cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.21173890.v1
title: Intracellular bacteriolysis contributes to pathogenicity of <i>Staphylococcus aureus</i> by exacerbating AIM2-mediated inflammation and necroptosis

description: <i>Staphylococcus aureus</i> can survive within phagocytes. Indeed, we confirm in this study that approximately 10% of population persists in macrophages during <i>S. aureus</i> infection, while the rest are eliminated due to bacteriolysis, which is of particular interest to us. Herein, we observe that the bacteriolysis is an early event accompanied by macrophage death during <i>S. aureus</i> infection. Furthermore, the cell death is significantly accelerated following increased intracellular bacteriolysis, indicating that intracellular bacteriolysis induces cell death. Subsequently, we establish that the cell death is not apoptosis or pyroptosis, but AIM2-mediated necroptosis, accompanied by AIM2 inflammasome activation. This finding challenges the classical model that the cell death that accompanies inflammasome activation is always pyroptosis. In addition, we observe that the apoptosis-associated genes are highly inhibited during <i>S. aureus</i> infection. Finally, we establish in vivo that increased bacteriolysis significantly enhances <i>S. aureus</i> pathogenicity by promoting its dissemination to kidney and leading to an inflammatory cytokine storm in AIM2-mediated manner. Collectively, our data demonstrate that bacteriolysis is detrimental when triggered in excess and its side effect is mediated by AIM2. Meanwhile, we propose a potential immune manipulation strategy by which <i>S. aureus</i> sacrifices the minority to trigger a limited necroptosis, thereby releasing signals from dead cells to inhibit apoptosis and other anti-inflammatory cascades of live cells, eventually surviving within host cells and establishing infection.
DOI: 10.6084/m9.figshare.19941580
title: <i>Talaromyces marneffei</i> activates the AIM2-caspase-1/-4-GSDMD axis to induce pyroptosis in hepatocytes

description: <i>Talaromyces marneffei</i> tends to induce systemic infection in immunocompromised individuals, which is one of the causes of the high mortality. The underlying molecular mechanisms of <i>T.marneffei</i>-induced abnormal liver function are still poorly understood. In this study, we found that <i>T.marneffei</i>-infected patients could develop abnormal liver function, evidenced by reduced albumin and increased levels of aspartate aminotransferase (AST) and AST/alanine aminotransferase (ALT). <i>T. marneffei</i>-infected mice exhibited similar characteristics. <i>In vitro</i> investigations showed that <i>T.marneffei</i> induced the death of AML-12 cells. Furthermore, we determined that <i>T.marneffei</i> infection induced pyroptosis in hepatocytes of C57BL/6J mice and AML-12 cells, demonstrated by the increase of AIM2, caspase-1/-4, Gasdermin D(GSDMD) and pyroptosis-related cytokines in <i>T.marneffei</i>-infected mice/cells. Importantly, cell death was markedly suppressed in the presence of VX765 (an inhibitor of caspase-1/-4). Furthermore, in the presence of VX765, <i>T.marneffei</i>-induced pyroptosis was blocked. Nevertheless, necroptosis and apoptosis were also detected in infected animal model at 14 days post-infection. In conclusion, <i>T.marneffei</i> induces pyroptosis in hepatocytes through activation of the AIM2-caspase-1/-4-GSDMD axis, which may be an important cause of liver damage, and other death pathways including necroptosis and apoptosis may also be involved in the later stage of infection.
DOI: 10.6084/m9.figshare.19941580.v1
title: <i>Talaromyces marneffei</i> activates the AIM2-caspase-1/-4-GSDMD axis to induce pyroptosis in hepatocytes

description: <i>Talaromyces marneffei</i> tends to induce systemic infection in immunocompromised individuals, which is one of the causes of the high mortality. The underlying molecular mechanisms of <i>T.marneffei</i>-induced abnormal liver function are still poorly understood. In this study, we found that <i>T.marneffei</i>-infected patients could develop abnormal liver function, evidenced by reduced albumin and increased levels of aspartate aminotransferase (AST) and AST/alanine aminotransferase (ALT). <i>T. marneffei</i>-infected mice exhibited similar characteristics. <i>In vitro</i> investigations showed that <i>T.marneffei</i> induced the death of AML-12 cells. Furthermore, we determined that <i>T.marneffei</i> infection induced pyroptosis in hepatocytes of C57BL/6J mice and AML-12 cells, demonstrated by the increase of AIM2, caspase-1/-4, Gasdermin D(GSDMD) and pyroptosis-related cytokines in <i>T.marneffei</i>-infected mice/cells. Importantly, cell death was markedly suppressed in the presence of VX765 (an inhibitor of caspase-1/-4). Furthermore, in the presence of VX765, <i>T.marneffei</i>-induced pyroptosis was blocked. Nevertheless, necroptosis and apoptosis were also detected in infected animal model at 14 days post-infection. In conclusion, <i>T.marneffei</i> induces pyroptosis in hepatocytes through activation of the AIM2-caspase-1/-4-GSDMD axis, which may be an important cause of liver damage, and other death pathways including necroptosis and apoptosis may also be involved in the later stage of infection.
DOI: 10.6084/m9.figshare.21173890
title: Intracellular bacteriolysis contributes to pathogenicity of <i>Staphylococcus aureus</i> by exacerbating AIM2-mediated inflammation and necroptosis

description: <i>Staphylococcus aureus</i> can survive within phagocytes. Indeed, we confirm in this study that approximately 10% of population persists in macrophages during <i>S. aureus</i> infection, while the rest are eliminated due to bacteriolysis, which is of particular interest to us. Herein, we observe that the bacteriolysis is an early event accompanied by macrophage death during <i>S. aureus</i> infection. Furthermore, the cell death is significantly accelerated following increased intracellular bacteriolysis, indicating that intracellular bacteriolysis induces cell death. Subsequently, we establish that the cell death is not apoptosis or pyroptosis, but AIM2-mediated necroptosis, accompanied by AIM2 inflammasome activation. This finding challenges the classical model that the cell death that accompanies inflammasome activation is always pyroptosis. In addition, we observe that the apoptosis-associated genes are highly inhibited during <i>S. aureus</i> infection. Finally, we establish in vivo that increased bacteriolysis significantly enhances <i>S. aureus</i> pathogenicity by promoting its dissemination to kidney and leading to an inflammatory cytokine storm in AIM2-mediated manner. Collectively, our data demonstrate that bacteriolysis is detrimental when triggered in excess and its side effect is mediated by AIM2. Meanwhile, we propose a potential immune manipulation strategy by which <i>S. aureus</i> sacrifices the minority to trigger a limited necroptosis, thereby releasing signals from dead cells to inhibit apoptosis and other anti-inflammatory cascades of live cells, eventually surviving within host cells and establishing infection.
DOI: 10.6084/m9.figshare.20629443
title: A nucleic acid detection assay combining reverse transcription recombinase-aided amplification with a lateral flow dipstick for the rapid visual detection of porcine deltacoronavirus

description: Porcine deltacoronavirus (PDCoV) is an emerging enteropathogen causing severe diarrhoea, dehydration, and death in nursing piglets and enormous economic losses for the global swine industry. Furthermore, it can infect multiple animal species including humans. Therefore, a rapid, definitive diagnostic assay is required for the effective control of this zoonotic pathogen. To identify PDCoV, we developed a nucleic acid detection assay combining reverse transcription recombinase-aided amplification (RT-RAA) with a lateral flow dipstick (LFD) targeting the highly conserved genomic region in the <i>ORF1b</i> gene. The RT-RAA-LFD assay exhibited good PDCoV detection reproducibility and repeatability and could be completed within 11 min. Ten minutes at 40 °C was required for nucleic acid amplification and 1 min at room temperature was needed for the visual LFD readout. The assay specifically detected PDCoV and did not cross-react with any other major swine pathogens. The 95% limit of detection (LOD) was 3.97 median tissue culture infectious dose PDCoV RNA per reaction. This performance was comparable to that of a reference TaqMan-based real-time RT-PCR (trRT-PCR) assay for PDCoV. Of 149 swine small intestine, rectal swab, and serum samples, 71 and 75 tested positive for PDCoV according to RT-RAA-LFD and trRT-PCR, respectively. The diagnostic coincidence rate for both assays was 97.32% (145/149) and the kappa value was 0.946 (p &lt; 0.001). Overall, the RT-RAA-LFD assay is a user-friendly diagnostic tool that can rapidly and visually detect PDCoV.
DOI: 10.6084/m9.figshare.20629443.v1
title: A nucleic acid detection assay combining reverse transcription recombinase-aided amplification with a lateral flow dipstick for the rapid visual detection of porcine deltacoronavirus

description: Porcine deltacoronavirus (PDCoV) is an emerging enteropathogen causing severe diarrhoea, dehydration, and death in nursing piglets and enormous economic losses for the global swine industry. Furthermore, it can infect multiple animal species including humans. Therefore, a rapid, definitive diagnostic assay is required for the effective control of this zoonotic pathogen. To identify PDCoV, we developed a nucleic acid detection assay combining reverse transcription recombinase-aided amplification (RT-RAA) with a lateral flow dipstick (LFD) targeting the highly conserved genomic region in the <i>ORF1b</i> gene. The RT-RAA-LFD assay exhibited good PDCoV detection reproducibility and repeatability and could be completed within 11 min. Ten minutes at 40 °C was required for nucleic acid amplification and 1 min at room temperature was needed for the visual LFD readout. The assay specifically detected PDCoV and did not cross-react with any other major swine pathogens. The 95% limit of detection (LOD) was 3.97 median tissue culture infectious dose PDCoV RNA per reaction. This performance was comparable to that of a reference TaqMan-based real-time RT-PCR (trRT-PCR) assay for PDCoV. Of 149 swine small intestine, rectal swab, and serum samples, 71 and 75 tested positive for PDCoV according to RT-RAA-LFD and trRT-PCR, respectively. The diagnostic coincidence rate for both assays was 97.32% (145/149) and the kappa value was 0.946 (p &lt; 0.001). Overall, the RT-RAA-LFD assay is a user-friendly diagnostic tool that can rapidly and visually detect PDCoV.
DOI: 10.6084/m9.figshare.20116028
title: Biomarkers of caspofungin resistance in <i>Candida albicans</i> isolates: A proteomic approach

description: <i>Candida albicans</i> is a clinically important polymorphic fungal pathogen that causes life-threatening invasive infections in immunocompromised patients. Antifungal therapy failure is a substantial clinical problem, due to the emergence of an increasing number of drug-resistant isolates. Caspofungin is a common antifungal drug, often used as first-line therapy that inhibits cell wall β-(1,3)-glucan synthesis. In this work, the cell surface of different echinocandin-resistant <i>C. albicans</i> clinical isolates was compared with sensitive isolates and their responses to echinocandin treatment analyzed. Proteomic analysis detected changes in the repertoire of proteins involved in cell wall organization and maintenance, in drug-resistant strains compared to susceptible isolates and after incubation with caspofungin. Moreover, an interaction network was created from the differential expression results. Our findings suggest drug resistance may involve not only a different cell wall architecture, but also a different response to drugs.
DOI: 10.6084/m9.figshare.20116028.v1
title: Biomarkers of caspofungin resistance in <i>Candida albicans</i> isolates: A proteomic approach

description: <i>Candida albicans</i> is a clinically important polymorphic fungal pathogen that causes life-threatening invasive infections in immunocompromised patients. Antifungal therapy failure is a substantial clinical problem, due to the emergence of an increasing number of drug-resistant isolates. Caspofungin is a common antifungal drug, often used as first-line therapy that inhibits cell wall β-(1,3)-glucan synthesis. In this work, the cell surface of different echinocandin-resistant <i>C. albicans</i> clinical isolates was compared with sensitive isolates and their responses to echinocandin treatment analyzed. Proteomic analysis detected changes in the repertoire of proteins involved in cell wall organization and maintenance, in drug-resistant strains compared to susceptible isolates and after incubation with caspofungin. Moreover, an interaction network was created from the differential expression results. Our findings suggest drug resistance may involve not only a different cell wall architecture, but also a different response to drugs.
DOI: 10.6084/m9.figshare.20381513
title: The SWC4 subunit of the SWR1 chromatin remodeling complex is involved in varying virulence of <i>Metarhizium brunneum</i> isolates offering role of epigenetic regulation of pathogenicity

description: The host – pathogen interaction is a multifactorial process subject to a co-evolutionary arms race consisting of rapid changes in both host and pathogen, controlled at the genetic and epigenetic levels. Previously, we showed intra-species variation in disease progression and pathogenicity in aphids for <i>Metarhizium brunneum</i> isolates MbK and Mb7. Herein, we compared genomic, epigenetic, and metabolomic variations between these isolates and their effects on pathogenicity. Genomic variation could not completely explain the observed differences between the isolates. However, differential N6-adenine methylation (6 mA) and its correlation to reduced expression of the essential SWC4 subunit of SWR1 chromatin-remodelling complex (SWR1-C) led us to hypothesize a role for <i>swc4</i> in the varying pathogenicity. Mutagenesis of the essential <i>swc4</i> gene in MbKisolate resulted in reduction of secondary-metabolite (SM) secretion and impaired virulence in <i>Galleria mellonella</i>. Our results suggest the role of SWC4 in the regulation of SMs and the role of both SWC4 and SWR1-C in virulence of <i>M. brunneum</i> isolates. A better understanding of epigenetic regulation of SM production and secretion in entomopathogenic fungi may enable theirmanipulation for better biocontrol performance, and expand possibilities for environmentally friendly pest control.
DOI: 10.6084/m9.figshare.20381513.v1
title: The SWC4 subunit of the SWR1 chromatin remodeling complex is involved in varying virulence of <i>Metarhizium brunneum</i> isolates offering role of epigenetic regulation of pathogenicity

description: The host – pathogen interaction is a multifactorial process subject to a co-evolutionary arms race consisting of rapid changes in both host and pathogen, controlled at the genetic and epigenetic levels. Previously, we showed intra-species variation in disease progression and pathogenicity in aphids for <i>Metarhizium brunneum</i> isolates MbK and Mb7. Herein, we compared genomic, epigenetic, and metabolomic variations between these isolates and their effects on pathogenicity. Genomic variation could not completely explain the observed differences between the isolates. However, differential N6-adenine methylation (6 mA) and its correlation to reduced expression of the essential SWC4 subunit of SWR1 chromatin-remodelling complex (SWR1-C) led us to hypothesize a role for <i>swc4</i> in the varying pathogenicity. Mutagenesis of the essential <i>swc4</i> gene in MbKisolate resulted in reduction of secondary-metabolite (SM) secretion and impaired virulence in <i>Galleria mellonella</i>. Our results suggest the role of SWC4 in the regulation of SMs and the role of both SWC4 and SWR1-C in virulence of <i>M. brunneum</i> isolates. A better understanding of epigenetic regulation of SM production and secretion in entomopathogenic fungi may enable theirmanipulation for better biocontrol performance, and expand possibilities for environmentally friendly pest control.
DOI: 10.6084/m9.figshare.19673529
title: Reproduction and pathogenesis of short beak and dwarfish syndrome in Cherry Valley Pekin ducks infected with the rescued novel goose parvovirus

description: Since the outbreak of short beak and dwarfish syndrome (SBDS) in Cherry Valley Pekin ducks in China, novel goose parvovirus (NGPV) has been isolated. Till now, little is known about the NGPV pathogenesis toward Cherry Valley Pekin ducks. Besides, due to detection of duck circovirus co-infection in SBDS clinical cases, whether sole NGPV infection can reproduce all the typical symptoms of SBDS remains unclear. In this study, based on the NGPV isolate SDJN19, an infectious plasmid clone pJNm containing the entire SDJN19 genome was constructed. Transfection of pJNm in embryonated duck eggs resulted in generation of the infectious virus carrying the genetic marker, named rJNm. rJNm infection of 2-day-old Cherry Valley Pekin ducks reproduced all the typical signs of SBDS, including beak atrophy, tongue protrusion, and growth retardation. rJNm can infect Cherry Valley Pekin ducks through the horizontal transmission route, and the infected ducks exhibited the characteristic SBDS symptoms. A high level of serum precipitation antibodies (above 5log<sub>2</sub>) were induced in the surviving ducks, however, high viral loads were still detected in the duck organs, suggesting persistent NGPV infection in ducks. By incorporating the homologous Rep1 and VP1 gene from classical GPV, two chimeric viruses rJN-cVP1 and rJN-cRep1 were generated. Duck infection tests revealed that the non-structural protein Rep1 played a crucial role in the NGPV pathogenicity. The present result lays a solid foundation for further exploring how the Rep protein contributes to the NGPV pathogenesis.
DOI: 10.6084/m9.figshare.19673529.v1
title: Reproduction and pathogenesis of short beak and dwarfish syndrome in Cherry Valley Pekin ducks infected with the rescued novel goose parvovirus

description: Since the outbreak of short beak and dwarfish syndrome (SBDS) in Cherry Valley Pekin ducks in China, novel goose parvovirus (NGPV) has been isolated. Till now, little is known about the NGPV pathogenesis toward Cherry Valley Pekin ducks. Besides, due to detection of duck circovirus co-infection in SBDS clinical cases, whether sole NGPV infection can reproduce all the typical symptoms of SBDS remains unclear. In this study, based on the NGPV isolate SDJN19, an infectious plasmid clone pJNm containing the entire SDJN19 genome was constructed. Transfection of pJNm in embryonated duck eggs resulted in generation of the infectious virus carrying the genetic marker, named rJNm. rJNm infection of 2-day-old Cherry Valley Pekin ducks reproduced all the typical signs of SBDS, including beak atrophy, tongue protrusion, and growth retardation. rJNm can infect Cherry Valley Pekin ducks through the horizontal transmission route, and the infected ducks exhibited the characteristic SBDS symptoms. A high level of serum precipitation antibodies (above 5log<sub>2</sub>) were induced in the surviving ducks, however, high viral loads were still detected in the duck organs, suggesting persistent NGPV infection in ducks. By incorporating the homologous Rep1 and VP1 gene from classical GPV, two chimeric viruses rJN-cVP1 and rJN-cRep1 were generated. Duck infection tests revealed that the non-structural protein Rep1 played a crucial role in the NGPV pathogenicity. The present result lays a solid foundation for further exploring how the Rep protein contributes to the NGPV pathogenesis.
DOI: 10.6084/m9.figshare.21295520.v1
title: <i>Aeromonas salmonicida</i> binds α2-6 linked sialic acid, which is absent among the glycosphingolipid repertoires from skin, gill, stomach, pyloric caecum, and intestine

description: Carbohydrates can both protect against infection and act as targets promoting infection. Mucins are major components of the slimy mucus layer covering the fish epithelia. Mucins can act as decoys for intimate pathogen interaction with the host afforded by binding to glycosphingolipids in the host cell membrane. We isolated and characterized glycosphingolipids from Atlantic salmon skin, gill, stomach, pyloric caeca, and intestine. We characterized the glycosphingolipids using liquid chromatography – mass spectrometry and tandem mass spectrometry and the glycan repertoire was compared with the glycan repertoire of mucins from the same epithelia. We also investigated <i>Aeromonas salmonicida</i> binding using chromatogram and microtiter well based binding assays. We identified 29 glycosphingolipids. All detected acid glycans were of the ganglio-series (unless shorter) and showed a high degree of polysialylation. The non-acid glycans were mostly composed of the neolacto, globo, and ganglio core structures. The glycosphingolipid repertoire differed between epithelia and the proportion of the terminal moieties of the glycosphingolipids did not reflect the terminal moieties on the mucins from the same epithelia. <i>A. salmonicida</i> did not bind the Atlantic salmon glycosphingolipids. Instead, we identified that <i>A. salmonicida</i> binding to sialic acid occurred to α2–6 Neu5Ac but not to α2–3 Neu5Ac. α2–6 Neu5Ac was present on mucins whereas mainly α2–3 Neu5Ac was found on the glycosphingolipids, explaining the difference in <i>A. salmonicida</i> binding ability between these host glycoconjugates. <i>A. salmonicida´s</i> ability to bind to Atlantic salmon mucins, but not the glycosphingolipids, is likely part of the host defence against this pathogen.
DOI: 10.6084/m9.figshare.21600485
title: Screening for eukaryotic motifs in <i>Legionella pneumophila</i> reveals Smh1 as bacterial deacetylase of host histones

description: <i>Legionella pneumophila</i> (<i>L.p</i>.) is a bacterial pathogen which is a common causative agent of pneumonia. In humans, it infects alveolar macrophages and transfers hundreds of virulence factors that interfere with cellular signalling pathways and the transcriptomic landscape to sustain its own replication. By this interaction, it has acquired eukaryote-like protein motifs by gene transfer events that partake in the pathogenicity of <i>Legionella</i>. In a computational screening approach for eukaryotic motifs in the transcriptome of <i>Legionella</i>, we identified the <i>L.p</i>. strain Corby protein ABQ55614 as putative histone-deacetylase and named it “suppressing modifier of histones 1” (Smh1). During infection, Smh1 is translocated from the <i>Legionella</i> vacuole into the host cytosol. When expressed in human macrophage THP-1 cells, Smh1 was localized predominantly in the nucleus, leading to broad histone H3 and H4 deacetylation, blunted expression of a large number of genes (<i>e.g</i>. IL-1β and IL-8), and fostered intracellular bacterial replication. <i>L.p</i>. with a Smh1 knockdown grew normally in media but showed a slight growth defect inside the host cell. Furthermore, Smh1 showed a very potent histone deacetylation activity <i>in vitro</i>, <i>e.g</i>. at H3K14, that could be inhibited by targeted mutation of the putative catalytic center inferred by analogy with eukaryotic HDAC8, and with the deacetylase inhibitor trichostatin A. In summary, Smh1 displays functional homology with class I/II type HDACs. We identified Smh1 as a new <i>Legionella</i> virulence factor with a eukaryote-like histone-deacetylase activity that moderates host gene expression and might pave the way for further histone modifications. IMPORTANCE <i>Legionella pneumophila (L.p.)</i> is a prominent bacterial pathogen, which is a common causative agent of pneumonia. In order to survive inside the host cell, the human macrophage, it profoundly interacts with host cell processes to advance its own replication. In this study, we identify a bacterial factor, Smh1, with yet unknown function as a host histone deacetylase. The activity of this factor in the host cell leads to attenuated gene expression and increased intracellular bacterial replication.