cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.29126897.v1
title: Genetic evolution and alterations in pathogenicity of highly pathogenic porcine reproductive and respiratory syndrome virus

description: Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) and HP-PRRSV variant strains remain prevalent in China and Southeast Asian countries. However, their epidemiological aspects, genomic characteristics, relationships with vaccine strains, and changes in pathogenicity remain unclear. In this study, 2509 global L8.7 ORF5 sequences were utilized for analysis, we classified L8.7 into 7 groups (L8.7.1-L8.7.7). L8.7.1-L8.7.3 strains corresponded to previously reported classical PRRSVs, intermediate strains, and HP-PRRSVs, respectively, whereas L8.7.4-L8.7.7 were designated HP-like PRRSVs. Statistical analysis revealed that HP-like PRRSVs were the most prevalent among L8.7 strains, and L8.7.5 and L8.7.6 strains accounted for the highest proportions in recent years. A comprehensive analysis of the genome revealed that the majority (72.15%) of L8.7 strains presented a wild-type phenotype. Evolution rate analysis revealed that the evolution rate of L8.7.3-L8.7.7 PRRSV in China was reduced by about 4.1 times after the use of HP-PRRSV MLV. Pathogenicity test results indicate that in comparison with HP-PRRSV (L8.7.3: HuN4), the HP-like PRRSV strains (L8.7.5: DLF; L8.7.6: DLW) presented reduced pathogenicity in piglets while maintaining relatively high virulence. In summary, this study systematically elucidated the epidemiological dynamics, evolutionary trends, relationships with vaccine strains, and changes in pathogenicity associated with L8.7 strains, providing crucial data to support prevention and control strategies against L8.7 PRRSV.
DOI: 10.6084/m9.figshare.30621826
title: Carbon source-driven downregulation of the sRNA AmiL enhances <i>Pseudomonas aeruginosa</i> virulence during acute lung infection

description: <i>Pseudomonas aeruginosa</i> is a major opportunistic pathogen that causes severe acute lung infection. The ability of <i>P. aeruginosa</i> to precisely self-regulate its virulence factors is crucial for enhancing pathogenicity and establishing infection. However, how the bacterium dynamically adjusts virulence gene expression in response to host interaction remains to be elucidated. Here, transcriptome profiling revealed that infection of A549 alveolar epithelial cells significantly upregulated virulence genes associated with the type III secretion system (T3SS) and quorum sensing (QS) in <i>P. aeruginosa</i> PAO1, compared to a standard laboratory growth condition. In contrast, genes of the <i>amiEBCRS</i> operon were markedly downregulated during infection. Notably, AmiL, the leader small RNA (sRNA) of the operon, exhibited consistently reduced expression across multiple <i>P. aeruginosa</i> infection models, including A549 cells, mouse lungs, and clinical isolates. AmiL expression was primarily repressed by succinate-mediated carbon catabolite repression (CCR) during the early stage of infection, and later by the transcription factor ArgR as succinate levels declined. Functional analyses showed AmiL bound to the mRNAs of the T3SS effector gene <i>exoT</i> and the hydrogen cyanide synthesis gene <i>hcnC</i>, repressing their expression and thereby attenuating PAO1 virulence. Furthermore, deletion of <i>amiL</i> gene enhanced the cytotoxicity of PAO1 in A549 cells, <i>Galleria mellonella</i> larvae, and a mouse lung infection model, resulting in more severe tissue damage and increased mortality. Therefore, our findings demonstrate that <i>P. aeruginosa</i> strategically downregulates AmiL in response to carbon source changes to enhance its virulence and pathogenicity during acute lung infection, and highlight a potential target for antibacterial therapy.
DOI: 10.6084/m9.figshare.30621826.v2
title: Carbon source-driven downregulation of the sRNA AmiL enhances <i>Pseudomonas aeruginosa</i> virulence during acute lung infection

description: <i>Pseudomonas aeruginosa</i> is a major opportunistic pathogen that causes severe acute lung infection. The ability of <i>P. aeruginosa</i> to precisely self-regulate its virulence factors is crucial for enhancing pathogenicity and establishing infection. However, how the bacterium dynamically adjusts virulence gene expression in response to host interaction remains to be elucidated. Here, transcriptome profiling revealed that infection of A549 alveolar epithelial cells significantly upregulated virulence genes associated with the type III secretion system (T3SS) and quorum sensing (QS) in <i>P. aeruginosa</i> PAO1, compared to a standard laboratory growth condition. In contrast, genes of the <i>amiEBCRS</i> operon were markedly downregulated during infection. Notably, AmiL, the leader small RNA (sRNA) of the operon, exhibited consistently reduced expression across multiple <i>P. aeruginosa</i> infection models, including A549 cells, mouse lungs, and clinical isolates. AmiL expression was primarily repressed by succinate-mediated carbon catabolite repression (CCR) during the early stage of infection, and later by the transcription factor ArgR as succinate levels declined. Functional analyses showed AmiL bound to the mRNAs of the T3SS effector gene <i>exoT</i> and the hydrogen cyanide synthesis gene <i>hcnC</i>, repressing their expression and thereby attenuating PAO1 virulence. Furthermore, deletion of <i>amiL</i> gene enhanced the cytotoxicity of PAO1 in A549 cells, <i>Galleria mellonella</i> larvae, and a mouse lung infection model, resulting in more severe tissue damage and increased mortality. Therefore, our findings demonstrate that <i>P. aeruginosa</i> strategically downregulates AmiL in response to carbon source changes to enhance its virulence and pathogenicity during acute lung infection, and highlight a potential target for antibacterial therapy.
DOI: 10.6084/m9.figshare.28381424
title: Dual roles of exostosin glycosyltransferase 1 in Zika virus infection

description: Many factors involved in heparan sulfate (HS) biosynthesis and metabolism have been reported to play roles in viral infection. However, the detailed mechanisms are still not fully understood. In this study, we report that exostosin glycosyltransferase 1 (EXT1), the HS polymerase, is a critical regulatory factor for Zika virus (ZIKV) infection. Knocking out EXT1 dramatically restricts ZIKV infection, which is not due to the inhibition of virus entry resulting from HS deficiency, but mediated by the downregulation of autophagy. Induction of autophagy promotes ZIKV infection, and attenuated autophagy is found in distinct EXT1 knockout (EXT1-KO) cell lines. Induction of autophagy by rapamycin can relieve the ZIKV production defect in EXT1-KO cells. While over-expressing EXT1 results in the reduction of ZIKV production by targeting the viral envelope (E) protein and non-structural protein NS3 in a proteasome-dependent degradation manner. The different roles of EXT1 in ZIKV infection are further confirmed by the data that knocking down EXT1 at the early stage of ZIKV infection represses viral infection, whereas the increase of ZIKV infection is observed when knocking down EXT1 at the late stage of viral infection. This study discovers previously unrecognized intricate roles of EXT1 in ZIKV infection.
DOI: 10.6084/m9.figshare.28381424.v1
title: Dual roles of exostosin glycosyltransferase 1 in Zika virus infection

description: Many factors involved in heparan sulfate (HS) biosynthesis and metabolism have been reported to play roles in viral infection. However, the detailed mechanisms are still not fully understood. In this study, we report that exostosin glycosyltransferase 1 (EXT1), the HS polymerase, is a critical regulatory factor for Zika virus (ZIKV) infection. Knocking out EXT1 dramatically restricts ZIKV infection, which is not due to the inhibition of virus entry resulting from HS deficiency, but mediated by the downregulation of autophagy. Induction of autophagy promotes ZIKV infection, and attenuated autophagy is found in distinct EXT1 knockout (EXT1-KO) cell lines. Induction of autophagy by rapamycin can relieve the ZIKV production defect in EXT1-KO cells. While over-expressing EXT1 results in the reduction of ZIKV production by targeting the viral envelope (E) protein and non-structural protein NS3 in a proteasome-dependent degradation manner. The different roles of EXT1 in ZIKV infection are further confirmed by the data that knocking down EXT1 at the early stage of ZIKV infection represses viral infection, whereas the increase of ZIKV infection is observed when knocking down EXT1 at the late stage of viral infection. This study discovers previously unrecognized intricate roles of EXT1 in ZIKV infection.
DOI: 10.6084/m9.figshare.29968201
title: Novel insights into the genetic basis and transcriptomic elucidation of virulence attenuation in <i>Pseudomonas syringae</i> pv. <i>actinidiae</i> variants

description: <i>Pseudomonas syringae</i> pv. <i>actinidiae</i> (Psa) is the causal agent of kiwifruit bacterial canker, but the factors affecting its pathogenicity in natural settings remain poorly explored. In this study, we isolated two Psa strains, G126 and G282, from infected kiwifruit orchards in Guizhou Province of China. Both isolates, categorized as Psa-biovar 3, were confirmed through Psa3-specific primers and phylogenomic analysis. Pathogenicity assays on kiwifruit cultivar “Hongyang” leaves and branches showed significantly reduced numbers of necrotic spots and reduced lesion sizes upon infection with G282 compared to the G1 positive control strain, while G126 showed a nonpathogenic phenotype. Additionally, both strains failed to induce a hypersensitive response in nonhost <i>Nicotiana tabacum</i> plants and exhibited significantly reduced promoter activity of the <i>hrpR/S</i>, <i>hrpL</i>, and <i>hrpA</i> genes, which are crucial for the type III secretion system (T3SS). Genomic sequencing revealed that the T3SS of G126 was defective due to a single-nucleotide polymorphism in the <i>hrpR</i> gene, while G282 was entirely deficient in the type VI secretion system (T6SS), which potentially regulates the expression of T3SS genes. Transcriptomic analysis showed widespread alterations in key aspects of the secretion system, protein transport, and signal transduction, further supporting the phenotype characteristics exhibited by the strains. This study enhances our understanding of the genetic basis of nonpathogenic and partially pathogenic Psa isolates, highlighting the functional interdependencies between T3SS and T6SS.
DOI: 10.6084/m9.figshare.29968201.v1
title: Novel insights into the genetic basis and transcriptomic elucidation of virulence attenuation in <i>Pseudomonas syringae</i> pv. <i>actinidiae</i> variants

description: <i>Pseudomonas syringae</i> pv. <i>actinidiae</i> (Psa) is the causal agent of kiwifruit bacterial canker, but the factors affecting its pathogenicity in natural settings remain poorly explored. In this study, we isolated two Psa strains, G126 and G282, from infected kiwifruit orchards in Guizhou Province of China. Both isolates, categorized as Psa-biovar 3, were confirmed through Psa3-specific primers and phylogenomic analysis. Pathogenicity assays on kiwifruit cultivar “Hongyang” leaves and branches showed significantly reduced numbers of necrotic spots and reduced lesion sizes upon infection with G282 compared to the G1 positive control strain, while G126 showed a nonpathogenic phenotype. Additionally, both strains failed to induce a hypersensitive response in nonhost <i>Nicotiana tabacum</i> plants and exhibited significantly reduced promoter activity of the <i>hrpR/S</i>, <i>hrpL</i>, and <i>hrpA</i> genes, which are crucial for the type III secretion system (T3SS). Genomic sequencing revealed that the T3SS of G126 was defective due to a single-nucleotide polymorphism in the <i>hrpR</i> gene, while G282 was entirely deficient in the type VI secretion system (T6SS), which potentially regulates the expression of T3SS genes. Transcriptomic analysis showed widespread alterations in key aspects of the secretion system, protein transport, and signal transduction, further supporting the phenotype characteristics exhibited by the strains. This study enhances our understanding of the genetic basis of nonpathogenic and partially pathogenic Psa isolates, highlighting the functional interdependencies between T3SS and T6SS.
DOI: 10.6084/m9.figshare.30621826.v1
title: Carbon source-driven downregulation of the sRNA AmiL enhances <i>pseudomonas aeruginosa</i> virulence during acute lung infection

description: <i>Pseudomonas aeruginosa</i> is a major opportunistic pathogen that causes severe acute lung infection. The ability of <i>P. aeruginosa</i> to precisely self-regulate its virulence factors is crucial for enhancing pathogenicity and establishing infection. However, how the bacterium dynamically adjusts virulence gene expression in response to host interaction remains to be elucidated. Here, transcriptome profiling revealed that infection of A549 alveolar epithelial cells significantly upregulated virulence genes associated with the type III secretion system (T3SS) and quorum sensing (QS) in <i>P. aeruginosa</i> PAO1, compared to a standard laboratory growth condition. In contrast, genes of the <i>amiEBCRS</i> operon were markedly downregulated during infection. Notably, AmiL, the leader small RNA (sRNA) of the operon, exhibited consistently reduced expression across multiple <i>P. aeruginosa</i> infection models, including A549 cells, mouse lungs, and clinical isolates. AmiL expression was primarily repressed by succinate-mediated carbon catabolite repression (CCR) during the early stage of infection, and later by the transcription factor ArgR as succinate levels declined. Functional analyses showed AmiL bound to the mRNAs of the T3SS effector gene <i>exoT</i> and the hydrogen cyanide synthesis gene <i>hcnC</i>, repressing their expression and thereby attenuating PAO1 virulence. Furthermore, deletion of <i>amiL</i> gene enhanced the cytotoxicity of PAO1 in A549 cells, <i>Galleria mellonella</i> larvae, and a mouse lung infection model, resulting in more severe tissue damage and increased mortality. Therefore, our findings demonstrate that <i>P. aeruginosa</i> strategically downregulates AmiL in response to carbon source changes to enhance its virulence and pathogenicity during acute lung infection, and highlight a potential target for antibacterial therapy.
DOI: 10.6084/m9.figshare.29134017
title: A lymphostatin homologue from <i>Chlamydia pecorum</i> inhibits mitogen-activated bovine T cell proliferation and IFNγ production

description: Pathogens frequently produce proteins to evade or inhibit host immune responses. One such protein is lymphostatin from attaching and effacing <i>Escherichia coli</i> (also known as lymphocyte inhibitory factor A; LifA), which influences intestinal colonization and inhibits mitogen- and antigen-activated proliferation of T lymphocytes and pro-inflammatory cytokine synthesis. Here, we report the cloning, purification and characterization of a LifA homologue from <i>Chlamydia pecorum</i>. The predicted 382 KDa protein (CPE2_0552) exhibited 36% identity and 55% similarity over 3171 amino acids to lymphostatin from enteropathogenic <i>E. coli</i> strain E2348/69. CPE2_0552 shares glycosyltransferase and cysteine protease motifs required for lymphostatin activity, including similarity in the tertiary structure of these domains predicted by AlphaFold 3. Purified CPE2_0552 did not share the L-shaped globular structure of lymphostatin when analyzed by transmission electron microscopy. CPE2_0552 inhibited concanavalin A-stimulated proliferation of bovine T cells in a concentration-dependent manner, with an inhibitory dose 50 (ID<sub>50</sub>) of 812 pg/mL. This was 38-fold higher than the ID<sub>50</sub> of <i>E. coli</i> E2348/69 lymphostatin tested in parallel on T cells from the same donors (21 pg/mL), but was similar to another LifA homologue from <i>E. coli</i> O157:H7 (ToxB). Moreover, CPE2_0552 inhibited the secretion of interferon gamma (IFNγ), a key cytokine that influences the outcome of <i>Chlamydia</i> infections. At the concentrations at which CPE2_0552 inhibited T lymphocyte proliferation and IFNγ secretion, negligible cytotoxicity was observed after 72 h of stimulation. Our study indicates that <i>E. coli</i> lymphostatin belongs to a wider family of lymphocyte-inhibitory molecules that exist in distantly related bacterial pathogens.
DOI: 10.6084/m9.figshare.29134017.v1
title: A lymphostatin homologue from <i>Chlamydia pecorum</i> inhibits mitogen-activated bovine T cell proliferation and IFNγ production

description: Pathogens frequently produce proteins to evade or inhibit host immune responses. One such protein is lymphostatin from attaching and effacing <i>Escherichia coli</i> (also known as lymphocyte inhibitory factor A; LifA), which influences intestinal colonization and inhibits mitogen- and antigen-activated proliferation of T lymphocytes and pro-inflammatory cytokine synthesis. Here, we report the cloning, purification and characterization of a LifA homologue from <i>Chlamydia pecorum</i>. The predicted 382 KDa protein (CPE2_0552) exhibited 36% identity and 55% similarity over 3171 amino acids to lymphostatin from enteropathogenic <i>E. coli</i> strain E2348/69. CPE2_0552 shares glycosyltransferase and cysteine protease motifs required for lymphostatin activity, including similarity in the tertiary structure of these domains predicted by AlphaFold 3. Purified CPE2_0552 did not share the L-shaped globular structure of lymphostatin when analyzed by transmission electron microscopy. CPE2_0552 inhibited concanavalin A-stimulated proliferation of bovine T cells in a concentration-dependent manner, with an inhibitory dose 50 (ID<sub>50</sub>) of 812 pg/mL. This was 38-fold higher than the ID<sub>50</sub> of <i>E. coli</i> E2348/69 lymphostatin tested in parallel on T cells from the same donors (21 pg/mL), but was similar to another LifA homologue from <i>E. coli</i> O157:H7 (ToxB). Moreover, CPE2_0552 inhibited the secretion of interferon gamma (IFNγ), a key cytokine that influences the outcome of <i>Chlamydia</i> infections. At the concentrations at which CPE2_0552 inhibited T lymphocyte proliferation and IFNγ secretion, negligible cytotoxicity was observed after 72 h of stimulation. Our study indicates that <i>E. coli</i> lymphostatin belongs to a wider family of lymphocyte-inhibitory molecules that exist in distantly related bacterial pathogens.
DOI: 10.6084/m9.figshare.30460195
title: Detection of <i>Clostridium sporogenes</i> in a Roman-era cattle mass grave at Vilauba

description: In the ancient Roman world, cattle played an integral role in daily agricultural tasks, providing the means necessary to plow fields, mill grains, and transport goods. The research presented here deals with the remains of 14 cattle discovered in a mass grave at the Roman villa of Vilauba in Catalonia, Spain. According to the archaeological record, it can be ruled out that the animals were slaughtered for consumption, banqueting, or sacrificial purposes. By investigating the metagenomic sequences generated from the bovine remains, we identified in three individuals a group I <i>Clostridium</i> strain, phylogenetically related to known producers of botulinum neurotoxins – suggesting that the Vilauba strain may have had toxigenic potential. Moreover, we discovered a <i>Mycolicibacterium</i> species phylogenetically related to known opportunistic pathogens. While no definitive conclusions can be drawn about disease, the phylogenetic placement of these taxa and the detection of <i>Clostridium</i> virulence-associated genes suggest a possible role beyond postmortem contamination. Collectively, these findings draw attention to atypical bacterial species, such as <i>C. sporogenes</i>, which are often overlooked in palaeogenomic studies due to their ambiguous status as environmental microbes, commensals, or potential pathogens. Their detection in animal remains highlights that they may represent a blind spot in our current understanding of livestock health. More broadly, this study underscores the current complexity of investigating such taxa and emphasizes the need for novel methods to disentangle the roles of these bacterial species.
DOI: 10.6084/m9.figshare.30460195.v1
title: Detection of <i>Clostridium sporogenes</i> in a Roman-era cattle mass grave at Vilauba

description: In the ancient Roman world, cattle played an integral role in daily agricultural tasks, providing the means necessary to plow fields, mill grains, and transport goods. The research presented here deals with the remains of 14 cattle discovered in a mass grave at the Roman villa of Vilauba in Catalonia, Spain. According to the archaeological record, it can be ruled out that the animals were slaughtered for consumption, banqueting, or sacrificial purposes. By investigating the metagenomic sequences generated from the bovine remains, we identified in three individuals a group I <i>Clostridium</i> strain, phylogenetically related to known producers of botulinum neurotoxins – suggesting that the Vilauba strain may have had toxigenic potential. Moreover, we discovered a <i>Mycolicibacterium</i> species phylogenetically related to known opportunistic pathogens. While no definitive conclusions can be drawn about disease, the phylogenetic placement of these taxa and the detection of <i>Clostridium</i> virulence-associated genes suggest a possible role beyond postmortem contamination. Collectively, these findings draw attention to atypical bacterial species, such as <i>C. sporogenes</i>, which are often overlooked in palaeogenomic studies due to their ambiguous status as environmental microbes, commensals, or potential pathogens. Their detection in animal remains highlights that they may represent a blind spot in our current understanding of livestock health. More broadly, this study underscores the current complexity of investigating such taxa and emphasizes the need for novel methods to disentangle the roles of these bacterial species.
DOI: 10.6084/m9.figshare.28531617
title: Exploring the causal role of pathogen-derived antibodies in major urinary and kidney diseases: Insights from generalized summary data-based Mendelian randomization

description: Chronic kidney and urinary tract diseases, including glomerulonephritis, nephrotic syndrome, and chronic kidney disease (CKD), present significant global health challenges. Recent studies suggest a complex interplay between infectious pathogens and immune-mediated kidney damage. This study employs Generalized Summary data-based Mendelian Randomization (GSMR) to explore causal relationships between pathogen-derived antibodies and major urinary and kidney diseases.We conducted a two-sample MR analysis using summary statistics from large-scale Genome-Wide Association Studies (GWAS) to assess associations between 46 pathogen-specific antibodies and seven urinary system diseases. We utilized robust statistical methods, including inverse variance weighting, to ascertain causal effects while controlling for potential confounders.Significant associations were identified between several pathogen-specific antibodies and disease risk. Notably, Epstein-Barr virus (EBNA-1) antibody levels were inversely associated with glomerulonephritis and nephrotic syndrome, indicating a potential protective effect. Conversely, Anti-Merkel cell polyomavirus IgG seropositivity was linked to increased risks of CKD and glomerulonephritis. Additionally, immune-mediated mechanisms were highlighted, with certain antibodies exhibiting dual roles as risk factors or protective agents.This study underscores the complex role of pathogen antibodies in the pathogenesis of kidney and urinary tract diseases, revealing significant implications for future research and potential therapeutic strategies. The findings advocate for further investigation into specific pathogen interactions with the immune system, aiming to inform targeted interventions.