cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.27930868.v1
title: <i>Peptostreptococcus Anaerobius</i> enhances dextran sulfate sodium-induced colitis by promoting nf-κB-NLRP3-Dependent macrophage pyroptosis

description: Evidence indicates that gut microbiota is crucial in ulcerative colitis (UC) development. Increased <i>Peptostreptococcus</i> species abundance is linked to UC, but its role and mechanisms in intestinal inflammation are not well understood. This study used a dextran sulfate sodium (DSS)-induced colitis model in mice, and different bacterial strains were administered via gavage. We assessed clinical manifestations, colonic barrier function, gut microbiota composition, and levels of inflammatory cytokines, NOD-like receptor family pyrin domain-containing 3 (NLRP3) signaling molecules, and pyroptosis-related proteins. Mouse bone marrow-derived macrophages (BMDMs) were infected with <i>Peptostreptococcus anaerobius</i> at different time points and multiplicities of infection (MOI). Cell viability and the expression of NLRP3 signaling molecules and pyroptosis-associated proteins were assessed. The inhibitors C29, TAK-242, and MCC950 were employed for Toll-like receptor (TLR) and NLRP3 signaling pathways. It was observed that <i>P. anaerobius</i> exacerbated intestinal inflammation and barrier injury in DSS-induced colitis in mice. Additionally, <i>P. anaerobius</i> contributed to gut microbiota dysbiosis during colitis progression. <i>P. anaerobius</i> induced the expression of NLRP3 signaling molecules and pyroptosis-associated proteins in mouse colitis tissues. <i>In vitro</i> assays demonstrated that <i>P. anaerobius</i> activated NLRP3 inflammasome and evoked gasdermin D-mediated pyroptosis and interleukin (IL)-1β secretion in macrophages. Furthermore, TLR2 and TLR4 were identified as key mediators of <i>P. anaerobius</i>-induced macrophage pyroptosis via activation of the Nuclear Factor-kappa B (NF-κB)-NLRP3 pathway. In conclusion, <i>P. anaerobius</i> promotes macrophage pyroptosis and IL-1β secretion through the TLR2/4-NF-κB-NLRP3 signaling axis, thereby aggravating colitis. <i>P. anaerobius</i> may represent a potential risk factor for UC development.
DOI: 10.6084/m9.figshare.26954704.v1
title: Human tetraspanin CD81 facilitates invasion of <i>Salmonella enterica</i> into human epithelial cells

description: Human CD81 and CD9 are members of the tetraspanin family of proteins characterized by a canonical structure of four transmembrane domains and two extracellular loop domains. Tetraspanins are known as molecular facilitators, which assemble and organize cell surface receptors and partner molecules forming clusters known as tetraspanin-enriched microdomains. They have been implicated to play various biological roles including an involvement in infections with microbial pathogens. Here, we demonstrate an important role of CD81 for the invasion of epithelial cells by <i>Salmonella enterica</i>. We show that overexpression of CD81 in HepG2 cells enhances invasion of various typhoidal and non-typhoidal <i>Salmonella</i> serovars. Deletion of CD81 by CRISPR/Cas9 in intestinal epithelial cells (C2BBe1 and HT29-MTX-E12) reduces <i>S</i>. Typhimurium invasion. In addition, the effect of human CD81 is species-specific as only human but not rat CD81 facilitates <i>Salmonella</i> invasion. Finally, immunofluorescence microscopy and proximity ligation assay revealed that both human tetraspanins CD81 and CD9 are recruited to the entry site of <i>S</i>. Typhimurium during invasion but not during adhesion to the host cell surface. Overall, we demonstrate that the human tetraspanin CD81 facilitates <i>Salmonella</i> invasion into epithelial host cells.
DOI: 10.6084/m9.figshare.27232377
title: Unveiling the roles of <i>CaSDH8</i> in <i>Candida albicans</i>: Implications for virulence and azole resistance

description: <i>Candida albicans</i> is the most common pathogen in systemic fungal diseases, exhibits a complex pathogenic mechanism, and is increasingly becoming drug tolerant. Therefore, it is particularly important to study the genes associated with virulence and resistance of <i>C. albicans</i>. Here, we identified a gene (<i>orf19.1588</i>) that encodes a conserved mitochondrial protein known as <i>CaSDH8</i>, upon deletion of <i>CaSdh8</i>, the deleted strain (<i>Casdh8Δ/Δ</i>) experienced impaired growth, hyphal development, and virulence. <i>Casdh8Δ/Δ</i> displayed a reduced capacity to utilize alternative carbon sources, along with detrimental alterations in reactive oxygen species (ROS), mitochondrial membrane potential (MMP) depolarization, and adenosine triphosphate (ATP) levels. Interestingly, <i>Casdh8Δ/Δ</i> demonstrated resistance to azole drugs, and under the influence of fluconazole, the cell membrane permeability and mitochondrial function of <i>Casdh8Δ/Δ</i> were less compromised than those of the wild type, indicating a reduction in the detrimental effects of fluconazole on <i>Casdh8Δ/Δ</i>. These findings highlight the significance of <i>CaSDH8</i> as a crucial gene for the maintenance of cellular homoeostasis. Our study is the first to document the effects of the <i>CaSDH8</i> gene on the virulence and azole resistance of <i>C. albicans</i> at both the molecular and animal levels, providing new clues and directions for the antifungal infection and the discovery of antifungal drug targets.
DOI: 10.6084/m9.figshare.27232377.v1
title: Unveiling the roles of <i>CaSDH8</i> in <i>Candida albicans</i>: Implications for virulence and azole resistance

description: <i>Candida albicans</i> is the most common pathogen in systemic fungal diseases, exhibits a complex pathogenic mechanism, and is increasingly becoming drug tolerant. Therefore, it is particularly important to study the genes associated with virulence and resistance of <i>C. albicans</i>. Here, we identified a gene (<i>orf19.1588</i>) that encodes a conserved mitochondrial protein known as <i>CaSDH8</i>, upon deletion of <i>CaSdh8</i>, the deleted strain (<i>Casdh8Δ/Δ</i>) experienced impaired growth, hyphal development, and virulence. <i>Casdh8Δ/Δ</i> displayed a reduced capacity to utilize alternative carbon sources, along with detrimental alterations in reactive oxygen species (ROS), mitochondrial membrane potential (MMP) depolarization, and adenosine triphosphate (ATP) levels. Interestingly, <i>Casdh8Δ/Δ</i> demonstrated resistance to azole drugs, and under the influence of fluconazole, the cell membrane permeability and mitochondrial function of <i>Casdh8Δ/Δ</i> were less compromised than those of the wild type, indicating a reduction in the detrimental effects of fluconazole on <i>Casdh8Δ/Δ</i>. These findings highlight the significance of <i>CaSDH8</i> as a crucial gene for the maintenance of cellular homoeostasis. Our study is the first to document the effects of the <i>CaSDH8</i> gene on the virulence and azole resistance of <i>C. albicans</i> at both the molecular and animal levels, providing new clues and directions for the antifungal infection and the discovery of antifungal drug targets.
DOI: 10.6084/m9.figshare.27089608
title: Hepatic and extrahepatic metabolic modulation in hbv-related decompensated cirrhosis and acute-on-chronic liver failure

description: Acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) are life-threatening syndromes that can develop at the end-stage of chronic hepatitis B virus (HBV) infection. Both ACLF and DC are complicated by hepatic and extrahepatic pathogeneses. To better understand the compartment-specific metabolic modulations related to their pathogenesis, HBV-DC, HBV-ACLF patients, and controls (30 each) were analyzed by metabolomics using portal (Port), hepatic vein (Hep), and peripheral (Peri) serum. Compartment ratios of metabolites (Ratio<sub>Hep/Port</sub>, Ratio<sub>Peri/Hep</sub>, and Ratio<sub>Port/Peri</sub>) were calculated. The liver tissues (10 per group) were analyzed using transcriptomics and metabolomics. An additional 75 patients with ACLF, 20 with DC, and 20 with liver cirrhosis (LC) were used to confirm oxlipid dysregulation. Both multi-omics datasets suggest suppressed energy, amino acid, and pyrimidine metabolism in the ACLF/DC liver. The serum metabolomic variations were contributed primarily by disease rather than sampling compartments, as both HBV-ACLF and HBV-DC patients demonstrated abnormal profiles of amino acids and peptides, indoles, purines, steroids, and benzimidazoles. In ACLF/DC patients, impaired hepatic metabolism resulted in a highly correlated hepatic and portal vein serum metabolome and release of inflammatory lipids and heme metabolites from the liver. HBV-ACLF showed higher Ratio<sub>Peri/Hep</sub> of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher Ratio<sub>Port/Peri</sub> of gut microbial metabolites. An inflammatory oxlipid outburst was confirmed in the early stages of HBV-ACLF. The inflammatory effects of the selected oxlipids were confirmed in monocytes. These findings support a synergy between liver-specific mechanisms and systemic inflammation in ACLF/DC development, and that pro-inflammatory oxlipids are metabolic signatures of early HBV-ACLF.
DOI: 10.6084/m9.figshare.27089608.v1
title: Hepatic and extrahepatic metabolic modulation in hbv-related decompensated cirrhosis and acute-on-chronic liver failure

description: Acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) are life-threatening syndromes that can develop at the end-stage of chronic hepatitis B virus (HBV) infection. Both ACLF and DC are complicated by hepatic and extrahepatic pathogeneses. To better understand the compartment-specific metabolic modulations related to their pathogenesis, HBV-DC, HBV-ACLF patients, and controls (30 each) were analyzed by metabolomics using portal (Port), hepatic vein (Hep), and peripheral (Peri) serum. Compartment ratios of metabolites (Ratio<sub>Hep/Port</sub>, Ratio<sub>Peri/Hep</sub>, and Ratio<sub>Port/Peri</sub>) were calculated. The liver tissues (10 per group) were analyzed using transcriptomics and metabolomics. An additional 75 patients with ACLF, 20 with DC, and 20 with liver cirrhosis (LC) were used to confirm oxlipid dysregulation. Both multi-omics datasets suggest suppressed energy, amino acid, and pyrimidine metabolism in the ACLF/DC liver. The serum metabolomic variations were contributed primarily by disease rather than sampling compartments, as both HBV-ACLF and HBV-DC patients demonstrated abnormal profiles of amino acids and peptides, indoles, purines, steroids, and benzimidazoles. In ACLF/DC patients, impaired hepatic metabolism resulted in a highly correlated hepatic and portal vein serum metabolome and release of inflammatory lipids and heme metabolites from the liver. HBV-ACLF showed higher Ratio<sub>Peri/Hep</sub> of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher Ratio<sub>Port/Peri</sub> of gut microbial metabolites. An inflammatory oxlipid outburst was confirmed in the early stages of HBV-ACLF. The inflammatory effects of the selected oxlipids were confirmed in monocytes. These findings support a synergy between liver-specific mechanisms and systemic inflammation in ACLF/DC development, and that pro-inflammatory oxlipids are metabolic signatures of early HBV-ACLF.
DOI: 10.6084/m9.figshare.27308844.v1
title: Epigenetic modification of hepatitis B virus infection and related hepatocellular carcinoma

description: Hepatitis B virus (HBV) infection poses a challenge to global public health. Persistent liver infection with HBV is associated with an increased risk of developing severe liver disease. The complex interaction between the virus and the host is the reason for the persistent presence of HBV and the risk of tumour development. Chronic liver inflammation, integration of viral genome with host genome, expression of HBx protein, and viral genotype are all key participants in the pathogenesis of hepatocellular carcinoma (HCC). Epigenetic regulation in HBV-associated HCC involves complex interactions of molecular mechanisms that control gene expression and function without altering the underlying DNA sequence. These epigenetic modifications can significantly affect the onset and progression of HCC. This review summarizes recent research on the epigenetic regulation of HBV persistent infection and HBV-HCC development, including DNA methylation, histone modification, RNA modification, non-coding RNA, etc. Enhanced knowledge of these mechanisms will offer fresh perspectives and potential targets for intervention tactics in HBV-HCC.
DOI: 10.6084/m9.figshare.27925962
title: Immunization with the NcMYR1 gene knockout strain effectively protected C57BL/6 mice and their pups against the <i>Neospora caninum</i> challenge

description: <i>Neospora caninum</i> is an important protozoan parasite that causes abortion in cattle and nervous system dysfunction in dogs. No effective drugs and vaccines for neosporosis are available. Further elucidation of proteins related to <i>N. caninum</i> virulence will provide potential candidates for vaccine development against neosporosis. In the present study, <i>N. caninum</i> c-Myc regulatory protein (NcMYR1) gene knockout strains (ΔNcMYR1-1, ΔNcMYR1-2, and ΔNcMYR1-3) were generated using the CRISPR-Cas9 gene editing system to investigate phenotype changes and the potential of the ΔNcMYR1-1 strain as an attenuated vaccine, and this is the first time of using the <i>N. caninum</i> CRISPR-Cas9 gene knockout strain as an attenuated vaccine. NcMYR1 was determined to be a cytoplasmic protein in <i>N. caninum</i> tachyzoites. The deficiency of NcMYR1 decreased the plaque area and the rate of invasion, replication, and egression of the parasites. ΔNcMYR1-1 strain-infected C57BL/6 mice had 100% survival rate, reduced parasite burden, and alleviated pathological changes in tissues compared with those in Nc-1 strain-infected mice. Immunization with ΔNcMYR1-1 tachyzoites increased the productions of cytokines in mice, with a survival rate reaching 80%, and the parasite burdens in the liver and spleen were greatly reduced when challenged with the Nc-1 strain with a lethal dose after 40 days of ΔNcMYR1-1 tachyzoite immunization. ΔNcMYR1 immunization could decrease the abortion rate of female mice from 71.4% to 12.5% and increase the survival rate of pups from 12.5% to 83.3% against the <i>N. caninum</i> challenge. Above all, NcMYR1 is a virulence factor and the ΔNcMYR1-1 strain could be used as a candidate vaccine against <i>N. caninum</i> infection and vertical transmission. <i>Neospora caninum</i> is an intracellular parasite that causes abortion, stillbirth, and mummified fetuses in cows; the key strategy for the prevention of <i>N. caninum</i> is vaccine; and the study of the virulence gene of <i>N. caninum</i> is key to developing effective vaccines against neosporosis. NcMYR1 is critical for the processes of growth, invasion, and replication and is a virulence factor in <i>N. caninum</i>. The ΔNcMYR1-1 strain could provide an effective protection against <i>N. caninum</i> infection and increase the abortion rate of mice and the survival rate of pups, indicating that the ΔNcMYR1-1 strain may be a promising vaccine candidate for neosporosis, which lays a theoretical foundation for the prevention of neosporosis.
DOI: 10.6084/m9.figshare.27925962.v1
title: Immunization with the NcMYR1 gene knockout strain effectively protected C57BL/6 mice and their pups against the <i>Neospora caninum</i> challenge

description: <i>Neospora caninum</i> is an important protozoan parasite that causes abortion in cattle and nervous system dysfunction in dogs. No effective drugs and vaccines for neosporosis are available. Further elucidation of proteins related to <i>N. caninum</i> virulence will provide potential candidates for vaccine development against neosporosis. In the present study, <i>N. caninum</i> c-Myc regulatory protein (NcMYR1) gene knockout strains (ΔNcMYR1-1, ΔNcMYR1-2, and ΔNcMYR1-3) were generated using the CRISPR-Cas9 gene editing system to investigate phenotype changes and the potential of the ΔNcMYR1-1 strain as an attenuated vaccine, and this is the first time of using the <i>N. caninum</i> CRISPR-Cas9 gene knockout strain as an attenuated vaccine. NcMYR1 was determined to be a cytoplasmic protein in <i>N. caninum</i> tachyzoites. The deficiency of NcMYR1 decreased the plaque area and the rate of invasion, replication, and egression of the parasites. ΔNcMYR1-1 strain-infected C57BL/6 mice had 100% survival rate, reduced parasite burden, and alleviated pathological changes in tissues compared with those in Nc-1 strain-infected mice. Immunization with ΔNcMYR1-1 tachyzoites increased the productions of cytokines in mice, with a survival rate reaching 80%, and the parasite burdens in the liver and spleen were greatly reduced when challenged with the Nc-1 strain with a lethal dose after 40 days of ΔNcMYR1-1 tachyzoite immunization. ΔNcMYR1 immunization could decrease the abortion rate of female mice from 71.4% to 12.5% and increase the survival rate of pups from 12.5% to 83.3% against the <i>N. caninum</i> challenge. Above all, NcMYR1 is a virulence factor and the ΔNcMYR1-1 strain could be used as a candidate vaccine against <i>N. caninum</i> infection and vertical transmission. <i>Neospora caninum</i> is an intracellular parasite that causes abortion, stillbirth, and mummified fetuses in cows; the key strategy for the prevention of <i>N. caninum</i> is vaccine; and the study of the virulence gene of <i>N. caninum</i> is key to developing effective vaccines against neosporosis. NcMYR1 is critical for the processes of growth, invasion, and replication and is a virulence factor in <i>N. caninum</i>. The ΔNcMYR1-1 strain could provide an effective protection against <i>N. caninum</i> infection and increase the abortion rate of mice and the survival rate of pups, indicating that the ΔNcMYR1-1 strain may be a promising vaccine candidate for neosporosis, which lays a theoretical foundation for the prevention of neosporosis.
DOI: 10.6084/m9.figshare.26936154
title: YjbH contributes to <i>Staphylococcus aureus</i> skin pathology and immune response through Agr-mediated α-toxin regulation

description: <i>Staphylococcus aureus</i> is the most common cause of skin and soft tissue infections (SSTIs) with Methicillin-Resistant <i>S. aureus</i> (MRSA) strains being a major contributor in both community and hospital settings. <i>S. aureus</i> relies on metabolic diversity and a large repertoire of virulence factors to cause disease. This includes α-hemolysin (Hla), an integral player in tissue damage found in various models, including SSTIs. Previously, we identified a role for the Spx adapter protein, YjbH, in the regulation of several virulence factors and as an inhibitor of pathogenesis in a sepsis model. In this study, we found that YjbH is critical for tissue damage during SSTI, and its absence leads to decreased proinflammatory chemokines and cytokines in the skin. We identified no contribution of YjbI, encoded on the same transcript as YjbH. Using a combination of reporters and quantitative hemolysis assays, we demonstrated that YjbH impacts Hla expression and activity both <i>in vitro</i> and <i>in vivo</i>. Additionally, expression of Hla from a non-native promoter reversed the tissue damage phenotype of the Δ<i>yjbIH</i> mutant. Lastly, we identified reduced Agr activity as the likely cause for reduced Hla production in the Δ<i>yjbH</i> mutant. This work continues to define the importance of YjbH in the pathogenesis of <i>S. aureus</i> infection as well as identify a new pathway important for Hla production.
DOI: 10.6084/m9.figshare.26936154.v3
title: YjbH contributes to <i>Staphylococcus aureus</i> skin pathology and immune response through Agr-mediated α-toxin regulation

description: <i>Staphylococcus aureus</i> is the most common cause of skin and soft tissue infections (SSTIs) with Methicillin-Resistant <i>S. aureus</i> (MRSA) strains being a major contributor in both community and hospital settings. <i>S. aureus</i> relies on metabolic diversity and a large repertoire of virulence factors to cause disease. This includes α-hemolysin (Hla), an integral player in tissue damage found in various models, including SSTIs. Previously, we identified a role for the Spx adapter protein, YjbH, in the regulation of several virulence factors and as an inhibitor of pathogenesis in a sepsis model. In this study, we found that YjbH is critical for tissue damage during SSTI, and its absence leads to decreased proinflammatory chemokines and cytokines in the skin. We identified no contribution of YjbI, encoded on the same transcript as YjbH. Using a combination of reporters and quantitative hemolysis assays, we demonstrated that YjbH impacts Hla expression and activity both <i>in vitro</i> and <i>in vivo</i>. Additionally, expression of Hla from a non-native promoter reversed the tissue damage phenotype of the Δ<i>yjbIH</i> mutant. Lastly, we identified reduced Agr activity as the likely cause for reduced Hla production in the Δ<i>yjbH</i> mutant. This work continues to define the importance of YjbH in the pathogenesis of <i>S. aureus</i> infection as well as identify a new pathway important for Hla production.
DOI: 10.6084/m9.figshare.27888075
title: DNA damage repair factor Rad18 controls virulence partially via transcriptional suppression of genes <i>HWP1</i> and <i>ECE1</i> in <i>Candida albicans</i>

description: DNA damage repair is a crucial cellular mechanism for rectifying DNA lesions arising during growth and development. Among the various repair pathways, postreplication repair (PRR) plays a pivotal role in resolving single-stranded gaps induced by DNA damage. However, the contribution of PRR to virulence remains elusive in the fungal pathogen <i>Candida albicans (C. albicans)</i>. In this study, we investigated the role of Rad18, a critical component of PRR, in DNA damage response and virulence in <i>C. albicans</i>. We observed that deletion of <i>RAD18</i> in <i>C. albicans</i> resulted in heightened sensitivity to DNA damage stress. Through deletion of specific internal domains coupled with spot assay analysis, we show that the internal RING and SAP domains play essential roles in DNA damage response, whereas the ZNF domain was less important. Surprisingly, the lack of Rad18 in <i>C. albicans</i> resulted in heightened intracellular survival within macrophages and elevated virulence in the <i>Galleria mellonella</i> model. RNAseq analysis revealed that loss of Rad18 upregulated the transcription of genes encoding transporters and oxidoreductases, as well as virulence genes, including <i>HWP1</i> and <i>ECE1</i>. Suppression of the transcription of these virulence genes in the <i>RAD18</i> deletion strain by a dCas9-mediated CRISPRi system reversed this increased virulence. Taken together, these data demonstrate that Rad18 plays a significant role in virulence partially through transcriptional suppression of virulence genes <i>HWP1</i> and <i>ECE1</i> in <i>C. albicans</i>. Our findings provide valuable insights into the intricate relationship between DNA damage response and virulence in <i>C. albicans</i>.