cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.29846758.v2
title: A novel <i>Klebsiella pneumoniae</i> diguanylate cyclase contributes to intestinal cell adhesion, biofilm formation, iron utilization, and <i>in vivo</i> virulence by gastrointestinal infection

description: <i>Klebsiella pneumoniae</i> is responsible for various infections such as bacteremia, urinary tract infections, pneumonia, and liver abscesses. Multidrug-resistant <i>K. pneumoniae</i> infections pose a critical public health threat, often associated with high mortality rates. The emergence of hypervirulent <i>K. pneumoniae</i> has also raised global health concerns due to its invasive disease potential. Clinical studies suggest intestinal colonization by <i>K. pneumoniae</i> as a risk factor for subsequent infections, but the underlying mechanisms remain unclear. Cyclic di-GMP (c-di-GMP), a bacterial signaling molecule synthesized by diguanylate cyclases (DGCs), controls various cellular processes and is absent in higher organisms, making it an attractive target for antimicrobial development. In this study, we identified a novel DGC, designated as DgcG, in <i>K. pneumoniae</i>, which plays a pivotal role in gastrointestinal colonization and pathogenesis. Using genetic deletion and complementation analyses in a bacteremia and liver abscesses-inducing strain Ca0437, we observed that DgcG promoted intestinal adherence, biofilm formation, iron utilization, and <i>in vivo</i> virulence. RT-qPCR showed that DgcG regulated genes involved in type 3 fimbrial expression and iron transport. In a gastrointestinal infection model of female BALB/cByl mice, <i>dgcG</i> deletion significantly reduced host mortality and bacterial load in the liver, spleen, and intestines, underscoring its role in enhancing bacterial survival and dissemination. Additionally, <i>dgcG</i> gene was found highly conserved and prevalent among diverse <i>K. pneumoniae</i> isolates. These findings provide new insights into c-di-GMP-mediated virulence regulation in <i>K. pneumoniae</i> and highlight DgcG as a potential therapeutic target for controlling <i>K. pneumoniae</i> infections, especially amidst the growing global antimicrobial resistance crisis.
DOI: 10.6084/m9.figshare.30607395.v1
title: ROS-induced allosteric modulation of NikR promotes <i>helicobacter pylori</i> biofilm formation by attenuating FlgR-dependent inhibition of the molybdate transport system

description: <i>Helicobacter pylori</i> biofilm formation is crucial for its persistence and transmission, constituting a notable public health concern. Understanding the regulatory mechanisms driving biofilm initiation is vital for developing effective control strategies. This study reveals a previously uncharacterized regulatory mechanism where reactive oxygen species (ROS) promote <i>H. pylori</i> biofilm formation by modulating the key flagellar regulator FlgR and the molybdate transport system ModABD. We demonstrate that FlgR acts as a repressor of biofilm development. Mechanistically, FlgR inhibits the transcription of the <i>modABD</i> operon, essential for biofilm formation, by suppressing the activity of sigma factor σ<sup>28</sup>. Crucially, we identify the nickel-responsive regulator NikR as a repressor of <i>flgR</i> expression. ROS induce a conformational change in NikR, converting it to its DNA-binding holo-form, which directly binds the <i>flgR</i> promoter and represses its expression. This repression alleviates FlgR-mediated inhibition of σ<sup>28</sup>, thereby de-repressing the <i>modABD</i> operon and facilitating the transition from planktonic to biofilm growth. Our findings uncover a previously unknown ROS-NikR-FlgR-σ<sup>28</sup>-ModABD signaling axis governing <i>H. pylori</i> biofilm formation.
DOI: 10.6084/m9.figshare.29846758.v1
title: A novel <i>klebsiella pneumoniae</i> diguanylate cyclase contributes to intestinal cell adhesion, biofilm formation, iron utilization, and <i>in vivo</i> virulence by gastrointestinal infection

description: <i>Klebsiella pneumoniae</i> is responsible for various infections such as bacteraemia, urinary tract infections, pneumonia, and liver abscesses. Multidrug-resistant <i>K. pneumoniae</i> infections pose a critical public health threat, often associated with high mortality rates. The emergence of hypervirulent <i>K. pneumoniae</i> has also raised global health concerns due to its invasive disease potential. Clinical studies suggest intestinal colonization by <i>K. pneumoniae</i> as a risk factor for subsequent infections but underlying mechanisms remain unclear. Cyclic di-GMP (c-di-GMP), a bacterial signalling molecule synthesized by diguanylate cyclases (DGCs), controls various cellular processes and is absent in higher organisms, making it an attractive target for antimicrobial development. In this study, we identified a novel DGC, designated as DgcG, in <i>K. pneumoniae</i>, which plays a pivotal role in gastrointestinal colonization and pathogenesis. Using genetic deletion and complementation analyses in a bacteraemia and liver abscesses-inducing strain Ca0437, we observed that DgcG promoted intestinal adherence, biofilm formation, iron utilization, and <i>in vivo</i> virulence. RT-qPCR showed that DgcG regulated genes involved in type 3 fimbrial expression and iron transport. In a gastrointestinal infection model of female BALB/cByl mice, <i>dgcG</i> deletion significantly reduced host mortality and bacterial load in the liver, spleen, and intestines, underscoring its role in enhancing bacterial survival and dissemination. Additionally, <i>dgcG</i> gene was found highly conserved and prevalent among diverse <i>K. pneumoniae</i> isolates. These findings provide new insights into c-di-GMP-mediated virulence regulation in <i>K. pneumoniae</i> and highlight DgcG as a potential therapeutic target for controlling <i>K. pneumoniae</i> infections, especially amidst the growing global antimicrobial resistance crisis.
DOI: 10.6084/m9.figshare.29436559
title: <i>Edwardsiella piscicida</i> employs C3 derivative to mediate internalization and infection via the teleost-specific receptor

description: <i>Edwardsiella piscicida</i> is a prominent fish pathogen, and spreads the infection to humans and mammals. It can resist serum killing and invade the host phagocytic cells. However, the precise mechanisms underlying <i>E. piscicida</i> infection remain unclear. In this study, we found that <i>E. piscicida</i> could bind to complement factor H and recruit complement factor I from <i>Paralichthys olivaceus</i> (Po) serum, leading to the degradation of complement recognition molecule PoC3b to PoC3dg on the bacterial surface. <i>E. piscicida</i> also bound to peripheral blood leukocytes, depending on the teleost-specific interaction between PoC3dg and the integrin beta VWA (INB) domain of PoCD18, whereby facilitating bacterial internalization and infection. When PoCD18 was knocked down or blocked, bacterial infection and tissue lesions were significantly decreased. Mechanistically, the intracellular domain of PoCD18 subsequently interacted with PoCytohesin and triggered the phosphorylation of the phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (Akt) signalling pathway. Furthermore, inhibition of the PI3K/Akt pathway impaired the internalization and pathogenicity of <i>E. piscicida</i>. Overall, we demonstrated for the first time that <i>E. piscicida</i> utilized the C3dg-CD18 axis to facilitate internalization, thereby targeting immune evasion and promoting systemic infections. These results provide new insights into the pathogen–host interaction mechanism and a potential target to control edwardsiellosis.
DOI: 10.6084/m9.figshare.29436559.v1
title: <i>Edwardsiella piscicida</i> employs C3 derivative to mediate internalization and infection via the teleost-specific receptor

description: <i>Edwardsiella piscicida</i> is a prominent fish pathogen, and spreads the infection to humans and mammals. It can resist serum killing and invade the host phagocytic cells. However, the precise mechanisms underlying <i>E. piscicida</i> infection remain unclear. In this study, we found that <i>E. piscicida</i> could bind to complement factor H and recruit complement factor I from <i>Paralichthys olivaceus</i> (Po) serum, leading to the degradation of complement recognition molecule PoC3b to PoC3dg on the bacterial surface. <i>E. piscicida</i> also bound to peripheral blood leukocytes, depending on the teleost-specific interaction between PoC3dg and the integrin beta VWA (INB) domain of PoCD18, whereby facilitating bacterial internalization and infection. When PoCD18 was knocked down or blocked, bacterial infection and tissue lesions were significantly decreased. Mechanistically, the intracellular domain of PoCD18 subsequently interacted with PoCytohesin and triggered the phosphorylation of the phosphatidylinositol 3-kinase (PI3K)/serine-threonine protein kinase (Akt) signalling pathway. Furthermore, inhibition of the PI3K/Akt pathway impaired the internalization and pathogenicity of <i>E. piscicida</i>. Overall, we demonstrated for the first time that <i>E. piscicida</i> utilized the C3dg-CD18 axis to facilitate internalization, thereby targeting immune evasion and promoting systemic infections. These results provide new insights into the pathogen–host interaction mechanism and a potential target to control edwardsiellosis.
DOI: 10.6084/m9.figshare.29856121
title: The CueR-regulated transporters CopA and CusFABC coordinate copper detoxification in <i>Vibrio parahaemolyticus</i>

description: <i>Vibrio parahaemolyticus</i> is a zoonotic pathogen that poses a serious threat to shrimp aquaculture and public health worldwide. Copper (Cu) serves as a catalytic cofactor and structural element in bacteria but is toxic in excess. Herein, we report that the CueR-regulated transporters CopA and CusFABC coordinate Cu detoxification in <i>V. parahaemolyticus</i>. Through RNA sequencing, we show that most genes in the CueR and Fur regulons are significantly upregulated during <i>V. parahaemolyticus</i> response to external Cu. Quantitative real-time PCR (qRT-PCR) showed that <i>copA</i> and <i>cusA</i> are strongly induced by Cu. Growth curve analyses and spot dilution assay revealed that CopA and CusFABC protect <i>V. parahaemolyticus</i> against Cu-induced bactericidal effects. Inductively coupled plasma-mass spectrometry revealed that CopA and CusFABC are involved in maintaining Cu and Fe homoeostasis. Additionally, CopA promotes <i>V. parahaemolyticus</i> resistance to pyrithione. In a competitive-infection assay, the <i>copA</i> and <i>cusFABC</i> double mutant, but not the single mutants, was significantly attenuated in colonization of the zebrafish intestine. Lastly, qRT-PCR, RNA sequencing, β-galactosidase activity, and AIDmut-Seq analyses revealed that CueR can bind to the promoters of <i>copA</i> and <i>cusFABC</i>, and positively regulate their expression. Collectively, <i>V. parahaemolyticus</i> utilizes the CueR-regulated transporters CopA and CusFABC to coordinate Cu detoxification and colonization of the zebrafish intestine.
DOI: 10.6084/m9.figshare.29856121.v1
title: The CueR-regulated transporters CopA and CusFABC coordinate copper detoxification in <i>Vibrio parahaemolyticus</i>

description: <i>Vibrio parahaemolyticus</i> is a zoonotic pathogen that poses a serious threat to shrimp aquaculture and public health worldwide. Copper (Cu) serves as a catalytic cofactor and structural element in bacteria but is toxic in excess. Herein, we report that the CueR-regulated transporters CopA and CusFABC coordinate Cu detoxification in <i>V. parahaemolyticus</i>. Through RNA sequencing, we show that most genes in the CueR and Fur regulons are significantly upregulated during <i>V. parahaemolyticus</i> response to external Cu. Quantitative real-time PCR (qRT-PCR) showed that <i>copA</i> and <i>cusA</i> are strongly induced by Cu. Growth curve analyses and spot dilution assay revealed that CopA and CusFABC protect <i>V. parahaemolyticus</i> against Cu-induced bactericidal effects. Inductively coupled plasma-mass spectrometry revealed that CopA and CusFABC are involved in maintaining Cu and Fe homoeostasis. Additionally, CopA promotes <i>V. parahaemolyticus</i> resistance to pyrithione. In a competitive-infection assay, the <i>copA</i> and <i>cusFABC</i> double mutant, but not the single mutants, was significantly attenuated in colonization of the zebrafish intestine. Lastly, qRT-PCR, RNA sequencing, β-galactosidase activity, and AIDmut-Seq analyses revealed that CueR can bind to the promoters of <i>copA</i> and <i>cusFABC</i>, and positively regulate their expression. Collectively, <i>V. parahaemolyticus</i> utilizes the CueR-regulated transporters CopA and CusFABC to coordinate Cu detoxification and colonization of the zebrafish intestine.
DOI: 10.6084/m9.figshare.29901313
title: High-risk clonal groups of avian pathogenic <i>Escherichia coli</i> (APEC) demonstrate heterogeneous phenotypic characteristics <i>in vitro</i> and <i>in vivo</i>

description: Avian Pathogenic <i>Escherichia coli</i> (APEC), a major bacterial pathogen of poultry, comprises a diverse range of high-risk clonal groups. However how these lineages interact with avian host cells remains poorly characterized. This study examined the ability of key APEC clonal groups to adhere to, invade, and survive within avian host cells, alongside assessing their virulence in the <i>Galleria mellonella</i> infection model. Genomic analysis of APEC from a UK turkey colibacillosis outbreak identified ST-101 as the dominant clonal group, carrying numerous virulence factors. ST-101 was compared to other high-risk APEC clonal groups (ST-23, ST-140, ST-95, ST-117). Utilizing <i>in vitro</i> cell culture models, APEC isolates displayed comparable adhesion to 8E11 chicken epithelial gut and HD11 chicken macrophage cell lines. APEC ST-95, ST-101, and ST-140 demonstrated increased invasion of 8E11 cells, and intracellular survival within HD11 macrophages, relative to ST-23 and ST-117, suggesting pronounced phenotypic differences between clonal groups. However, in HD11 cell assays, no difference in magnitude of elicited immune response was observed between lineages, indicating differing intracellular survival was not a result of immune response modulation. <i>In vivo</i> virulence in the <i>Galleria mellonella</i> infection model was also observed to differ between APEC genotypes, with ST-117 inducing the highest mortality, despite the comparatively lower epithelial invasion and intramacrophage survival for other lineages. Collectively, this suggests that diverse APEC genotypes have distinct phenotypic profiles <i>in vitro</i> and <i>in vivo</i>. These results highlight the need for intervention strategies that can simultaneously target a broad range of pathogenic lineages.
DOI: 10.6084/m9.figshare.29901313.v1
title: High-risk clonal groups of avian pathogenic <i>Escherichia coli</i> (APEC) demonstrate heterogeneous phenotypic characteristics <i>in vitro</i> and <i>in vivo</i>

description: Avian Pathogenic <i>Escherichia coli</i> (APEC), a major bacterial pathogen of poultry, comprises a diverse range of high-risk clonal groups. However how these lineages interact with avian host cells remains poorly characterized. This study examined the ability of key APEC clonal groups to adhere to, invade, and survive within avian host cells, alongside assessing their virulence in the <i>Galleria mellonella</i> infection model. Genomic analysis of APEC from a UK turkey colibacillosis outbreak identified ST-101 as the dominant clonal group, carrying numerous virulence factors. ST-101 was compared to other high-risk APEC clonal groups (ST-23, ST-140, ST-95, ST-117). Utilizing <i>in vitro</i> cell culture models, APEC isolates displayed comparable adhesion to 8E11 chicken epithelial gut and HD11 chicken macrophage cell lines. APEC ST-95, ST-101, and ST-140 demonstrated increased invasion of 8E11 cells, and intracellular survival within HD11 macrophages, relative to ST-23 and ST-117, suggesting pronounced phenotypic differences between clonal groups. However, in HD11 cell assays, no difference in magnitude of elicited immune response was observed between lineages, indicating differing intracellular survival was not a result of immune response modulation. <i>In vivo</i> virulence in the <i>Galleria mellonella</i> infection model was also observed to differ between APEC genotypes, with ST-117 inducing the highest mortality, despite the comparatively lower epithelial invasion and intramacrophage survival for other lineages. Collectively, this suggests that diverse APEC genotypes have distinct phenotypic profiles <i>in vitro</i> and <i>in vivo</i>. These results highlight the need for intervention strategies that can simultaneously target a broad range of pathogenic lineages.
DOI: 10.6084/m9.figshare.29924097
title: Intratumorally specific microbial-derived lipopolysaccharide contributes to non-small cell lung cancer progression

description: As an emerging component of the tumor microenvironment (TME), the intratumoural microbiota imperceptibly influences the progression of various human malignancies. However, the critical intratumoural microbiota and its role in non-small cell lung cancer (NSCLC) progression have not been fully elucidated. Here, we used high-throughput sequencing and clinical samples analysis to identify the relationship between intratumoural bacteria and NSCLC progression. The results showed that significant abnormalities in the intratumoural microbiota of NSCLC. Specifically, the relative abundance of gram-negative bacteria in tumor was significantly increased, and network analysis revealed that <i>Escherichia-Shigella</i> and <i>unclassified_f__Enterobacteriaceae</i>, which have strong abilities to synthesize the bacterial toxin LPS, significantly promoted tumor proliferation. Mechanistically, we found that <i>Escherichia-Shigella-</i> and <i>unclassified_f__Enterobacteriaceae</i>-derived LPS activated the TLR4-mTOR-NF-κB-IL-6 axis to facilitate NSCLC cell proliferation, whereas rapamycin effectively delayed LPS-induced tumor cell proliferation in vitro and in vivo functional experiments. Receiver operating characteristic curves revealed that the combination of intratumoural bacterial concentration, <i>Escherichia-Shigella</i> abundance, <i>unclassified_f__Enterobacteriaceae</i> abundance, and LPS content had greater diagnostic validity in predicting the probability of NSCLC, and the detection of these factors in blood has potential for using the non-invasive diagnosis of NSCLC. Overall, this study revealed the mechanism by which LPS from specific bacteria in TME promoted tumor development, providing new strategies for NSCLC treatment and diagnosis from a microbial perspective.
DOI: 10.6084/m9.figshare.29924097.v1
title: Intratumorally specific microbial-derived lipopolysaccharide contributes to non-small cell lung cancer progression

description: As an emerging component of the tumor microenvironment (TME), the intratumoural microbiota imperceptibly influences the progression of various human malignancies. However, the critical intratumoural microbiota and its role in non-small cell lung cancer (NSCLC) progression have not been fully elucidated. Here, we used high-throughput sequencing and clinical samples analysis to identify the relationship between intratumoural bacteria and NSCLC progression. The results showed that significant abnormalities in the intratumoural microbiota of NSCLC. Specifically, the relative abundance of gram-negative bacteria in tumor was significantly increased, and network analysis revealed that <i>Escherichia-Shigella</i> and <i>unclassified_f__Enterobacteriaceae</i>, which have strong abilities to synthesize the bacterial toxin LPS, significantly promoted tumor proliferation. Mechanistically, we found that <i>Escherichia-Shigella-</i> and <i>unclassified_f__Enterobacteriaceae</i>-derived LPS activated the TLR4-mTOR-NF-κB-IL-6 axis to facilitate NSCLC cell proliferation, whereas rapamycin effectively delayed LPS-induced tumor cell proliferation in vitro and in vivo functional experiments. Receiver operating characteristic curves revealed that the combination of intratumoural bacterial concentration, <i>Escherichia-Shigella</i> abundance, <i>unclassified_f__Enterobacteriaceae</i> abundance, and LPS content had greater diagnostic validity in predicting the probability of NSCLC, and the detection of these factors in blood has potential for using the non-invasive diagnosis of NSCLC. Overall, this study revealed the mechanism by which LPS from specific bacteria in TME promoted tumor development, providing new strategies for NSCLC treatment and diagnosis from a microbial perspective.
DOI: 10.6084/m9.figshare.30231153
title: Pathological protection and molecular regulation of cystatin B in Nile tilapia (<i>Oreochromis niloticus</i>) bacterial disease

description: Cystatin B (CSTB) is an endogenous cysteine protease inhibitor that plays a critical role in the modulation of numerous biological processes, involving immune responses, apoptosis, and inflammation in mammals. However, its immunological functions in teleost, particularly Nile tilapia (<i>Oreochromis niloticus</i>) remain unclear. In the present study, the <i>CSTB</i> was cloned and characterized from Nile tilapia (<i>On-CSTB</i>) and its role in bacterial infection was revealed. The On-CSTB open reading frame is 300 bp encoding 99 amino acids that contains a conserved cystatin domain. Multiple sequence alignment analysis revealed that On-CSTB share over 75% identity with fish lineages, and 45% identity with mammals. qPCR analysis showed that <i>On-CSTB</i> is widely expressed across various tissues and highly expressed in blood cells and intestines and can be significantly inducted by <i>Streptococcus agalactiae</i> (<i>S. agalactiae</i>) and <i>Aeromonas hydrophila</i> (<i>A. hydrophila</i>). In vivo experiments demonstrated that On-CSTB protein could suppress inflammation while participating in the MyD88/NF-κB signaling pathway and inflammasome activation, affecting apoptosis and pyroptosis processes. Moreover, On-CSTB contributed to enhanced tissue integrity and alleviated pathological damage. These findings collectively highlight On-CSTB as a crucial immunomodulator that contributes to host defense and tissue protection in fish. The present study offers novel perspectives on the immunomodulatory role of CSTB in tilapia, providing a basis for disease resistance strategies in aquaculture.