotes and metacyclic trypomastigotes belonging to <i>T. cruzi</i> DTU I was undertaken. Sequencing reads were aligned and mapped against the reference genome, differentially expressed genes between the two life cycle stages were identified, and metabolic pathways were reconstructed. Gene expression differed significantly between epimastigotes and metacyclic trypomastigotes. The cellular pathways that were mostly downregulated during metacyclogenesis involved glucose energy metabolism (glycolysis, pyruvate metabolism, the Krebs cycle, and oxidative phosphorylation), amino acid metabolism, and DNA replication. By contrast, the processes where an increase in gene expression was observed included those related to autophagy (particularly Atg7 and Atg8 transcripts), corroborating its importance during metacyclogenesis, endocytosis, by an increase in the expression of the AP-2 complex subunit alpha, protein processing in the endoplasmic reticulum and meiosis. Study findings indicate that in <i>T. cruzi</i> metacyclic trypomastigotes, metabolic processes are decreased, and expression of genes involved in specific cell cycle processes is increased to facilitate transformation to this infective stage.