cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.30577009.v2
title: Targeting methicillin-resistant <i>Staphylococcus aureus</i>: The comprehensive action of ent-kaurane diterpenoids on bacterial integrity

description: Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) represents a considerable challenge to global health owing to its resistance to antibiotics. In our prior research, we identified four ent-kaurane diterpenoids (compounds <b>1–4</b>) isolated from <i>Siegesbeckia orientalis</i> L., which exhibited anti-MRSA activity. Nevertheless, the precise mechanisms by which these compounds exert their effects remain to be fully elucidated. This study aims to comprehensively evaluate the anti-MRSA properties and explore the biological processes associated with the activity of compounds <b>1–4</b>. We utilized the minimum broth dilution method, electron microscopy, and membrane integrity assays to demonstrate that these compounds inhibit the growth of MRSA by disrupting cell wall and membrane structures. Additionally, crystal violet staining confirmed their efficacy in disrupting mature biofilms. In a murine model of bacteremia, the tested compounds <b>1–4</b> demonstrated a reduction in septic symptoms and exhibited favorable biosafety profiles, with compound <b>1</b> showing the most significant antibacterial effects. Transcriptomic analysis indicated that compound <b>1</b> disrupts peptidoglycan synthesis and interferes with the metabolism of cell wall precursors. Furthermore, it modulates the expression of genes associated with ion transport and membrane-related metabolic enzymes, thereby compromising the integrity of both the cell wall and the cytoplasmic membrane. In conclusion, this study systematically characterizes the anti-MRSA activity of the diterpenoid components derived from S. <i>orientalis</i> and identifies key biological processes and gene expression changes linked to their effects, and presents a promising new strategy for the development of natural anti-MRSA pharmaceuticals.
DOI: 10.6084/m9.figshare.30577009.v1
title: Targeting methicillin-resistant <i>staphylococcus aureus</i>: The comprehensive action of ent-kaurane diterpenoids on bacterial integrity

description: Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) represents a considerable challenge to global health owing to its resistance to antibiotics. In our prior research, we identified four ent-kaurane diterpenoids (compounds <b>1-4</b>) isolated from <i>Siegesbeckia orientalis</i> L. which exhibited anti-MRSA activity. Nevertheless, the precise mechanisms by which these compounds exert their effects remain to be fully elucidated. This study aims to comprehensively evaluate the anti-MRSA properties and explore the biological processes associated with the activity of compounds <b>1-4</b>. We utilized the minimum broth dilution method, electron microscopy, and membrane integrity assays to demonstrate that these compounds inhibit the growth of MRSA by disrupting cell wall and membrane structures. Additionally, crystal violet staining confirmed their efficacy in disrupting mature biofilms. In a murine model of bacteremia, the tested compounds <b>1-4</b> demonstrated a reduction in septic symptoms and exhibited favorable biosafety profiles, with compound <b>1</b> showing the most significant antibacterial effects. Transcriptomic analysis indicated that compound <b>1</b> disrupts peptidoglycan synthesis and interferes with the metabolism of cell wall precursors. Furthermore, it modulates the expression of genes associated with ion transport and membrane-related metabolic enzymes, thereby compromising the integrity of both the cell wall and the cytoplasmic membrane. In conclusion, this study systematically characterizes the anti-MRSA activity of the diterpenoid components derived from S. <i>orientalis</i> and identifies key biological processes and gene expression changes linked to their effects, and presents a promising new strategy for the development of natural anti-MRSA pharmaceuticals.
DOI: 10.6084/m9.figshare.29464971
title: <i>Leishmania mexicana</i> pathogenicity requires flagellar assembly but not motility

description: Protists of the order Trypanosomatida possess a single multifunctional flagellum, which powers cellular displacement and mediates attachment to tissues of the arthropod vector. The kinetoplastid flagellar cytoskeleton consists of a nine-microtubule doublet axoneme; further structural elaborations, which can vary between species and life cycle stages, include the assembly of axonemal dynein complexes, a pair of singlet microtubules and the extra-axonemal paraflagellar rod. The intracellular amastigote forms of <i>Leishmania</i> spp. build a short, non-motile cilium whose function has remained enigmatic. Here, we used a panel of 25 barcoded promastigote cell lines, including mutants lacking genes encoding flagellar assembly proteins, axonemal proteins required for normal motility, or flagellar membrane proteins to examine how these defects impact on their virulence in macrophages and mice. Mutants lacking the intraflagellar transport (IFT) protein 88 were avirulent indicating that assembly of a flagellum is necessary to allow for <i>Leishmania</i> survival in a mammalian host. A similarly severe loss of virulence was observed upon deletion of <i>BBS2</i>, a core component of the BBSome complex, which may act as a cargo adapter for IFT. By contrast, promastigotes that were unable to beat their flagella due to loss of core axonemal proteins could establish and sustain an infection and only showed a small reduction of parasite burden <i>in vivo</i> compared to the parental cell lines. These results confirm that flagellar motility is not necessary for mammalian infection, but flagellum assembly and the integrity of the BBSome are essential for pathogenicity.
DOI: 10.6084/m9.figshare.29464971.v1
title: <i>Leishmania mexicana</i> pathogenicity requires flagellar assembly but not motility

description: Protists of the order Trypanosomatida possess a single multifunctional flagellum, which powers cellular displacement and mediates attachment to tissues of the arthropod vector. The kinetoplastid flagellar cytoskeleton consists of a nine-microtubule doublet axoneme; further structural elaborations, which can vary between species and life cycle stages, include the assembly of axonemal dynein complexes, a pair of singlet microtubules and the extra-axonemal paraflagellar rod. The intracellular amastigote forms of <i>Leishmania</i> spp. build a short, non-motile cilium whose function has remained enigmatic. Here, we used a panel of 25 barcoded promastigote cell lines, including mutants lacking genes encoding flagellar assembly proteins, axonemal proteins required for normal motility, or flagellar membrane proteins to examine how these defects impact on their virulence in macrophages and mice. Mutants lacking the intraflagellar transport (IFT) protein 88 were avirulent indicating that assembly of a flagellum is necessary to allow for <i>Leishmania</i> survival in a mammalian host. A similarly severe loss of virulence was observed upon deletion of <i>BBS2</i>, a core component of the BBSome complex, which may act as a cargo adapter for IFT. By contrast, promastigotes that were unable to beat their flagella due to loss of core axonemal proteins could establish and sustain an infection and only showed a small reduction of parasite burden <i>in vivo</i> compared to the parental cell lines. These results confirm that flagellar motility is not necessary for mammalian infection, but flagellum assembly and the integrity of the BBSome are essential for pathogenicity.
DOI: 10.6084/m9.figshare.30621841
title: Genome-wide identification and functional characterization of RxLR effectors in <i>Phytophthora cinnamomi</i> infecting <i>Carya cathayensis</i> Sarg

description: <i>Phytophthora cinnamomi</i> is a globally distributed oomycete pathogen capable of infecting over 5,000 plant species, causing devastating root rot and stem canker diseases with significant agricultural and ecological impacts. Similar to other <i>Phytophthora</i> species, <i>P. cinnamomi</i> secretes RxLR effectors to suppress host immunity and facilitate infection. Here, we present a high-quality genome assembly of <i>P. cinnamomi</i> strain ST402 isolated from an economically important Chinese hickory (<i>Carya cathayensis</i> Sarg.), revealing 146 putative RxLR effectors. Transcriptomic profiling during the early infection stages (0–36 h post-inoculation) identified 66 differentially expressed RxLR effectors, with 4 highly induced candidates (PciRxLR1, PciRxLR21, PciRxLR57, and PciRxLR69) demonstrating cell death suppression activity against pathogen-associated molecular patterns (PAMPs) and promoting <i>Phytophthora</i> pathogenicity in <i>Nicotiana benthamiana</i>. Subcellular localization revealed distinct nuclear and cytoplasmic targeting patterns of these effectors. Our findings provide critical insights into the molecular mechanisms underlying <i>P. cinnamomi</i> virulence and lay the foundation for developing targeted control strategies against this destructive pathogen.
DOI: 10.6084/m9.figshare.30621841.v2
title: Genome-wide identification and functional characterization of RxLR effectors in <i>Phytophthora cinnamomi</i> infecting <i>Carya cathayensis</i> Sarg

description: <i>Phytophthora cinnamomi</i> is a globally distributed oomycete pathogen capable of infecting over 5,000 plant species, causing devastating root rot and stem canker diseases with significant agricultural and ecological impacts. Similar to other <i>Phytophthora</i> species, <i>P. cinnamomi</i> secretes RxLR effectors to suppress host immunity and facilitate infection. Here, we present a high-quality genome assembly of <i>P. cinnamomi</i> strain ST402 isolated from an economically important Chinese hickory (<i>Carya cathayensis</i> Sarg.), revealing 146 putative RxLR effectors. Transcriptomic profiling during the early infection stages (0–36 h post-inoculation) identified 66 differentially expressed RxLR effectors, with 4 highly induced candidates (PciRxLR1, PciRxLR21, PciRxLR57, and PciRxLR69) demonstrating cell death suppression activity against pathogen-associated molecular patterns (PAMPs) and promoting <i>Phytophthora</i> pathogenicity in <i>Nicotiana benthamiana</i>. Subcellular localization revealed distinct nuclear and cytoplasmic targeting patterns of these effectors. Our findings provide critical insights into the molecular mechanisms underlying <i>P. cinnamomi</i> virulence and lay the foundation for developing targeted control strategies against this destructive pathogen.
DOI: 10.6084/m9.figshare.28099834
title: Effect of COVID-19 infection on thyroid function status and clinical indexes among hypothyroid outpatients

description: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly, leading to an Omicron outbreak in Shanghai in mid-December after adjustments to the Coronavirus Disease 2019 (COVID-19) control strategy. To investigate the impact of COVID-19 infection among hypothyroid patients, we gathered data on the hypothyroid outpatients with COVID-19 infection during this time at the Thyroid Disease Center (TDC) of Shanghai Central Hospital. Patients were divided into two groups based on whether their hypothyroidism was caused by Hashimoto’s Thyroiditis (HT): the HT and the non-HT group. We assessed the differences between pre-infection and clinical follow-up at one month (day (D) 30) and three months (D90) after COVID-19 infection. In HT group, thyroid-stimulating hormone (TSH) levels decreased significantly compared to pre-infection levels (<i>p</i> = 0.013), while free triiodothyronine (FT3) levels increased at D90 compared to both D30 post-infection and pre-infection levels (<i>p</i> &lt; 0.001 and <i>p</i> = 0.005). Hemoglobin levels also increased after COVID-19 infection (<i>p</i> = 0.033). For non-HT patients, FT3 levels increased at D30 compared to pre-infection levels (<i>p</i> = 0.017). Moreover, inactivated SARS-CoV-2 vaccination can preserve thyroid function stability in patients with hypothyroidism.
DOI: 10.6084/m9.figshare.28099834.v1
title: Effect of COVID-19 infection on thyroid function status and clinical indexes among hypothyroid outpatients

description: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly, leading to an Omicron outbreak in Shanghai in mid-December after adjustments to the Coronavirus Disease 2019 (COVID-19) control strategy. To investigate the impact of COVID-19 infection among hypothyroid patients, we gathered data on the hypothyroid outpatients with COVID-19 infection during this time at the Thyroid Disease Center (TDC) of Shanghai Central Hospital. Patients were divided into two groups based on whether their hypothyroidism was caused by Hashimoto’s Thyroiditis (HT): the HT and the non-HT group. We assessed the differences between pre-infection and clinical follow-up at one month (day (D) 30) and three months (D90) after COVID-19 infection. In HT group, thyroid-stimulating hormone (TSH) levels decreased significantly compared to pre-infection levels (<i>p</i> = 0.013), while free triiodothyronine (FT3) levels increased at D90 compared to both D30 post-infection and pre-infection levels (<i>p</i> &lt; 0.001 and <i>p</i> = 0.005). Hemoglobin levels also increased after COVID-19 infection (<i>p</i> = 0.033). For non-HT patients, FT3 levels increased at D30 compared to pre-infection levels (<i>p</i> = 0.017). Moreover, inactivated SARS-CoV-2 vaccination can preserve thyroid function stability in patients with hypothyroidism.
DOI: 10.6084/m9.figshare.30621841.v1
title: Genome-wide identification and functional characterization of RxLR effectors in <i>Phytophthora cinnamomi</i> infecting <i>carya cathayensis</i> Sarg

description: <i>Phytophthora cinnamomi</i> is a globally distributed oomycete pathogen capable of infecting over 5,000 plant species, causing devastating root rot and stem canker diseases with significant agricultural and ecological impacts. Similar to other <i>Phytophthora</i> species, <i>P. cinnamomi</i> secretes RxLR effectors to suppress host immunity and facilitate infection. Here, we present a high-quality genome assembly of <i>P. cinnamomi</i> strain ST402 isolated from an economically important Chinese hickory (<i>Carya cathayensis</i> Sarg.), revealing 146 putative RxLR effectors. Transcriptomic profiling during early infection stages (0-36 h post-inoculation) identified 66 differentially expressed RxLR effectors, with 4 highly induced candidates (PciRxLR1, PciRxLR21, PciRxLR57 and PciRxLR69) demonstrating cell death suppression activity against pathogen-associated molecular patterns (PAMPs) and promoting <i>Phytophthora</i> pathogenicity in <i>Nicotiana benthamiana</i>. Subcellular localization revealed distinct nuclear and cytoplasmic targeting patterns of these effectors. Our findings provide critical insights into molecular mechanisms underlying <i>P. cinnamomi</i> virulence and lay the foundation for developing targeted control strategies against this destructive pathogen.
DOI: 10.6084/m9.figshare.30657246
title: Epidemiology, evolution, and biological characteristics of avian influenza A (H11) viruses from wild birds

description: H11 subtype avian influenza viruses (AIVs) have been identified in both wild and domestic birds. H11N9 viruses from wild birds provided the NA gene to human H7N9 virus in 2013 in China, which caused five waves of human infections. During active surveillance in wild birds in China, 17 H11 viruses were isolated between December 2022 and January 2024, including six H11N1, one H11N2, one H11N3, and nine H11N9. The epidemiology of H11 subtype viruses in public databases revealed that they distributed across seven continents, and more than 54.9% of H11 viruses originated from wild Anseriformes. Phylogenetic analysis of the HA genes indicated that H11 viruses were classified into Eurasian and North American lineages, and our isolates belonged to the Eurasian lineage. Bayesian phylogeographic analysis suggested that Bangladesh served as a crucial geographical transmission center for H11 viruses in Eurasian lineage. Reassortment indicated that the H11 isolates in the study underwent complex genomic recombination with various subtype AIVs circulating in wild and domestic birds, including the clade 2.3.4.4b H5N1 highly pathogenic viruses, and formed seven genotypes. Notably, 17 H11 isolates acquired several mutations associated with enhanced human-type receptor binding in HA (S137A) and increased mammalian virulence in PB1 (D3V, D622G), PB1-F2 (N66S), M1 (N30D, I43M, T215A), and NS1 (P42S, I106M). Seven representative viruses exhibited dual receptor binding specificity and could infect mice directly without prior adaptation. These findings highlight the potential public health risks posed by H11 viruses from wild birds and emphasize the necessity of enhancing routine surveillance.
DOI: 10.6084/m9.figshare.30657246.v2
title: Epidemiology, evolution, and biological characteristics of avian influenza A (H11) viruses from wild birds

description: H11 subtype avian influenza viruses (AIVs) have been identified in both wild and domestic birds. H11N9 viruses from wild birds provided the NA gene to human H7N9 virus in 2013 in China, which caused five waves of human infections. During active surveillance in wild birds in China, 17 H11 viruses were isolated between December 2022 and January 2024, including six H11N1, one H11N2, one H11N3, and nine H11N9. The epidemiology of H11 subtype viruses in public databases revealed that they distributed across seven continents, and more than 54.9% of H11 viruses originated from wild Anseriformes. Phylogenetic analysis of the HA genes indicated that H11 viruses were classified into Eurasian and North American lineages, and our isolates belonged to the Eurasian lineage. Bayesian phylogeographic analysis suggested that Bangladesh served as a crucial geographical transmission center for H11 viruses in Eurasian lineage. Reassortment indicated that the H11 isolates in the study underwent complex genomic recombination with various subtype AIVs circulating in wild and domestic birds, including the clade 2.3.4.4b H5N1 highly pathogenic viruses, and formed seven genotypes. Notably, 17 H11 isolates acquired several mutations associated with enhanced human-type receptor binding in HA (S137A) and increased mammalian virulence in PB1 (D3V, D622G), PB1-F2 (N66S), M1 (N30D, I43M, T215A), and NS1 (P42S, I106M). Seven representative viruses exhibited dual receptor binding specificity and could infect mice directly without prior adaptation. These findings highlight the potential public health risks posed by H11 viruses from wild birds and emphasize the necessity of enhancing routine surveillance.
DOI: 10.6084/m9.figshare.30299965
title: Iron metabolism contributes to virulence by enhancing serum resistance in the emerging high-risk clone ST15 CRKP

description: ST15 has become one of the most common sequence types of carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) in China; however, the characteristics of ST15 CRKP remains elusive. This study included a total of 72 unique CRKP isolates, comprising ST15, ST11, ST307, and ST2237, collected from an intensive care unit between 2019 and 2022 to investigate the clinical and biological characteristics as well as the virulence of ST15 CRKP. Whole genome sequencing for 72 CRKP strains and transcriptome sequencing of ST11 and ST15 CRKP after serum exposure was also performed. The virulence of ST15 was similar to that of ST11-KL47, which carries the <i>rmpA2</i> and aerobactin virulence genes, and higher than that of ST11-KL10 and ST307. This may be attributed to its serum resistance. Whole-genome sequencing revealed that genes related to iron uptake (<i>sitA/C/D</i>), the type VI secretion system, and adherence were associated with the serum resistance of ST15. Furthermore, transcriptomic analysis showed that ST15 CRKP strains upregulated genes associated with iron transport and metabolism upon serum exposure. The effect of iron on serum resistance in ST15 was confirmed by supplementing with FeSO<sub>4</sub> and FeCl<sub>3</sub>. Iron metabolism contributes to virulence by enhancing serum resistance in the emerging high-risk clone ST15 CRKP, with <i>sitA/C/D</i> potentially serving as key virulence genes.
DOI: 10.6084/m9.figshare.30299965.v1
title: Iron metabolism contributes to virulence by enhancing serum resistance in the emerging high-risk clone ST15 CRKP

description: ST15 has become one of the most common sequence types of carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) in China; however, the characteristics of ST15 CRKP remains elusive. This study included a total of 72 unique CRKP isolates, comprising ST15, ST11, ST307, and ST2237, collected from an intensive care unit between 2019 and 2022 to investigate the clinical and biological characteristics as well as the virulence of ST15 CRKP. Whole genome sequencing for 72 CRKP strains and transcriptome sequencing of ST11 and ST15 CRKP after serum exposure was also performed. The virulence of ST15 was similar to that of ST11-KL47, which carries the <i>rmpA2</i> and aerobactin virulence genes, and higher than that of ST11-KL10 and ST307. This may be attributed to its serum resistance. Whole-genome sequencing revealed that genes related to iron uptake (<i>sitA/C/D</i>), the type VI secretion system, and adherence were associated with the serum resistance of ST15. Furthermore, transcriptomic analysis showed that ST15 CRKP strains upregulated genes associated with iron transport and metabolism upon serum exposure. The effect of iron on serum resistance in ST15 was confirmed by supplementing with FeSO<sub>4</sub> and FeCl<sub>3</sub>. Iron metabolism contributes to virulence by enhancing serum resistance in the emerging high-risk clone ST15 CRKP, with <i>sitA/C/D</i> potentially serving as key virulence genes.
DOI: 10.6084/m9.figshare.30657246.v1
title: Epidemiology, evolution, and biological characteristics of avian influenza a (H11) viruses from wild birds

description: H11 subtype avian influenza viruses (AIVs) have been identified in both wild and domestic birds. H11N9 viruses from wild birds provided the NA gene to human H7N9 virus in 2013 in China, which caused five waves of human infections. During active surveillance in wild birds in China, 17 H11 viruses were isolated between December 2022 and January 2024, including six H11N1, one H11N2, one H11N3, and nine H11N9. The epidemiology of H11 subtype viruses in public databases revealed that they distributed across seven continents, and more than 54.9% of H11 viruses originated from wild Anseriformes. Phylogenetic analysis of the HA genes indicated that H11 viruses were classified into Eurasian and North American lineages, and our isolates belonged to the Eurasian lineage. Bayesian phylogeographic analysis suggested that Bangladesh served as a crucial geographical transmission center for H11 viruses in Eurasian lineage. Reassortment indicated that the H11 isolates in the study underwent complex genomic recombination with various subtype AIVs circulating in wild and domestic birds, including the clade 2.3.4.4b H5N1 highly pathogenic viruses, and formed seven genotypes. Notably, 17 H11 isolates acquired several mutations associated with enhanced human-type receptor binding in HA (S137A) and increased mammalian virulence in PB1 (D3V, D622G), PB1-F2 (N66S), M1 (N30D, I43M, T215A), and NS1 (P42S, I106M). Seven representative viruses exhibited dual receptor binding specificity and could infect mice directly without prior adaptation. These findings highlight the potential public health risks posed by H11 viruses from wild birds and emphasize the necessity of enhancing routine surveillance.