cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.27174534
title: Integrin αVβ3 mediates porcine deltacoronavirus infection and inflammatory response through activation of the FAK-PI3K-AKT-nf-κB signalling pathway

description: Porcine deltacoronavirus (PDCoV) is an emerging porcine enteropathogenic coronavirus that causes acute watery diarrhoea in piglets, resulting in significant economic losses to the global swine industry. However, the underlying mechanism of PDCoV infection is not well defined, which seriously hinders the development of effective drugs and vaccines. Integrins (ITG) are heterodimeric transmembrane glycoproteins that play important roles in the life cycle of many viruses. In the current study, the viral entry pathways of PDCoV were explored and the role of ITGαVβ3 was investigated during PDCoV infection. Our results showed that the lysosomal acidification inhibitor bafilomycin-A1 (Baf-A1) significantly reduced PDCoV infection, while exogenous protease facilitated PDCoV infection and even allowed PDCoV entry to bypass the endosomal pathway, suggesting PDCoV entry into cells via the endocytic pathway and the exogenous protease-mediated pathway simultaneously. Furthermore, ITGαVβ3 was identified to be involved in PDCoV infection, especially during viral entry stages. PDCoV infection triggers the activation of the focal adhesion kinase (FAK)-phosphatidylinositol 3-kinase (PI3K)-serine/threonine-specific protein kinase (AKT) signalling pathway, and this activation is ITGαVβ3-dependent, suggesting that the activation of the FAK-PI3K-AKT signalling pathway during PDCoV infection is mediated by ITGαVβ3. Our results further demonstrated that PDCoV infection induced the expression of inflammatory cytokines, which was mediated by activation of the ITGαVβ3-FAK-PI3K-AKT-nuclear transcription factor-κB (NF-κB) signalling pathway. Overall, the results revealed that ITGαVβ3 is an essential host factor for PDCoV infection and can serve as a supplementary receptor to facilitate PDCoV infection, which can help us to explore the molecular mechanism of PDCoV infection. Identifying the host factors required for entry will be helpful in uncovering the pathogenesis mechanisms and developing antivirals against the emerging coronavirus porcine deltacoronavirus (PDCoV). Herein, we revealed that PDCoV enters cells via the endocytic and exogenous protease-mediated pathways simultaneously. Integrins (ITG) αVβ3 is a host factor required for PDCoV infection, especially during virus adhesion, invasion, and release. Most importantly, PDCoV promotes viral infection by activating the ITGαVβ3-focal adhesion kinase (FAK)-phosphatidylinositol 3-kinase (PI3K)-serine/threonine-specific protein kinase (AKT) signalling pathway and induces inflammation by activating the ITGαVβ3-FAK-PI3K-AKT-NF-κB signalling pathway. Overall, this is the first study to identify ITGαVβ3 as an essential factor for PDCoV infection, which can help us to confirm the molecular regulatory mechanism and provide a comprehensive resource for PDCoV infection.
DOI: 10.6084/m9.figshare.27174534.v1
title: Integrin αVβ3 mediates porcine deltacoronavirus infection and inflammatory response through activation of the FAK-PI3K-AKT-nf-κB signalling pathway

description: Porcine deltacoronavirus (PDCoV) is an emerging porcine enteropathogenic coronavirus that causes acute watery diarrhoea in piglets, resulting in significant economic losses to the global swine industry. However, the underlying mechanism of PDCoV infection is not well defined, which seriously hinders the development of effective drugs and vaccines. Integrins (ITG) are heterodimeric transmembrane glycoproteins that play important roles in the life cycle of many viruses. In the current study, the viral entry pathways of PDCoV were explored and the role of ITGαVβ3 was investigated during PDCoV infection. Our results showed that the lysosomal acidification inhibitor bafilomycin-A1 (Baf-A1) significantly reduced PDCoV infection, while exogenous protease facilitated PDCoV infection and even allowed PDCoV entry to bypass the endosomal pathway, suggesting PDCoV entry into cells via the endocytic pathway and the exogenous protease-mediated pathway simultaneously. Furthermore, ITGαVβ3 was identified to be involved in PDCoV infection, especially during viral entry stages. PDCoV infection triggers the activation of the focal adhesion kinase (FAK)-phosphatidylinositol 3-kinase (PI3K)-serine/threonine-specific protein kinase (AKT) signalling pathway, and this activation is ITGαVβ3-dependent, suggesting that the activation of the FAK-PI3K-AKT signalling pathway during PDCoV infection is mediated by ITGαVβ3. Our results further demonstrated that PDCoV infection induced the expression of inflammatory cytokines, which was mediated by activation of the ITGαVβ3-FAK-PI3K-AKT-nuclear transcription factor-κB (NF-κB) signalling pathway. Overall, the results revealed that ITGαVβ3 is an essential host factor for PDCoV infection and can serve as a supplementary receptor to facilitate PDCoV infection, which can help us to explore the molecular mechanism of PDCoV infection. Identifying the host factors required for entry will be helpful in uncovering the pathogenesis mechanisms and developing antivirals against the emerging coronavirus porcine deltacoronavirus (PDCoV). Herein, we revealed that PDCoV enters cells via the endocytic and exogenous protease-mediated pathways simultaneously. Integrins (ITG) αVβ3 is a host factor required for PDCoV infection, especially during virus adhesion, invasion, and release. Most importantly, PDCoV promotes viral infection by activating the ITGαVβ3-focal adhesion kinase (FAK)-phosphatidylinositol 3-kinase (PI3K)-serine/threonine-specific protein kinase (AKT) signalling pathway and induces inflammation by activating the ITGαVβ3-FAK-PI3K-AKT-NF-κB signalling pathway. Overall, this is the first study to identify ITGαVβ3 as an essential factor for PDCoV infection, which can help us to confirm the molecular regulatory mechanism and provide a comprehensive resource for PDCoV infection.
DOI: 10.6084/m9.figshare.25040361.v1
title: HylS’, a fragment of truncated hyaluronidase of <i>streptococcus suis</i>, contributes to immune evasion by interaction with host complement factor C3b

description: Pathogenic bacteria have evolved many strategies to evade surveillance and attack by complements. <i>Streptococcus suis</i> is an important zoonotic pathogen that infects humans and pigs. Hyaluronidase (HylA) has been reported to be a potential virulence factor of <i>S. suis</i>. However, in this study, it was discovered that the genomic region encoding HylA of the virulent <i>S. suis</i> strain SC19 and other ST1 strains was truncated into four fragments when aligned with a strain containing intact HylA and possessing hyaluronidase activity. As a result, SC19 had no hyaluronidase activity, but one truncated HylA fragment, designated as HylS,’ directly interacted with complement C3b, as confirmed by western ligand blotting, pull-down, and ELISA assays. The deposition of C3b and membrane attack complex (MAC) formation on the surface of a HylS’-deleted mutant (Δ<i>hylS’</i>) was significantly increased compared to wild-type SC19. In human sera and whole blood, Δ<i>hylS’</i> survival was significantly reduced compared to that in SC19. The resistance of Δ<i>hylS’</i> to macrophages and human polymorphonuclear neutrophil PMNs also decreased. In a mouse infection model, Δ<i>hylS’</i> showed reduced lethality and lower bacterial load in the organs compared to that of SC19. We conclude that the truncated hyaluronidase HylS’ fragment contributes to complement evasion and the pathogenesis of <i>S. suis</i>.
DOI: 10.6084/m9.figshare.25459373
title: Alpha1-antitrypsin impacts innate host–pathogen interactions with <i>Candida albicans</i> by stimulating fungal filamentation

description: Our immune system possesses sophisticated mechanisms to cope with invading microorganisms, while pathogens evolve strategies to deal with threats imposed by host immunity. Human plasma protein α1-antitrypsin (AAT) exhibits pleiotropic immune-modulating properties by both preventing immunopathology and improving antimicrobial host defence. Genetic associations suggested a role for AAT in candidemia, the most frequent fungal blood stream infection in intensive care units, yet little is known about how AAT influences interactions between <i>Candida albicans</i> and the immune system. Here, we show that AAT differentially impacts fungal killing by innate phagocytes. We observed that AAT induces fungal transcriptional reprogramming, associated with cell wall remodelling and downregulation of filamentation repressors. At low concentrations, the cell-wall remodelling induced by AAT increased immunogenic β-glucan exposure and consequently improved fungal clearance by monocytes. Contrastingly, higher AAT concentrations led to excessive <i>C. albicans</i> filamentation and thus promoted fungal immune escape from monocytes and macrophages. This underscores that fungal adaptations to the host protein AAT can differentially define the outcome of encounters with innate immune cells, either contributing to improved immune recognition or fungal immune escape.
DOI: 10.6084/m9.figshare.25459373.v2
title: Alpha1-antitrypsin impacts innate host–pathogen interactions with <i>Candida albicans</i> by stimulating fungal filamentation

description: Our immune system possesses sophisticated mechanisms to cope with invading microorganisms, while pathogens evolve strategies to deal with threats imposed by host immunity. Human plasma protein α1-antitrypsin (AAT) exhibits pleiotropic immune-modulating properties by both preventing immunopathology and improving antimicrobial host defence. Genetic associations suggested a role for AAT in candidemia, the most frequent fungal blood stream infection in intensive care units, yet little is known about how AAT influences interactions between <i>Candida albicans</i> and the immune system. Here, we show that AAT differentially impacts fungal killing by innate phagocytes. We observed that AAT induces fungal transcriptional reprogramming, associated with cell wall remodelling and downregulation of filamentation repressors. At low concentrations, the cell-wall remodelling induced by AAT increased immunogenic β-glucan exposure and consequently improved fungal clearance by monocytes. Contrastingly, higher AAT concentrations led to excessive <i>C. albicans</i> filamentation and thus promoted fungal immune escape from monocytes and macrophages. This underscores that fungal adaptations to the host protein AAT can differentially define the outcome of encounters with innate immune cells, either contributing to improved immune recognition or fungal immune escape.
DOI: 10.6084/m9.figshare.24580575
title: The twin-arginine translocation system is vital for cell adhesion and uptake of iron in the cystic fibrosis pathogen <i>Achromobacter xylosoxidans</i>

description: <i>Achromobacter xylosoxidans</i> is an emerging pathogen that causes airway infections in patients with cystic fibrosis. Knowledge of virulence factors and protein secretion systems in this bacterium is limited. Twin arginine translocation (Tat) is a protein secretion system that transports folded proteins across the inner cell membranes of gram-negative bacteria. Tat has been shown to be important for virulence and cellular processes in many different bacterial species. This study aimed to investigate the role of Tat in iron metabolism and host cell adhesion in <i>A. xylosoxidans</i>. Putative Tat substrates in <i>A.</i> <i>xylosoxidans</i> were identified using the TatFind, TatP, and PRED-Tat prediction tools. An isogenic <i>tatC</i> deletion mutant (ΔtatC) was generated and phenotypically characterized. The wild-type and ΔtatC <i>A.</i> <i>xylosoxidans</i> were fractionated into cytosolic, membrane, and periplasmic fractions, and the expressed proteome of the different fractions was analysed using liquid chromatography-mass spectrometry (LC-MS/MS). A total of 128 putative Tat substrates were identified in the <i>A.</i> <i>xylosoxidans</i> proteome. The ΔtatC mutant showed attenuated host cell adhesion, growth rate, and iron acquisition. Twenty predicted Tat substrates were identified as expressed proteins in the periplasmic compartment, nine of which were associated with the wild type. The data indicate that Tat secretion is important for iron acquisition and host cell adhesion in <i>A.</i> <i>xylosoxidans</i>.
DOI: 10.6084/m9.figshare.24580575.v1
title: The twin-arginine translocation system is vital for cell adhesion and uptake of iron in the cystic fibrosis pathogen <i>Achromobacter xylosoxidans</i>

description: <i>Achromobacter xylosoxidans</i> is an emerging pathogen that causes airway infections in patients with cystic fibrosis. Knowledge of virulence factors and protein secretion systems in this bacterium is limited. Twin arginine translocation (Tat) is a protein secretion system that transports folded proteins across the inner cell membranes of gram-negative bacteria. Tat has been shown to be important for virulence and cellular processes in many different bacterial species. This study aimed to investigate the role of Tat in iron metabolism and host cell adhesion in <i>A. xylosoxidans</i>. Putative Tat substrates in <i>A.</i> <i>xylosoxidans</i> were identified using the TatFind, TatP, and PRED-Tat prediction tools. An isogenic <i>tatC</i> deletion mutant (ΔtatC) was generated and phenotypically characterized. The wild-type and ΔtatC <i>A.</i> <i>xylosoxidans</i> were fractionated into cytosolic, membrane, and periplasmic fractions, and the expressed proteome of the different fractions was analysed using liquid chromatography-mass spectrometry (LC-MS/MS). A total of 128 putative Tat substrates were identified in the <i>A.</i> <i>xylosoxidans</i> proteome. The ΔtatC mutant showed attenuated host cell adhesion, growth rate, and iron acquisition. Twenty predicted Tat substrates were identified as expressed proteins in the periplasmic compartment, nine of which were associated with the wild type. The data indicate that Tat secretion is important for iron acquisition and host cell adhesion in <i>A.</i> <i>xylosoxidans</i>.
DOI: 10.6084/m9.figshare.25459373.v1
title: Alpha1-antitrypsin impacts innate host-pathogen interactions with <i>Candida albicans</i> by stimulating fungal filamentation

description: Our immune system possesses sophisticatedmechanisms to cope with invading microorganisms, while pathogensevolve strategies to deal with threats imposed by host immunity. Thehuman plasma protein α1-antitrypsin (AAT) exhibits pleiotropicimmune-modulating properties by both preventing immunopathology andimproving antimicrobial host defence. Genetic associations suggesteda role for AAT in candidemia, the most frequent fungal bloodstreaminfection in the ICU, yet little is known about how AAT influencesinteractions between <i>Candidaalbicans</i> and the immunesystem. Here we show that AAT differentiallyimpacts fungal killing by innate phagocytes. We observed that AATinduces fungal transcriptional reprogramming, associated with cellwall remodelling and downregulation of filamentation repressors. Atlow concentrations, the cell-wall remodelling induced by AAT increasedimmunogenic β-glucan exposure and consequently improved fungal clearance by monocytes.Contrastingly, higher AAT concentrations led to excessive <i>C. albicans</i>filamentation and thus promoted fungal immune escape from monocytesand macrophages. This underscores that fungal adaptationsto the host protein AAT can differentially define the outcome ofencounters with innate immune cells, eithercontributing to improved immune recognition or fungal immune escape.
DOI: 10.6084/m9.figshare.27604285
title: Deletion of glycosyltransferase <i>galE</i> impairs the InlB anchoring and pathogenicity of <i>Listeria monocytogenes</i>

description: <i>Listeria monocytogenes</i> (<i>L. monocytogenes</i>) is a foodborne intracellular pathogen that causes serious disease in both humans and animals. InlB is the major internalin protein of <i>L. monocytogenes</i>, which anchors to the bacterial surface and mediates its invasion into various host cells. Recent studies have shown that galactosylation of the cell wall polymer wall teichoic acid (WTA) is essential for InlB anchoring on the cell surface of <i>L. monocytogenes</i> serotype 4b strains. Galactosylation of WTA is exerted by the coordinated action of several glycosyltransferases, including GalU, GalE, GtcA, GttA, and GttB. Among these glycosyltransferases, GttA and GttB are specific to serotype 4b strains, whereas GalE, GalU, and GtcA are conserved across all serotypes. The role of GalE in InlB anchoring and <i>L. monocytogenes</i> pathogenicity remains unclear. In this study, we deleted the <i>galE</i> gene, which is involved in galactosylation, from <i>L. monocytogenes</i> strain ScottA. We found that <i>galE</i> deletion reduced InlB anchoring, weakened bacterial adhesion and invasion of Caco-2 cells (human colorectal adenocarcinoma cells) and MGC803 cells (human gastric carcinoma cells), increased phagocytosis but decreased proliferation in RAW264.7 cells (mouse mononuclear macrophage leukaemia cells), and decreased bacteria load, mortality, and tissue damage in infected mice. Taken together, <i>galE</i> deletion significantly reduced the anchoring of InlB and weakened the pathogenicity of <i>L. monocytogenes</i>. This finding provides new insights into the correlation between cell wall modification and pathogenicity of <i>L. monocytogenes</i>.
DOI: 10.6084/m9.figshare.27604285.v1
title: Deletion of glycosyltransferase <i>galE</i> impairs the InlB anchoring and pathogenicity of <i>Listeria monocytogenes</i>

description: <i>Listeria monocytogenes</i> (<i>L. monocytogenes</i>) is a foodborne intracellular pathogen that causes serious disease in both humans and animals. InlB is the major internalin protein of <i>L. monocytogenes</i>, which anchors to the bacterial surface and mediates its invasion into various host cells. Recent studies have shown that galactosylation of the cell wall polymer wall teichoic acid (WTA) is essential for InlB anchoring on the cell surface of <i>L. monocytogenes</i> serotype 4b strains. Galactosylation of WTA is exerted by the coordinated action of several glycosyltransferases, including GalU, GalE, GtcA, GttA, and GttB. Among these glycosyltransferases, GttA and GttB are specific to serotype 4b strains, whereas GalE, GalU, and GtcA are conserved across all serotypes. The role of GalE in InlB anchoring and <i>L. monocytogenes</i> pathogenicity remains unclear. In this study, we deleted the <i>galE</i> gene, which is involved in galactosylation, from <i>L. monocytogenes</i> strain ScottA. We found that <i>galE</i> deletion reduced InlB anchoring, weakened bacterial adhesion and invasion of Caco-2 cells (human colorectal adenocarcinoma cells) and MGC803 cells (human gastric carcinoma cells), increased phagocytosis but decreased proliferation in RAW264.7 cells (mouse mononuclear macrophage leukaemia cells), and decreased bacteria load, mortality, and tissue damage in infected mice. Taken together, <i>galE</i> deletion significantly reduced the anchoring of InlB and weakened the pathogenicity of <i>L. monocytogenes</i>. This finding provides new insights into the correlation between cell wall modification and pathogenicity of <i>L. monocytogenes</i>.
DOI: 10.6084/m9.figshare.26954706
title: N-acetylcysteine promotes doxycycline resistance in the bacterial pathogen <i>Edwardsiella tarda</i>

description: Bacterial resistance poses a significant threat to both human and animal health. N-acetylcysteine (NAC), which is used as an anti-inflammatory, has been shown to have distinct and contrasting impacts on bacterial resistance. However, the precise mechanism underlying the relationship between NAC and bacterial resistance remains unclear and requires further investigation. In this study, we study the effect of NAC on bacterial resistance and the underlying mechanisms. Specifically, we examine the effects of NAC on <i>Edwardsiella tarda</i> ATCC15947, a pathogen that exhibits resistance to many antibiotics. We find that NAC can promote resistance of <i>E. tarda</i> to many antibiotics, such as doxycycline, resulting in an increase in the bacterial survival rate. Through proteomic analysis, we demonstrate that NAC activates the amino acid metabolism pathway in <i>E. tarda</i>, leading to elevated intracellular glutathione (GSH) levels and reduced reactive oxygen species (ROS). Additionally, NAC reduces antibiotic influx while enhancing efflux, thus maintaining low intracellular antibiotic concentrations. We also propose that NAC promotes protein aggregation, thus contributing to antibiotic resistance. Our study describes the mechanism underlying <i>E. tarda</i> resistance to doxycycline and cautions against the indiscriminate use of metabolite adjuvants.
DOI: 10.6084/m9.figshare.26954706.v2
title: N-acetylcysteine promotes doxycycline resistance in the bacterial pathogen <i>Edwardsiella tarda</i>

description: Bacterial resistance poses a significant threat to both human and animal health. N-acetylcysteine (NAC), which is used as an anti-inflammatory, has been shown to have distinct and contrasting impacts on bacterial resistance. However, the precise mechanism underlying the relationship between NAC and bacterial resistance remains unclear and requires further investigation. In this study, we study the effect of NAC on bacterial resistance and the underlying mechanisms. Specifically, we examine the effects of NAC on <i>Edwardsiella tarda</i> ATCC15947, a pathogen that exhibits resistance to many antibiotics. We find that NAC can promote resistance of <i>E. tarda</i> to many antibiotics, such as doxycycline, resulting in an increase in the bacterial survival rate. Through proteomic analysis, we demonstrate that NAC activates the amino acid metabolism pathway in <i>E. tarda</i>, leading to elevated intracellular glutathione (GSH) levels and reduced reactive oxygen species (ROS). Additionally, NAC reduces antibiotic influx while enhancing efflux, thus maintaining low intracellular antibiotic concentrations. We also propose that NAC promotes protein aggregation, thus contributing to antibiotic resistance. Our study describes the mechanism underlying <i>E. tarda</i> resistance to doxycycline and cautions against the indiscriminate use of metabolite adjuvants.
DOI: 10.6084/m9.figshare.26068078
title: A shared mechanism of multidrug resistance in laboratory-evolved uropathogenic <i>Escherichia coli</i>

description: The emergence of multidrug-resistant bacteria poses a significant threat to human health, necessitating a comprehensive understanding of their underlying mechanisms. Uropathogenic <i>Escherichia coli</i> (UPEC), the primary causative agent of urinary tract infections, is frequently associated with multidrug resistance and recurrent infections. To elucidate the mechanism of resistance of UPEC to beta-lactam antibiotics, we generated ampicillin-resistant UPEC strains through continuous exposure to low and high levels of ampicillin in the laboratory, referred to as Low Amp<sup>R</sup> and High Amp<sup>R</sup>, respectively. Whole-genome sequencing revealed that both Low and High Amp<sup>R</sup> strains contained mutations in the <i>marR</i>, <i>acrR</i>, and <i>envZ</i> genes. The High Amp<sup>R</sup> strain exhibited a single additional mutation in the <i>nlpD</i> gene. Using protein modeling and qRT-PCR analyses, we validated the contributions of each mutation in the identified genes to antibiotic resistance in the Amp<sup>R</sup> strains, including a decrease in membrane permeability, increased expression of multidrug efflux pump, and inhibition of cell lysis. Furthermore, the Amp<sup>R</sup> strain does not decrease the bacterial burden in the mouse bladder even after continuous antibiotic treatment <i>in vivo</i>, implicating the increasing difficulty in treating host infections caused by the Amp<sup>R</sup> strain. Interestingly, ampicillin-induced mutations also result in multidrug resistance in UPEC, suggesting a common mechanism by which bacteria acquire cross-resistance to other classes of antibiotics.