cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.30446942
title: Pathogenicity and pathobiological characterization of a recombinant genotype I/II African swine fever virus in pigs

description: African swine fever virus (ASFV) is a highly contagious pathogen affecting domestic pigs and wild boar, causing substantial economic losses. Recently, a highly virulent recombinant ASFV strain combining genotypes I and II (rASFV I/II) emerged in Asia. Genotype II ASFV vaccine candidates have failed to effectively protect against rASFV I/II infection, presenting a critical challenge. Here, we investigated the pathobiological characteristics of rASFV I/II in domestic pigs. Ten healthy 7-week-old female pigs were intramuscularly inoculated with an rASFV I/II strain. Clinical signs, rectal temperatures, and samples were collected daily, and necropsies were conducted postmortem. All inoculated pigs succumbed to infection within 5–7 days post-inoculation (dpi), with a mean of 5.5 ± 0.7 dpi. High fever ( &gt; 40.5°C) was observed at an average onset of 2.6 ± 0.8 dpi, and the incubation period averaged 3.0 ± 1.1 dpi. Viral DNA was first detected in blood at 2 dpi, with viral genome copies increasing steadily. Postmortem analysis revealed severe congestive splenomegaly and hemorrhagic lymphadenopathy in all pigs. A preliminary comparison of histopathological lesions in early phase of viral infection showed that all three rASFV I/II-infected pigs showed endothelial injury lesions, while only one genotype II ASFV-infected pig showed this lesion. High viral DNA copy numbers were detected in all organs, particularly the liver, lymph nodes, spleen, lungs, and kidneys. These findings demonstrated distinct pathobiological features of rASFV I/II that warrant further investigation for their implications on disease control. The results also emphasized the urgent need for enhanced surveillance in Asia, rapid diagnostic methods, and effective vaccines targeting emerging ASFV variants.
DOI: 10.6084/m9.figshare.30446942.v1
title: Pathogenicity and pathobiological characterization of a recombinant genotype I/II African swine fever virus in pigs

description: African swine fever virus (ASFV) is a highly contagious pathogen affecting domestic pigs and wild boar, causing substantial economic losses. Recently, a highly virulent recombinant ASFV strain combining genotypes I and II (rASFV I/II) emerged in Asia. Genotype II ASFV vaccine candidates have failed to effectively protect against rASFV I/II infection, presenting a critical challenge. Here, we investigated the pathobiological characteristics of rASFV I/II in domestic pigs. Ten healthy 7-week-old female pigs were intramuscularly inoculated with an rASFV I/II strain. Clinical signs, rectal temperatures, and samples were collected daily, and necropsies were conducted postmortem. All inoculated pigs succumbed to infection within 5–7 days post-inoculation (dpi), with a mean of 5.5 ± 0.7 dpi. High fever ( &gt; 40.5°C) was observed at an average onset of 2.6 ± 0.8 dpi, and the incubation period averaged 3.0 ± 1.1 dpi. Viral DNA was first detected in blood at 2 dpi, with viral genome copies increasing steadily. Postmortem analysis revealed severe congestive splenomegaly and hemorrhagic lymphadenopathy in all pigs. A preliminary comparison of histopathological lesions in early phase of viral infection showed that all three rASFV I/II-infected pigs showed endothelial injury lesions, while only one genotype II ASFV-infected pig showed this lesion. High viral DNA copy numbers were detected in all organs, particularly the liver, lymph nodes, spleen, lungs, and kidneys. These findings demonstrated distinct pathobiological features of rASFV I/II that warrant further investigation for their implications on disease control. The results also emphasized the urgent need for enhanced surveillance in Asia, rapid diagnostic methods, and effective vaccines targeting emerging ASFV variants.
DOI: 10.6084/m9.figshare.29582033
title: Ferroptosis is important for <i>Toxoplasma gondii</i> replication and virulence <i>in vitro</i> and <i>in vivo</i>

description: The protozoan parasite <i>T. gondii</i> employs intricate mechanisms to exploit host cells while sustaining their viability, yet its interaction with ferroptosis – an iron-dependent cell death driven by lipid peroxidation – remains poorly defined. Here, we show <i>T. gondii</i> infection induces ferroptotic hallmarks in RAW264.7 macrophages, including elevated lactate dehydrogenase release, labile Fe<sup>2 +</sup> accumulation, reactive oxygen species (ROS) generation, and lipid peroxidation. Molecular analyses revealed infection-induced downregulation of ferroptosis suppressor GPX4 and upregulation of pro-ferroptotic ACSL4 in macrophages and mice. Mechanistically, the SLC7A11/GPX4 axis governed parasite growth: knockdown of these genes promoted <i>T. gondii</i> replication, whereas overexpression restricted proliferation. Pharmacological studies showed ferroptosis inhibitor Fer-1 suppressed intracellular parasite proliferation. Notably, GPX4 inhibitor RSL3 exhibited context-dependent effects: pre-infection treatment enhanced replication, while post-infection administration inhibited growth. Direct RSL3 exposure induced time-dependent growth arrest in extracellular tachyzoites, associated with disrupted transcriptomes, increased lipid ROS, and downregulated parasite antioxidant genes (<i>TgPRX2</i>, <i>TgTPX1/2</i>, <i>TgNXN</i>), indicating redox homoeostasis impairment. In vivo murine studies corroborated this biphasic effect: therapeutic RSL3 administration post-infection significantly reduced parasite burdens across multiple organs (spleen, liver, kidney, brain) and improved survival rates, while prophylactic pretreatment exacerbated disease progression. We propose RSL3 exerts direct parasiticidal effects via oxidative damage but also enables early nutrient acquisition from ferroptosis-compromised host cells. These findings establish ferroptosis as a critical node in <i>T. gondii</i> pathogenesis, highlighting the parasite’s hijacking of host iron-lipid metabolism. The dual role of ferroptosis regulators underscores the host-pathogen metabolic complexity and positions the SLC7A11/GPX4 axis as a promising therapeutic target.
DOI: 10.6084/m9.figshare.29582033.v1
title: Ferroptosis is important for <i>Toxoplasma gondii</i> replication and virulence <i>in vitro</i> and <i>in vivo</i>

description: The protozoan parasite <i>T. gondii</i> employs intricate mechanisms to exploit host cells while sustaining their viability, yet its interaction with ferroptosis – an iron-dependent cell death driven by lipid peroxidation – remains poorly defined. Here, we show <i>T. gondii</i> infection induces ferroptotic hallmarks in RAW264.7 macrophages, including elevated lactate dehydrogenase release, labile Fe<sup>2 +</sup> accumulation, reactive oxygen species (ROS) generation, and lipid peroxidation. Molecular analyses revealed infection-induced downregulation of ferroptosis suppressor GPX4 and upregulation of pro-ferroptotic ACSL4 in macrophages and mice. Mechanistically, the SLC7A11/GPX4 axis governed parasite growth: knockdown of these genes promoted <i>T. gondii</i> replication, whereas overexpression restricted proliferation. Pharmacological studies showed ferroptosis inhibitor Fer-1 suppressed intracellular parasite proliferation. Notably, GPX4 inhibitor RSL3 exhibited context-dependent effects: pre-infection treatment enhanced replication, while post-infection administration inhibited growth. Direct RSL3 exposure induced time-dependent growth arrest in extracellular tachyzoites, associated with disrupted transcriptomes, increased lipid ROS, and downregulated parasite antioxidant genes (<i>TgPRX2</i>, <i>TgTPX1/2</i>, <i>TgNXN</i>), indicating redox homoeostasis impairment. In vivo murine studies corroborated this biphasic effect: therapeutic RSL3 administration post-infection significantly reduced parasite burdens across multiple organs (spleen, liver, kidney, brain) and improved survival rates, while prophylactic pretreatment exacerbated disease progression. We propose RSL3 exerts direct parasiticidal effects via oxidative damage but also enables early nutrient acquisition from ferroptosis-compromised host cells. These findings establish ferroptosis as a critical node in <i>T. gondii</i> pathogenesis, highlighting the parasite’s hijacking of host iron-lipid metabolism. The dual role of ferroptosis regulators underscores the host-pathogen metabolic complexity and positions the SLC7A11/GPX4 axis as a promising therapeutic target.
DOI: 10.6084/m9.figshare.29039555
title: Stress responsive glycosylphosphatidylinositol-anchored protein SsGSP1 contributes to <i>Sclerotinia sclerotiorum</i> virulence

description: Fungal cell wall acts as a defense barrier, shielding the cell from varying environmental stresses. Cell wall proteins, such as glycosylphosphatidylinositol (GPI)-anchored proteins, are involved in swift and appropriate responses to minor environmental changes in fungi. However, the roles of these proteins in the pathogenic <i>Sclerotinia sclerotiorum</i> remain largely unexplored. Here, we identified a novel GPI-anchored protein in <i>S. sclerotiorum</i>, SsGSP1, comprising a Kre9_KNH domain. <i>SsGSP1</i> was upregulated during infection, and the loss-of-function mutants of <i>SsGSP1</i> exhibited the compromised cell wall integrity and reduced β-glucan content. During inoculation on <i>Arabidopsis thaliana</i>, <i>Nicotiana benthamiana</i>, and <i>Brassica napus</i>, the <i>SsGSP1</i>-deletion strains demonstrated the decreased virulence. The transgenic <i>A</i>. <i>thaliana</i> line carrying the sRNA targeting <i>SsGSP1</i> enhanced resistance to <i>S. sclerotiorum</i> via Host-Induced Gene Silencing (HIGS). The <i>SsGSP1</i>-deficient strains displayed the heightened sensitivity to various stresses, including osmotic pressure, oxidative stress, and heat shock. The yeast two-hybrid and BiFC assays confirmed that SsGSP1 interacted with the key stress-related proteins catalase SsCat2, heat shock protein Sshsp60, and ABC transporter SsBMR1. Accordingly, transcriptome analysis revealed that the disruption of <i>SsGSP1</i> downregulated the expression of genes involved in oxidative stress response, heat shock response, and chemical agent resistance. These results collectively delineate the intricate role of GPI-anchored protein SsGSP1 in β-glucan, cell wall integrity, and virulence and may act as a potential surface sensor to elicit signal transduction in response to environmental stresses in <i>S. sclerotiorum</i>.
DOI: 10.6084/m9.figshare.29039555.v4
title: Stress responsive glycosylphosphatidylinositol-anchored protein SsGSP1 contributes to <i>Sclerotinia sclerotiorum</i> virulence

description: Fungal cell wall acts as a defense barrier, shielding the cell from varying environmental stresses. Cell wall proteins, such as glycosylphosphatidylinositol (GPI)-anchored proteins, are involved in swift and appropriate responses to minor environmental changes in fungi. However, the roles of these proteins in the pathogenic <i>Sclerotinia sclerotiorum</i> remain largely unexplored. Here, we identified a novel GPI-anchored protein in <i>S. sclerotiorum</i>, SsGSP1, comprising a Kre9_KNH domain. <i>SsGSP1</i> was upregulated during infection, and the loss-of-function mutants of <i>SsGSP1</i> exhibited the compromised cell wall integrity and reduced β-glucan content. During inoculation on <i>Arabidopsis thaliana</i>, <i>Nicotiana benthamiana</i>, and <i>Brassica napus</i>, the <i>SsGSP1</i>-deletion strains demonstrated the decreased virulence. The transgenic <i>A</i>. <i>thaliana</i> line carrying the sRNA targeting <i>SsGSP1</i> enhanced resistance to <i>S. sclerotiorum</i> via Host-Induced Gene Silencing (HIGS). The <i>SsGSP1</i>-deficient strains displayed the heightened sensitivity to various stresses, including osmotic pressure, oxidative stress, and heat shock. The yeast two-hybrid and BiFC assays confirmed that SsGSP1 interacted with the key stress-related proteins catalase SsCat2, heat shock protein Sshsp60, and ABC transporter SsBMR1. Accordingly, transcriptome analysis revealed that the disruption of <i>SsGSP1</i> downregulated the expression of genes involved in oxidative stress response, heat shock response, and chemical agent resistance. These results collectively delineate the intricate role of GPI-anchored protein SsGSP1 in β-glucan, cell wall integrity, and virulence and may act as a potential surface sensor to elicit signal transduction in response to environmental stresses in <i>S. sclerotiorum</i>.
DOI: 10.6084/m9.figshare.30607395
title: ROS-induced allosteric modulation of NikR promotes <i>Helicobacter pylori</i> biofilm formation by attenuating FlgR-dependent inhibition of the molybdate transport system

description: <i>Helicobacter pylori</i> biofilm formation is crucial for its persistence and transmission, constituting a notable public health concern. Understanding the regulatory mechanisms driving biofilm initiation is vital for developing effective control strategies. This study reveals a previously uncharacterized regulatory mechanism where reactive oxygen species (ROS) promote <i>H. pylori</i> biofilm formation by modulating the key flagellar regulator FlgR and the molybdate transport system ModABD. We demonstrate that FlgR acts as a repressor of biofilm development. Mechanistically, FlgR inhibits the transcription of the <i>modABD</i> operon, essential for biofilm formation, by suppressing the activity of sigma factor σ<sup>28</sup>. Crucially, we identify the nickel-responsive regulator NikR as a repressor of <i>flgR</i> expression. ROS induces a conformational change in NikR, converting it to its DNA-binding holo-form, which directly binds the <i>flgR</i> promoter and represses its expression. This repression alleviates FlgR-mediated inhibition of σ<sup>28</sup>, thereby de-repressing the <i>modABD</i> operon and facilitating the transition from planktonic to biofilm growth. Our findings uncover a previously unknown ROS-NikR-FlgR-σ<sup>28</sup>-ModABD signaling axis governing <i>H. pylori</i> biofilm formation.
DOI: 10.6084/m9.figshare.30607395.v2
title: ROS-induced allosteric modulation of NikR promotes <i>Helicobacter pylori</i> biofilm formation by attenuating FlgR-dependent inhibition of the molybdate transport system

description: <i>Helicobacter pylori</i> biofilm formation is crucial for its persistence and transmission, constituting a notable public health concern. Understanding the regulatory mechanisms driving biofilm initiation is vital for developing effective control strategies. This study reveals a previously uncharacterized regulatory mechanism where reactive oxygen species (ROS) promote <i>H. pylori</i> biofilm formation by modulating the key flagellar regulator FlgR and the molybdate transport system ModABD. We demonstrate that FlgR acts as a repressor of biofilm development. Mechanistically, FlgR inhibits the transcription of the <i>modABD</i> operon, essential for biofilm formation, by suppressing the activity of sigma factor σ<sup>28</sup>. Crucially, we identify the nickel-responsive regulator NikR as a repressor of <i>flgR</i> expression. ROS induces a conformational change in NikR, converting it to its DNA-binding holo-form, which directly binds the <i>flgR</i> promoter and represses its expression. This repression alleviates FlgR-mediated inhibition of σ<sup>28</sup>, thereby de-repressing the <i>modABD</i> operon and facilitating the transition from planktonic to biofilm growth. Our findings uncover a previously unknown ROS-NikR-FlgR-σ<sup>28</sup>-ModABD signaling axis governing <i>H. pylori</i> biofilm formation.
DOI: 10.6084/m9.figshare.29039555.v3
title: Stress responsive glycosylphosphatidylinositol-anchored protein SsGSP1 contributes to <i>Sclerotinia sclerotiorum</i> virulence

description: Fungal cell wall acts as a defense barrier, shielding the cell from varying environmental stresses. Cell wall proteins, such as glycosylphosphatidylinositol (GPI)-anchored proteins, are involved in swift and appropriate responses to minor environmental changes in fungi. However, the roles of these proteins in the pathogenic <i>Sclerotinia sclerotiorum</i> remain largely unexplored. Here, we identified a novel GPI-anchored protein in <i>S. sclerotiorum</i>, SsGSP1, comprising a Kre9_KNH domain. <i>SsGSP1</i> was upregulated during infection, and the loss-of-function mutants of <i>SsGSP1</i> exhibited the compromised cell wall integrity and reduced β-glucan content. During inoculation on <i>Arabidopsis thaliana</i>, <i>Nicotiana benthamiana</i>, and <i>Brassica napus</i>, the <i>SsGSP1</i>-deletion strains demonstrated the decreased virulence. The transgenic <i>A</i>. <i>thaliana</i> line carrying the sRNA targeting <i>SsGSP1</i> enhanced resistance to <i>S. sclerotiorum</i> via Host-Induced Gene Silencing (HIGS). The <i>SsGSP1</i>-deficient strains displayed the heightened sensitivity to various stresses, including osmotic pressure, oxidative stress, and heat shock. The yeast two-hybrid and BiFC assays confirmed that SsGSP1 interacted with the key stress-related proteins catalase SsCat2, heat shock protein Sshsp60, and ABC transporter SsBMR1. Accordingly, transcriptome analysis revealed that the disruption of <i>SsGSP1</i> downregulated the expression of genes involved in oxidative stress response, heat shock response, and chemical agent resistance. These results collectively delineate the intricate role of GPI-anchored protein SsGSP1 in β-glucan, cell wall integrity, and virulence and may act as a potential surface sensor to elicit signal transduction in response to environmental stresses in <i>S. sclerotiorum</i>.
DOI: 10.6084/m9.figshare.29366261
title: Plasmids of two novel incompatibility groups IncFII<sub>pPROV114-NR</sub> and Inc<sub>pCHS4.1-3</sub> from <i>Providencia</i>

description: This study presents the genetic structure of two incompatibility (Inc) groups found in <i>Providencia</i>: the newly discovered IncFII<sub>pPROV114-NR</sub> and the newly designated Inc<sub>pCHS4.1–3</sub>. An extensive genomic comparison was performed on all 14 plasmids (three IncFII<sub>pPROV114-NR</sub> plasmids and 11 Inc<sub>pCHS4.1–3</sub> plasmids) from <i>Providencia</i>, including 12 newly sequenced in this study and two from GenBank. Three IncFII<sub>pPROV114-NR</sub> plasmids had similar conserved backbones but differed in accessory modules. The 11 Inc<sub>pCHS4.1–3</sub> plasmids fell into two groups according to differences in the conserved genes of the plasmid backbone. The accessory modules of 11 Inc<sub>pCHS4.1–3</sub> plasmids showed significant diversity, indicating numerous gene gains and losses, including in the Tn<i>1696-</i>related region, in Tn<i>7504</i>, in a 17.3-kb <i>sul2</i> region, and a 63.6-kb <i>bla</i><sub>NDM-1</sub> region. A minimum of 45 obtained antimicrobial resistance genes (ARGs) were identified in 13 of the 14 plasmids, covering resistance to 14 classes of antimicrobials and heavy metals. Five new mobile genetic elements (MGEs) were identified, including In2168, In1790, Tn<i>7500</i>, Tn<i>7501</i>, and Tn<i>7502</i>. Additionally, three MGEs, Tn<i>7499</i>, Tn<i>7503</i>, and Tn<i>7504</i> were newly designated. These two Inc group plasmids integrate abundant accessory modules that allow them to accumulate and distribute ARGs and improve the survivability of <i>Providencia</i> under the pressure of drug selection.
DOI: 10.6084/m9.figshare.29366261.v1
title: Plasmids of two novel incompatibility groups IncFII<sub>pPROV114-NR</sub> and Inc<sub>pCHS4.1-3</sub> from <i>Providencia</i>

description: This study presents the genetic structure of two incompatibility (Inc) groups found in <i>Providencia</i>: the newly discovered IncFII<sub>pPROV114-NR</sub> and the newly designated Inc<sub>pCHS4.1–3</sub>. An extensive genomic comparison was performed on all 14 plasmids (three IncFII<sub>pPROV114-NR</sub> plasmids and 11 Inc<sub>pCHS4.1–3</sub> plasmids) from <i>Providencia</i>, including 12 newly sequenced in this study and two from GenBank. Three IncFII<sub>pPROV114-NR</sub> plasmids had similar conserved backbones but differed in accessory modules. The 11 Inc<sub>pCHS4.1–3</sub> plasmids fell into two groups according to differences in the conserved genes of the plasmid backbone. The accessory modules of 11 Inc<sub>pCHS4.1–3</sub> plasmids showed significant diversity, indicating numerous gene gains and losses, including in the Tn<i>1696-</i>related region, in Tn<i>7504</i>, in a 17.3-kb <i>sul2</i> region, and a 63.6-kb <i>bla</i><sub>NDM-1</sub> region. A minimum of 45 obtained antimicrobial resistance genes (ARGs) were identified in 13 of the 14 plasmids, covering resistance to 14 classes of antimicrobials and heavy metals. Five new mobile genetic elements (MGEs) were identified, including In2168, In1790, Tn<i>7500</i>, Tn<i>7501</i>, and Tn<i>7502</i>. Additionally, three MGEs, Tn<i>7499</i>, Tn<i>7503</i>, and Tn<i>7504</i> were newly designated. These two Inc group plasmids integrate abundant accessory modules that allow them to accumulate and distribute ARGs and improve the survivability of <i>Providencia</i> under the pressure of drug selection.
DOI: 10.6084/m9.figshare.29846758
title: A novel <i>Klebsiella pneumoniae</i> diguanylate cyclase contributes to intestinal cell adhesion, biofilm formation, iron utilization, and <i>in vivo</i> virulence by gastrointestinal infection

description: <i>Klebsiella pneumoniae</i> is responsible for various infections such as bacteremia, urinary tract infections, pneumonia, and liver abscesses. Multidrug-resistant <i>K. pneumoniae</i> infections pose a critical public health threat, often associated with high mortality rates. The emergence of hypervirulent <i>K. pneumoniae</i> has also raised global health concerns due to its invasive disease potential. Clinical studies suggest intestinal colonization by <i>K. pneumoniae</i> as a risk factor for subsequent infections, but the underlying mechanisms remain unclear. Cyclic di-GMP (c-di-GMP), a bacterial signaling molecule synthesized by diguanylate cyclases (DGCs), controls various cellular processes and is absent in higher organisms, making it an attractive target for antimicrobial development. In this study, we identified a novel DGC, designated as DgcG, in <i>K. pneumoniae</i>, which plays a pivotal role in gastrointestinal colonization and pathogenesis. Using genetic deletion and complementation analyses in a bacteremia and liver abscesses-inducing strain Ca0437, we observed that DgcG promoted intestinal adherence, biofilm formation, iron utilization, and <i>in vivo</i> virulence. RT-qPCR showed that DgcG regulated genes involved in type 3 fimbrial expression and iron transport. In a gastrointestinal infection model of female BALB/cByl mice, <i>dgcG</i> deletion significantly reduced host mortality and bacterial load in the liver, spleen, and intestines, underscoring its role in enhancing bacterial survival and dissemination. Additionally, <i>dgcG</i> gene was found highly conserved and prevalent among diverse <i>K. pneumoniae</i> isolates. These findings provide new insights into c-di-GMP-mediated virulence regulation in <i>K. pneumoniae</i> and highlight DgcG as a potential therapeutic target for controlling <i>K. pneumoniae</i> infections, especially amidst the growing global antimicrobial resistance crisis.