cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.21155114
title: Effects of α and β-adrenergic signaling on innate immunity and Porphyromonas gingivalis virulence in an invertebrate model

description: To investigate the role of adrenergic signalling (AS) in the host immune response and <i>Porphyromonas gingivalis</i> virulence, we compared norepinephrine (NE) and isoproterenol (ISO) responses in <i>Galleria mellonella</i>. <i>P. gingivalis</i> infection was evaluated by survival; humoral immune responses (i.e. melanization and <i>cecropin</i> and <i>gloverin</i> mRNA expression); cellular immune responses (i.e. haemocyte count, nodulation by histology); and <i>P. gingivalis</i> recovery (CFU/mL). <i>P. gingivalis</i> was cultivated in the presence of ISO (PgISO) or NE and injected into the larvae for survival evaluation. Finally, we co-injected ISO and PgISO to evaluate the concomitant effects on the immune response and bacterial virulence. None of the ligands were toxic to the larvae; ISO increased haemocyte number, even after <i>P. gingivalis</i> infection, by mobilizing sessile haemocytes in a β-adrenergic-specific manner, while NE showed the opposite effect. ISO treatment reduced larval mortality and the number of recovered bacteria, while NE increased mortality and showed no effect on bacterial recovery. ISO and NE had similar effects on melanization and decreased the expression of cecropin. Although co-cultivation with NE and ISO increased the gene expression of bacterial virulence factors <i>in vitro</i>, only the injection of PgISO increased larval death, which was partially reversed by circulating ISO. Therefore, α- and β-adrenergic signalling had opposite effects after <i>P. gingivalis</i> infection. Ultimately, the catecholamine influence on the immune response overcame the effect of more virulent strains. The effect of AS directly on the pathogen found <i>in vitro</i> did not translate to the <i>in vivo</i> setting.
DOI: 10.6084/m9.figshare.21155114.v1
title: Effects of α and β-adrenergic signaling on innate immunity and Porphyromonas gingivalis virulence in an invertebrate model

description: To investigate the role of adrenergic signalling (AS) in the host immune response and <i>Porphyromonas gingivalis</i> virulence, we compared norepinephrine (NE) and isoproterenol (ISO) responses in <i>Galleria mellonella</i>. <i>P. gingivalis</i> infection was evaluated by survival; humoral immune responses (i.e. melanization and <i>cecropin</i> and <i>gloverin</i> mRNA expression); cellular immune responses (i.e. haemocyte count, nodulation by histology); and <i>P. gingivalis</i> recovery (CFU/mL). <i>P. gingivalis</i> was cultivated in the presence of ISO (PgISO) or NE and injected into the larvae for survival evaluation. Finally, we co-injected ISO and PgISO to evaluate the concomitant effects on the immune response and bacterial virulence. None of the ligands were toxic to the larvae; ISO increased haemocyte number, even after <i>P. gingivalis</i> infection, by mobilizing sessile haemocytes in a β-adrenergic-specific manner, while NE showed the opposite effect. ISO treatment reduced larval mortality and the number of recovered bacteria, while NE increased mortality and showed no effect on bacterial recovery. ISO and NE had similar effects on melanization and decreased the expression of cecropin. Although co-cultivation with NE and ISO increased the gene expression of bacterial virulence factors <i>in vitro</i>, only the injection of PgISO increased larval death, which was partially reversed by circulating ISO. Therefore, α- and β-adrenergic signalling had opposite effects after <i>P. gingivalis</i> infection. Ultimately, the catecholamine influence on the immune response overcame the effect of more virulent strains. The effect of AS directly on the pathogen found <i>in vitro</i> did not translate to the <i>in vivo</i> setting.
DOI: 10.6084/m9.figshare.21581040
title: Molecular characterization of extraintestinal and diarrheagenic <i>Escherichia coli</i> blood isolates

description: Pathogenic <i>E. coli</i> strains can be classified into two major groups, based on the presence of specific virulence factors: extraintestinal pathogenic <i>E. coli</i> (ExPEC) and diarrheagenic <i>E. coli</i> (DEC). Several case reports describe that DEC can cause bloodstream infections in some rare cases. This mainly concerns a few specific sequence types that express virulence factors from both ExPEC and DEC. In this study, we retrospectively analysed 234 <i>E. coli</i> blood isolates with whole genome sequencing (WGS). WGS was performed on an Illumina NovaSeq6000. Genotyping was performed using BioNumerics software. The presence of genes was determined with a minimum percentage sequence identity (ID) threshold of 95% and a minimum length for sequence coverage of 95%. Three of the 234 (1.28%) isolates were defined as DEC, 182 (77.78%) as ExPEC, and 49 (20.94%) did not carry pathotype-associated virulence genes. We identified 112 different virulence genes, 48 O-antigens, and 28 H-antigens 82 STs, among the 234 analyzed isolates. ST131 and ST88 were related to healthcare-associated infections. This study provides insight into the prevalence of virulence factors in a large set of <i>E. coli</i> blood isolates from the UZ Brussel. It illustrates high diversity in virulence profiles and highlights the potential of DEC to carry virulence factors associated with extraintestinal infections, making it possible for unusual pathotypes to invade and survive in the bloodstream causing bacteraemia. Diarrheagenic strains causing bacteremia are rare and presently underreported, but modern sequencing techniques will better underscore their importance.
DOI: 10.6084/m9.figshare.21581040.v2
title: Molecular characterization of extraintestinal and diarrheagenic <i>Escherichia coli</i> blood isolates

description: Pathogenic <i>E. coli</i> strains can be classified into two major groups, based on the presence of specific virulence factors: extraintestinal pathogenic <i>E. coli</i> (ExPEC) and diarrheagenic <i>E. coli</i> (DEC). Several case reports describe that DEC can cause bloodstream infections in some rare cases. This mainly concerns a few specific sequence types that express virulence factors from both ExPEC and DEC. In this study, we retrospectively analysed 234 <i>E. coli</i> blood isolates with whole genome sequencing (WGS). WGS was performed on an Illumina NovaSeq6000. Genotyping was performed using BioNumerics software. The presence of genes was determined with a minimum percentage sequence identity (ID) threshold of 95% and a minimum length for sequence coverage of 95%. Three of the 234 (1.28%) isolates were defined as DEC, 182 (77.78%) as ExPEC, and 49 (20.94%) did not carry pathotype-associated virulence genes. We identified 112 different virulence genes, 48 O-antigens, and 28 H-antigens 82 STs, among the 234 analyzed isolates. ST131 and ST88 were related to healthcare-associated infections. This study provides insight into the prevalence of virulence factors in a large set of <i>E. coli</i> blood isolates from the UZ Brussel. It illustrates high diversity in virulence profiles and highlights the potential of DEC to carry virulence factors associated with extraintestinal infections, making it possible for unusual pathotypes to invade and survive in the bloodstream causing bacteraemia. Diarrheagenic strains causing bacteremia are rare and presently underreported, but modern sequencing techniques will better underscore their importance.
DOI: 10.6084/m9.figshare.19572992
title: PHB2 affects the virulence of Vip3Aa to Sf9 cells through internalization and mitochondrial stability

description: The vegetative insecticidal proteins (Vip3A) secreted by some <i>Bacillus thuringiensis</i> (Bt) strains during vegetative growth are regarded as a new generation of insecticidal toxins. Like insecticidal crystal proteins, they are also used in transgenic crops to control pests. However, their insecticidal mechanisms are far less defined than those of insecticidal crystal protein. Prohibitin 2 (PHB2) is a potential Vip3Aa binding receptor identified from the membrane of Sf9 cells in our previous work. In this paper, we demonstrated the interaction between Vip3Aa and PHB2 using pull-down, dot blotting, microscale thermophoresis, and co-immunoprecipitation assays. PHB2 is distributed on the cell membrane and in the cytoplasm, and the co-localization of PHB2 and Vip3Aa was observed in Sf9 cells using a confocal laser scanning microscope. Moreover, PHB2 could interact with scavenger receptor-C via its SPFH (stomatin, prohibitin, flotillin, and HflK/C) domain. Downregulation of <i>phb2</i> expression reduced the degree of internalization of Vip3Aa, exacerbated Vip3Aa-mediated mitochondrial damage, and increased Vip3Aa toxicity to Sf9 cells. This suggested that PHB2 performs two different functions: Acting as an interacting partner to facilitate the internalization of Vip3Aa into Sf9 cells and maintaining the stability of mitochondria. The latter has a more important influence on the virulence of Vip3Aa.
DOI: 10.6084/m9.figshare.19572992.v1
title: PHB2 affects the virulence of Vip3Aa to Sf9 cells through internalization and mitochondrial stability

description: The vegetative insecticidal proteins (Vip3A) secreted by some <i>Bacillus thuringiensis</i> (Bt) strains during vegetative growth are regarded as a new generation of insecticidal toxins. Like insecticidal crystal proteins, they are also used in transgenic crops to control pests. However, their insecticidal mechanisms are far less defined than those of insecticidal crystal protein. Prohibitin 2 (PHB2) is a potential Vip3Aa binding receptor identified from the membrane of Sf9 cells in our previous work. In this paper, we demonstrated the interaction between Vip3Aa and PHB2 using pull-down, dot blotting, microscale thermophoresis, and co-immunoprecipitation assays. PHB2 is distributed on the cell membrane and in the cytoplasm, and the co-localization of PHB2 and Vip3Aa was observed in Sf9 cells using a confocal laser scanning microscope. Moreover, PHB2 could interact with scavenger receptor-C via its SPFH (stomatin, prohibitin, flotillin, and HflK/C) domain. Downregulation of <i>phb2</i> expression reduced the degree of internalization of Vip3Aa, exacerbated Vip3Aa-mediated mitochondrial damage, and increased Vip3Aa toxicity to Sf9 cells. This suggested that PHB2 performs two different functions: Acting as an interacting partner to facilitate the internalization of Vip3Aa into Sf9 cells and maintaining the stability of mitochondria. The latter has a more important influence on the virulence of Vip3Aa.
DOI: 10.6084/m9.figshare.21581040.v1
title: Molecular characterization of extraintestinal and diarrheagenic <i>Escherichia coli</i> blood isolates

description: Pathogenic <i>E. coli</i> strains can be classified into two major groups, based on the presence of specific virulence factors: extraintestinal pathogenic <i>E. coli</i> (ExPEC) and diarrheagenic <i>E. coli</i> (DEC). Several case reports describe that DEC can cause bloodstream infections in some rare cases. This mainly concerns a few specific sequence types that express virulence factors from both ExPEC and DEC. In this study, we retrospectively analysed 234 <i>E. coli</i> blood isolates with whole genome sequencing (WGS). WGS was performed on an Illumina NovaSeq6000. Genotyping was performed using BioNumerics software. The presence of genes was determined with a minimum percentage sequence identity (ID) threshold of 95% and a minimum length for sequence coverage of 95%. Three of the 234 (1.28%) isolates were defined as DEC, 182 (77.78%) as ExPEC, and 49 (20.94%) did not carry pathotype-associated virulence genes. We identified 112 different virulence genes, 48 O-antigens, and 28 H-antigens 82 STs, among the 234 analyzed isolates. ST131 and ST88 were related to healthcare-associated infections. This study provides insight into the prevalence of virulence factors in a large set of <i>E. coli</i> blood isolates from the UZ Brussel. It illustrates high diversity in virulence profiles and highlights the potential of DEC to carry virulence factors associated with extraintestinal infections, making it possible for unusual pathotypes to invade and survive in the bloodstream causing bacteraemia. Diarrheagenic strains causing bacteremia are rare and presently underreported, but modern sequencing techniques will better underscore their importance.
DOI: 10.6084/m9.figshare.19611977
title: Pathogenesis of recent Lassa virus isolates from lineages II and VII in cynomolgus monkeys

description: The area of Lassa virus (LASV) circulation is expanding, with the emergence of highly pathogenic new LASV lineages. Benin recently became an endemic country for LASV and has seen the emergence of a new LASV lineage (VII). The first two outbreaks in 2014 and 2016 showed a relatively high mortality rate compared to other outbreaks. We infected cynomolgus monkeys with two strains belonging to lineage II and lineage VII that were isolated from deceased patients during the 2016 outbreak in Benin. The lineage VII strain (L7) caused uniform mortality. Death was associated with uncontrolled viral replication, unbalanced inflammatory responses characterized by increased concentrations of pro- and anti-inflammatory mediators, and the absence of efficient immune responses, resembling the pathogenesis associated with the prototypic Josiah strain in monkeys. The lineage II strain (L2) showed apparently lower virulence than its counterpart, with a prolonged time to death and a lower mortality rate. Prolonged survival was associated with better control of viral replication, a moderate inflammatory response, and efficient <i>T</i>-cell responses. Transcriptomic analyses also highlighted important differences in the immune responses associated with the outcome. Both strains caused strong inflammation in several organs. Notably, meningitis and encephalitis were observed in the cerebral cortex and cerebellum in all monkeys, independently of the outcome. Due to their apparently high pathogenicity, emerging strains from lineage VII should be considered in preclinical vaccine testing. Lineage II would also be beneficial in pathogenesis studies to study the entire spectrum of Lassa fever severity.
DOI: 10.6084/m9.figshare.19611977.v1
title: Pathogenesis of recent Lassa virus isolates from lineages II and VII in cynomolgus monkeys

description: The area of Lassa virus (LASV) circulation is expanding, with the emergence of highly pathogenic new LASV lineages. Benin recently became an endemic country for LASV and has seen the emergence of a new LASV lineage (VII). The first two outbreaks in 2014 and 2016 showed a relatively high mortality rate compared to other outbreaks. We infected cynomolgus monkeys with two strains belonging to lineage II and lineage VII that were isolated from deceased patients during the 2016 outbreak in Benin. The lineage VII strain (L7) caused uniform mortality. Death was associated with uncontrolled viral replication, unbalanced inflammatory responses characterized by increased concentrations of pro- and anti-inflammatory mediators, and the absence of efficient immune responses, resembling the pathogenesis associated with the prototypic Josiah strain in monkeys. The lineage II strain (L2) showed apparently lower virulence than its counterpart, with a prolonged time to death and a lower mortality rate. Prolonged survival was associated with better control of viral replication, a moderate inflammatory response, and efficient <i>T</i>-cell responses. Transcriptomic analyses also highlighted important differences in the immune responses associated with the outcome. Both strains caused strong inflammation in several organs. Notably, meningitis and encephalitis were observed in the cerebral cortex and cerebellum in all monkeys, independently of the outcome. Due to their apparently high pathogenicity, emerging strains from lineage VII should be considered in preclinical vaccine testing. Lineage II would also be beneficial in pathogenesis studies to study the entire spectrum of Lassa fever severity.
DOI: 10.6084/m9.figshare.19531154
title: Pathogenicity and virulence of Marburg virus

description: Marburg virus (MARV) has been a major concern since 1967, with two major outbreaks occurring in 1998 and 2004. Infection from MARV results in severe hemorrhagic fever, causing organ dysfunction and death. Exposure to fruit bats in caves and mines, and human-to-human transmission had major roles in the amplification of MARV outbreaks in African countries. The high fatality rate of up to 90% demands the broad study of MARV diseases (MVD) that correspond with MARV infection. Since large outbreaks are rare for MARV, clinical investigations are often inadequate for providing the substantial data necessary to determine the treatment of MARV disease. Therefore, an overall review may contribute to minimizing the limitations associated with future medical research and improve the clinical management of MVD. In this review, we sought to analyze and amalgamate significant information regarding MARV disease epidemics, pathophysiology, and management approaches to provide a better understanding of this deadly virus and the associated infection.
DOI: 10.6084/m9.figshare.17916578
title: A temperate <i>Siphoviridae</i> bacteriophage isolate from Siberian tiger enhances the virulence of methicillin-resistant <i>Staphylococcus aureus</i> through distinct mechanisms

description: The emergence and worldwide spread of Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) pose a threat to human health. While bacteriophages are recognized as an effective alternative to treat infections caused by drug resistant pathogens, some bacteriophages in particular the temperate bacteriophage may also influence the virulence of the host bacteria in distinct ways. In this study, we isolated a bacteriophage vB_Saus_PHB21 from an epidermal sample of Siberian tiger (<i>Panthera tigris altaica</i>) using an MRSA strain SA14 as the indicator. Our following laboratory tests and whole genome sequencing analyses revealed that vB_Saus_PHB21 was a temperate bacteriophage belonging to the <i>Siphoviridae</i> family, and this bacteriophage did not contain any virulence genes. However, the integration of PHB21 genome into the host MRSA increased the bacterial capacities of cell adhesion, anti-phagocytosis, and biofilm formation. Challenge of the lysogenic strain (SA14<sup>+</sup>) caused severe mortalities in both <i>Galleria mellonella</i> and mouse models. Mice challenged with SA14<sup>+</sup> showed more serious organ lesions and produced higher inflammatory cytokines (IL-8, IFN-γ and TNF-α) compared to those challenged with SA14. In mechanism, we found the integration of PHB21 genome caused the upregulated expression of many genes encoding products involved in bacterial biofilm formation, adherence to host cells, anti-phagocytosis, and virulence. This study may provide novel knowledge of “bacteria-phage-interactions” in MRSA.
DOI: 10.6084/m9.figshare.17916578.v1
title: A temperate <i>Siphoviridae</i> bacteriophage isolate from Siberian tiger enhances the virulence of methicillin-resistant <i>Staphylococcus aureus</i> through distinct mechanisms

description: The emergence and worldwide spread of Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) pose a threat to human health. While bacteriophages are recognized as an effective alternative to treat infections caused by drug resistant pathogens, some bacteriophages in particular the temperate bacteriophage may also influence the virulence of the host bacteria in distinct ways. In this study, we isolated a bacteriophage vB_Saus_PHB21 from an epidermal sample of Siberian tiger (<i>Panthera tigris altaica</i>) using an MRSA strain SA14 as the indicator. Our following laboratory tests and whole genome sequencing analyses revealed that vB_Saus_PHB21 was a temperate bacteriophage belonging to the <i>Siphoviridae</i> family, and this bacteriophage did not contain any virulence genes. However, the integration of PHB21 genome into the host MRSA increased the bacterial capacities of cell adhesion, anti-phagocytosis, and biofilm formation. Challenge of the lysogenic strain (SA14<sup>+</sup>) caused severe mortalities in both <i>Galleria mellonella</i> and mouse models. Mice challenged with SA14<sup>+</sup> showed more serious organ lesions and produced higher inflammatory cytokines (IL-8, IFN-γ and TNF-α) compared to those challenged with SA14. In mechanism, we found the integration of PHB21 genome caused the upregulated expression of many genes encoding products involved in bacterial biofilm formation, adherence to host cells, anti-phagocytosis, and virulence. This study may provide novel knowledge of “bacteria-phage-interactions” in MRSA.
DOI: 10.6084/m9.figshare.19153871
title: From environmental adaptation to host survival: Attributes that mediate pathogenicity of <i>Candida auris</i>

description: <i>Candida</i> species are a major cause of invasive fungal infections. While <i>Candida albicans, C. glabrata, C. parapsilosis</i>, and <i>C. tropicalis</i> are the most dominant species causing life-threatening candidiasis, <i>C. auris</i> recently emerged as a new species causing invasive infections with high rates of clinical treatment failures. To mimic initial phases of systemic <i>Candida</i> infections with dissemination <i>via</i> the bloodstream and to elucidate the pathogenic potential of <i>C. auris</i>, we used an <i>ex vivo</i> whole blood infection model. Similar to other clinically relevant <i>Candida</i> spp., <i>C. auris</i> is efficiently killed in human blood, but showed characteristic patterns of immune cell association, survival rates, and cytokine induction. Dual-species transcriptional profiling of <i>C. auris</i>-infected blood revealed a unique <i>C. auris</i> gene expression program during infection, while the host response proofed similar and conserved compared to other <i>Candida</i> species. <i>C. auris</i>-specific responses included adaptation and survival strategies, such as counteracting oxidative burst of immune cells, but also expression of potential virulence factors, (drug) transporters, and cell surface-associated genes. Despite comparable pathogenicity to other <i>Candida</i> species in our model, <i>C. auris</i>-specific transcriptional adaptations as well as its increased stress resistance and long-term environmental survival, likely contribute to the high risk of contamination and distribution in a nosocomial setting. Moreover, infections of neutrophils with pre-starved <i>C. auris</i> cells suggest that environmental preconditioning can have modulatory effects on the early host interaction. In summary, we present novel insights into <i>C. auris</i> pathogenicity, revealing adaptations to human blood and environmental niches distinctive from other <i>Candida</i> species.