cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.19829478.v2
title: Gene essentiality profiling reveals a novel determinant of stresses preventing protein aggregation in <i>Salmonella</i>

description: Adaptation to various stresses during infection is important for <i>Salmonella</i> Typhimurium virulence, while the fitness determinants under infection-relevant stress conditions remain unknown. Here, we simulated conditions <i>Salmonella</i> encountered within the host or in the environment by 15 individual stresses as well as two model cell lines (epithelium and macrophage) to decipher the genes and pathways required for fitness. By high-resolution Tn-seq analysis, a total of 1242 genes were identified as essential for fitness under at least one stress condition. The comparative analysis of fitness determinants in 17 stress conditions indicated the essentiality of genes varied in different mimicking host niches. A total of 12 genes were identified as fitness determinants in all stress conditions, including <i>recB</i>, <i>recC</i>, and <i>xseA</i> (encode three exonuclease subunits necessary for DNA recombination repair) and a novel essential fitness gene <i>yheM</i>. YheM is a putative sulfurtransferase subunit that is responsible for tRNA modification, and our results showed that <i>Salmonella</i> lacking <i>yheM</i> accumulated more aggregates of endogenous protein than wild-type. Moreover, we established a scoring scheme for sRNA essentiality analysis and found STnc2080 of unknown function was essential for resistance to LL-37. In summary, we systematically dissected <i>Salmonella</i> gene essentiality profiling and demonstrated the general and specific adaptive requirements in infection-relevant niches. Our data not only provide valuable insights on how <i>Salmonella</i> responds to environmental stresses during infections but also highlight the potential clinical application of fitness determinants in vaccine development.
DOI: 10.15468/dl.h582bm
title: Occurrence Download

description: A dataset containing 659 species occurrences available in GBIF matching the query:
{
 "and" : [
 "TaxonKey is Graphium",
 "HasCoordinate is true"
 ]
}

 The dataset includes 659 records from 87 constituent datasets; see https://api.gbif.org/v1/occurrence/download/0040897-251025141854904/datasets/export for details.
 
Data from some individual datasets included in this download may be licensed under less restrictive terms.
DOI: 10.6084/m9.figshare.19431365
title: Persistence of an epidemic cluster of <i>Rhodotorula mucilaginosa</i> in multiple geographic regions in China and the emergence of a 5-flucytosine resistant clone

description: <i>Rhodotorula mucilaginosa</i>, an environmental yeast widely used in industry and agriculture, is also an opportunistic pathogen resistant to multi-antifungals. During the national surveillance in China, <i>R. mucilaginosa</i> has been documented from various hospitals and regions. At present, the molecular epidemiology of invasive infections caused by <i>R. mucilaginosa</i> and their resistance profiles to antifungals were unknown. Here we collected 49 strains from four hospitals located in different geographic regions from 2009 to 2019 in China, determined their genotypes using different molecular markers and quantified susceptibilities to various antifungals. Sequencing of ITS and D1/D2 regions in rDNA indicated that 73.5% (36/49) of clinical strains belong to same sequence type (rDNA type 2). Microsatellite (MT) genotyping with 15 (recently developed) tandem repeat loci identified 5 epidemic MT types, which accounted for 44.9% (22/49) of clinical strains, as well as 27 sporadic MT types. Microsatellite data indicated that the presence of an epidemic cluster including 35 strains (71.4%) repeatedly isolated in four hospitals for eight years. Single nucleotide variants (SNVs) from the whole genome sequence data also supported the clustering of these epidemic strains due to low pairwise distance. In addition, phylogenetic analysis of SNVs from these clinical strains, together with environmental and animal strains showed that the closely related epidemic cluster strains may be opportunistic, zoonotic pathogens. Also, molecular data indicated a possible clonal transmission of pan echinocandins-azoles-5-flucytosine resistant <i>R. mucilaginosa</i> strains in hospital H01. Our study demonstrated that <i>R. mucilaginosa</i> is a multi-drug resistant pathogen with the ability to cause nosocomial infection.
DOI: 10.6084/m9.figshare.19431365.v2
title: Persistence of an epidemic cluster of <i>Rhodotorula mucilaginosa</i> in multiple geographic regions in China and the emergence of a 5-flucytosine resistant clone

description: <i>Rhodotorula mucilaginosa</i>, an environmental yeast widely used in industry and agriculture, is also an opportunistic pathogen resistant to multi-antifungals. During the national surveillance in China, <i>R. mucilaginosa</i> has been documented from various hospitals and regions. At present, the molecular epidemiology of invasive infections caused by <i>R. mucilaginosa</i> and their resistance profiles to antifungals were unknown. Here we collected 49 strains from four hospitals located in different geographic regions from 2009 to 2019 in China, determined their genotypes using different molecular markers and quantified susceptibilities to various antifungals. Sequencing of ITS and D1/D2 regions in rDNA indicated that 73.5% (36/49) of clinical strains belong to same sequence type (rDNA type 2). Microsatellite (MT) genotyping with 15 (recently developed) tandem repeat loci identified 5 epidemic MT types, which accounted for 44.9% (22/49) of clinical strains, as well as 27 sporadic MT types. Microsatellite data indicated that the presence of an epidemic cluster including 35 strains (71.4%) repeatedly isolated in four hospitals for eight years. Single nucleotide variants (SNVs) from the whole genome sequence data also supported the clustering of these epidemic strains due to low pairwise distance. In addition, phylogenetic analysis of SNVs from these clinical strains, together with environmental and animal strains showed that the closely related epidemic cluster strains may be opportunistic, zoonotic pathogens. Also, molecular data indicated a possible clonal transmission of pan echinocandins-azoles-5-flucytosine resistant <i>R. mucilaginosa</i> strains in hospital H01. Our study demonstrated that <i>R. mucilaginosa</i> is a multi-drug resistant pathogen with the ability to cause nosocomial infection.
DOI: 10.6084/m9.figshare.19613915.v2
title: Molecular epidemiology of human Borna disease virus 1 infection revisited

description: Borna disease virus 1 (BoDV-1) strains attracted public interest by recently reported rare fatal encephalitis cases in Germany. Previously, human BoDV-1 infection was suggested to contribute to psychiatric diseases. Clinical outcomes (encephalitis vs. psychiatric disease) and epidemiology (zoonotic vs. human-to-human transmission) are still controversial. Here, phylogenetic analyses of 18 human and 4 laboratory strains revealed close genomic homologies both in distant geographical regions, and different clinical entities. Single unique amino acid mutations substantiated the authenticity of human strains. No matching was found with those of shrew strains in the same cluster 4, arguing against zoonosis. Opposite epidemiology concepts should be equally considered.
DOI: 10.6084/m9.figshare.19419280
title: The novel fosfomycin resistance gene fosY is present on a genomic island in CC1 methicillin-resistant <i>Staphylococcus aureus</i>

description: Fosfomycin has gained attention as a combination therapy for methicillin-resistant <i>Staphylococcus aureus</i> infections. Hence, the detection of novel fosfomycin-resistance mechanisms in <i>S. aureus</i> is important. Here, the minimal inhibitory concentrations (MICs) of fosfomycin in CC1 methicillin-resistant <i>S. aureus</i> were determined. The pangenome analysis and comparative genomics were used to analyse CC1 MRSA. The gene function was confirmed by cloning the gene into pTXΔ. A phylogenetic tree was constructed to determine the clustering of the CC1 strains of <i>S. aureus.</i> We identified a novel gene, designated <i>fosY</i>, that confers fosfomycin resistance in <i>S. aureus</i>. The FosY protein is a putative bacillithiol transferase enzyme sharing 65.9–77.5% amino acid identity with FosB and FosD, respectively. The function of <i>fosY</i> in decreasing fosfomycin susceptibility was confirmed by cloning it into pTXΔ. The pTX-<i>fosY</i> transformant exhibited a 16-fold increase in fosfomycin MIC. The bioinformatic analysis showed that <i>fosY</i> is in a novel genomic island designated RI<i><sub>fosY</sub></i> (for “resistance island carrying <i>fosY</i>”) that originated from other species. The global phylogenetic tree of ST1 MRSA displayed this <i>fosY</i>-positive ST1 clone, originating from different regions, in the same clade. The novel resistance gene in the fos family, <i>fosY</i>, and a genomic island, RI<i><sub>fosY</sub></i>, can promote cross-species gene transfer and confer resistance to CC1 MRSA causing the failure of clinical treatment. This emphasises the importance of genetic surveillance of resistance genes among MRSA isolates.
DOI: 10.6084/m9.figshare.19419280.v2
title: The novel fosfomycin resistance gene fosY is present on a genomic island in CC1 methicillin-resistant <i>Staphylococcus aureus</i>

description: Fosfomycin has gained attention as a combination therapy for methicillin-resistant <i>Staphylococcus aureus</i> infections. Hence, the detection of novel fosfomycin-resistance mechanisms in <i>S. aureus</i> is important. Here, the minimal inhibitory concentrations (MICs) of fosfomycin in CC1 methicillin-resistant <i>S. aureus</i> were determined. The pangenome analysis and comparative genomics were used to analyse CC1 MRSA. The gene function was confirmed by cloning the gene into pTXΔ. A phylogenetic tree was constructed to determine the clustering of the CC1 strains of <i>S. aureus.</i> We identified a novel gene, designated <i>fosY</i>, that confers fosfomycin resistance in <i>S. aureus</i>. The FosY protein is a putative bacillithiol transferase enzyme sharing 65.9–77.5% amino acid identity with FosB and FosD, respectively. The function of <i>fosY</i> in decreasing fosfomycin susceptibility was confirmed by cloning it into pTXΔ. The pTX-<i>fosY</i> transformant exhibited a 16-fold increase in fosfomycin MIC. The bioinformatic analysis showed that <i>fosY</i> is in a novel genomic island designated RI<i><sub>fosY</sub></i> (for “resistance island carrying <i>fosY</i>”) that originated from other species. The global phylogenetic tree of ST1 MRSA displayed this <i>fosY</i>-positive ST1 clone, originating from different regions, in the same clade. The novel resistance gene in the fos family, <i>fosY</i>, and a genomic island, RI<i><sub>fosY</sub></i>, can promote cross-species gene transfer and confer resistance to CC1 MRSA causing the failure of clinical treatment. This emphasises the importance of genetic surveillance of resistance genes among MRSA isolates.
DOI: 10.6084/m9.figshare.19613915
title: Molecular epidemiology of human Borna disease virus 1 infection revisited

description: Borna disease virus 1 (BoDV-1) strains attracted public interest by recently reported rare fatal encephalitis cases in Germany. Previously, human BoDV-1 infection was suggested to contribute to psychiatric diseases. Clinical outcomes (encephalitis vs. psychiatric disease) and epidemiology (zoonotic vs. human-to-human transmission) are still controversial. Here, phylogenetic analyses of 18 human and 4 laboratory strains revealed close genomic homologies both in distant geographical regions, and different clinical entities. Single unique amino acid mutations substantiated the authenticity of human strains. No matching was found with those of shrew strains in the same cluster 4, arguing against zoonosis. Opposite epidemiology concepts should be equally considered.
DOI: 10.6084/m9.figshare.20226769
title: Pulmonary lesions following inoculation with the SARS-CoV-2 Omicron BA.1 (B.1.1.529) variant in Syrian golden hamsters

description: The Omicron BA.1 (B.1.1.529) SARS-CoV-2 variant is characterized by a high number of mutations in the viral genome, associated with immune escape and increased viral spread. It remains unclear whether milder COVID-19 disease progression observed after infection with Omicron BA.1 in humans is due to reduced pathogenicity of the virus or due to pre-existing immunity from vaccination or previous infection. Here, we inoculated hamsters with Omicron BA.1 to evaluate pathogenicity and kinetics of viral shedding, compared to Delta (B.1.617.2) and to animals re-challenged with Omicron BA.1 after previous SARS-CoV-2 614G infection. Omicron BA.1 infected animals showed reduced clinical signs, pathological changes, and viral shedding, compared to Delta-infected animals, but still showed gross- and histopathological evidence of pneumonia. Pre-existing immunity reduced viral shedding and protected against pneumonia. Our data indicate that the observed decrease of disease severity is in part due to intrinsic properties of the Omicron BA.1 variant.
DOI: 10.6084/m9.figshare.20226769.v2
title: Pulmonary lesions following inoculation with the SARS-CoV-2 Omicron BA.1 (B.1.1.529) variant in Syrian golden hamsters

description: The Omicron BA.1 (B.1.1.529) SARS-CoV-2 variant is characterized by a high number of mutations in the viral genome, associated with immune escape and increased viral spread. It remains unclear whether milder COVID-19 disease progression observed after infection with Omicron BA.1 in humans is due to reduced pathogenicity of the virus or due to pre-existing immunity from vaccination or previous infection. Here, we inoculated hamsters with Omicron BA.1 to evaluate pathogenicity and kinetics of viral shedding, compared to Delta (B.1.617.2) and to animals re-challenged with Omicron BA.1 after previous SARS-CoV-2 614G infection. Omicron BA.1 infected animals showed reduced clinical signs, pathological changes, and viral shedding, compared to Delta-infected animals, but still showed gross- and histopathological evidence of pneumonia. Pre-existing immunity reduced viral shedding and protected against pneumonia. Our data indicate that the observed decrease of disease severity is in part due to intrinsic properties of the Omicron BA.1 variant.
DOI: 10.6084/m9.figshare.19431590
title: Clinical efficacy and safety of interleukin-6 receptor antagonists (tocilizumab and sarilumab) in patients with COVID-19: a systematic review and meta-analysis

description: This study investigated the efficacy and safety of interleukin-6 (IL-6) receptor antagonists with standard care treatment in patients with coronavirus disease 2019 (COVID-19). The randomized controlled trials were identified through systematic searches of electronic databases through February 10, 2022. In total, 17 trials comprising 8,614 patients were included. Compared with exclusive standard care or placebo, IL-6 receptor antagonists with standard of care treatment were associated with a significantly reduced all-cause mortality at 28 days (pooled risk ratios [RR], 0.88; 95% confidence interval (CI), 0.82–0.95; 17 studies) and progression to invasive mechanical ventilation (RR, 0.79; 95% CI, 0.71–0.88; nine studies). Particularly, the subgroup of patients with moderate-to-severe COVID-19 showed a significant mortality benefit (RR, 0.89; 95% CI, 0.81–0.96; four studies) and a reduced risk for mechanical ventilation (RR, 0.80; 95% CI, 0.70–0.91; three studies) with tocilizumab treatment. The frequency of serious adverse events was lower in the tocilizumab treatment group than in the standard of care treatment group (RR, 0.83; 95% CI, 0.71–0.97; 11 studies), with no significant difference in the sarilumab treatment group (RR, 1.12; 95% CI, 0.89–1.40; four studies). Our meta-analysis demonstrated that tocilizumab treatment showed promising results in reducing 28-day mortality and progression to mechanical ventilation in patients with moderate-to-severe COVID-19, without the burden of serious adverse events. <b>Trial registration:</b> PROSPERO: registration number CRD42021294120.
DOI: 10.6084/m9.figshare.19431590.v2
title: Clinical efficacy and safety of interleukin-6 receptor antagonists (tocilizumab and sarilumab) in patients with COVID-19: a systematic review and meta-analysis

description: This study investigated the efficacy and safety of interleukin-6 (IL-6) receptor antagonists with standard care treatment in patients with coronavirus disease 2019 (COVID-19). The randomized controlled trials were identified through systematic searches of electronic databases through February 10, 2022. In total, 17 trials comprising 8,614 patients were included. Compared with exclusive standard care or placebo, IL-6 receptor antagonists with standard of care treatment were associated with a significantly reduced all-cause mortality at 28 days (pooled risk ratios [RR], 0.88; 95% confidence interval (CI), 0.82–0.95; 17 studies) and progression to invasive mechanical ventilation (RR, 0.79; 95% CI, 0.71–0.88; nine studies). Particularly, the subgroup of patients with moderate-to-severe COVID-19 showed a significant mortality benefit (RR, 0.89; 95% CI, 0.81–0.96; four studies) and a reduced risk for mechanical ventilation (RR, 0.80; 95% CI, 0.70–0.91; three studies) with tocilizumab treatment. The frequency of serious adverse events was lower in the tocilizumab treatment group than in the standard of care treatment group (RR, 0.83; 95% CI, 0.71–0.97; 11 studies), with no significant difference in the sarilumab treatment group (RR, 1.12; 95% CI, 0.89–1.40; four studies). Our meta-analysis demonstrated that tocilizumab treatment showed promising results in reducing 28-day mortality and progression to mechanical ventilation in patients with moderate-to-severe COVID-19, without the burden of serious adverse events. <b>Trial registration:</b> PROSPERO: registration number CRD42021294120.
DOI: 10.6084/m9.figshare.19795438
title: ACE2 decoy receptor generated by high-throughput saturation mutagenesis efficiently neutralizes SARS-CoV-2 and its prevalent variants

description: The recent global pandemic was a spillover from the SARS-CoV-2 virus. Viral entry involves the receptor binding domain (RBD) of the viral spike protein interacting with the protease domain (PD) of the cellular receptor, ACE2. We hereby present a comprehensive mutational landscape of the effects of ACE2-PD point mutations on RBD-ACE2 binding using a saturation mutagenesis approach based on microarray-based oligo synthesis and a single-cell screening assay. We observed that changes in glycosylation sites and directly interacting sites of ACE2-PD significantly influenced ACE2-RBD binding. We further engineered an ACE2 decoy receptor with critical point mutations, D30I, L79W, T92N, N322V, and K475F, named C4-1. C4-1 shows a 200-fold increase in neutralization for the SARS-CoV-2 D614G pseudotyped virus compared to wild-type soluble ACE2 and a sevenfold increase in binding affinity to wild-type spike compared to the C-terminal Ig-Fc fused wild-type soluble ACE2. Moreover, C4-1 efficiently neutralized prevalent variants, especially the omicron variant (EC50=16 ng/mL), and rescued monoclonal antibodies, vaccine, and convalescent sera neutralization from viral immune-escaping. We hope to next investigate translating the therapeutic potential of C4-1 for the treatment of SARS-CoV-2.
DOI: 10.6084/m9.figshare.19795438.v2
title: ACE2 decoy receptor generated by high-throughput saturation mutagenesis efficiently neutralizes SARS-CoV-2 and its prevalent variants

description: The recent global pandemic was a spillover from the SARS-CoV-2 virus. Viral entry involves the receptor binding domain (RBD) of the viral spike protein interacting with the protease domain (PD) of the cellular receptor, ACE2. We hereby present a comprehensive mutational landscape of the effects of ACE2-PD point mutations on RBD-ACE2 binding using a saturation mutagenesis approach based on microarray-based oligo synthesis and a single-cell screening assay. We observed that changes in glycosylation sites and directly interacting sites of ACE2-PD significantly influenced ACE2-RBD binding. We further engineered an ACE2 decoy receptor with critical point mutations, D30I, L79W, T92N, N322V, and K475F, named C4-1. C4-1 shows a 200-fold increase in neutralization for the SARS-CoV-2 D614G pseudotyped virus compared to wild-type soluble ACE2 and a sevenfold increase in binding affinity to wild-type spike compared to the C-terminal Ig-Fc fused wild-type soluble ACE2. Moreover, C4-1 efficiently neutralized prevalent variants, especially the omicron variant (EC50=16 ng/mL), and rescued monoclonal antibodies, vaccine, and convalescent sera neutralization from viral immune-escaping. We hope to next investigate translating the therapeutic potential of C4-1 for the treatment of SARS-CoV-2.
DOI: 10.6084/m9.figshare.19390802
title: Identification of a recombinant equine coronavirus in donkey, China

description: Equine coronavirus (ECoV) was first identified in the USA and has been previously described in several countries. In order to test the presence of ECoV in China, we collected 51 small intestinal samples from donkey foals with diarrhoea from a donkey farm in Shandong Province, China between August 2020 and April 2021. Two samples tested positive for ECoV and full-length genome sequences were successfully obtained using next-generation sequencing, one of which was further confirmed by Sanger sequencing. The two strains shared 100% sequence identity at the scale of whole genome. Bioinformatics analyses further showed that the two Chinese strains represent a novel genetic variant of ECoV and shared the highest sequence identity of 97.05% with the first identified ECoV strain – NC99. In addition, it may be a recombinant, with the recombination region around the NS2 gene. To our knowledge, this is the first documented report of ECoV in China, highlighting its risk to horse/donkey breeding. In addition, its potential risk to public health also warrants further investigation.
DOI: 10.6084/m9.figshare.19390802.v2
title: Identification of a recombinant equine coronavirus in donkey, China

description: Equine coronavirus (ECoV) was first identified in the USA and has been previously described in several countries. In order to test the presence of ECoV in China, we collected 51 small intestinal samples from donkey foals with diarrhoea from a donkey farm in Shandong Province, China between August 2020 and April 2021. Two samples tested positive for ECoV and full-length genome sequences were successfully obtained using next-generation sequencing, one of which was further confirmed by Sanger sequencing. The two strains shared 100% sequence identity at the scale of whole genome. Bioinformatics analyses further showed that the two Chinese strains represent a novel genetic variant of ECoV and shared the highest sequence identity of 97.05% with the first identified ECoV strain – NC99. In addition, it may be a recombinant, with the recombination region around the NS2 gene. To our knowledge, this is the first documented report of ECoV in China, highlighting its risk to horse/donkey breeding. In addition, its potential risk to public health also warrants further investigation.