cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.12011181.v2
title: Tropism, pathology, and transmission of equine parvovirus-hepatitis

description: Equine parvovirus-hepatitis (EqPV-H) has recently been associated with cases of Theiler's disease, a form of fulminant hepatic necrosis in horses. To assess whether EqPV-H is the cause of Theiler's disease, we first demonstrated hepatotropism by PCR on tissues from acutely infected horses. We then experimentally inoculated horses with EqPV-H and 8 of 10 horses developed hepatitis. One horse showed clinical signs of liver failure. The onset of hepatitis was temporally associated with seroconversion and a decline in viremia. Liver histology and <i>in situ</i> hybridization showed lymphocytic infiltrates and necrotic EqPV-H-infected hepatocytes. We next investigated potential modes of transmission. Iatrogenic transmission via allogeneic stem cell therapy for orthopedic injuries was previously suggested in a case series of Theiler's disease, and was demonstrated here for the first time. Vertical transmission and mechanical vectoring by horse fly bites could not be demonstrated in this study, potentially due to limited sample size. We found EqPV-H shedding in oral and nasal secretions, and in feces. Importantly, we could demonstrate EqPV-H transmission via oral inoculation with viremic serum. Together, our findings provide additional information that EqPV-H is the likely cause of Theiler's disease and that transmission of EqPV-H occurs via both iatrogenic and natural routes.
DOI: 10.6084/m9.figshare.13029039
title: Genomic epidemiology of emerging ESBL-producing <i>Salmonella</i> Kentucky <i>bla</i><sub>CTX-M-14b</sub> in Europe

description: Global dissemination of ciprofloxacin-resistant <i>Salmonella</i> Kentucky has been observed over the past decades. In recent years, there have been reports of extended-spectrum β-lactamase (ESBL) producing <i>S</i>. Kentucky. Routine surveillance at the European Centre for Disease Prevention and Control (ECDC) detected cases with a ciprofloxacin-resistant <i>S</i>. Kentucky with the ESBL-gene <i>bla</i><sub>CTX-M-14b</sub>. Ensuing research identified 78 cases in 2013–2018 in eight European countries. Compared to other <i>S</i>. Kentucky and non-typhoidal <i>Salmonella</i> infections, reported to the European Surveillance System, these cases were more likely to be elderly and to present urinary-tract infections. Bayesian time-scaled phylogeny on whole genome sequences of isolates from these cases and supplementary isolates from public sequence databases was used to infer the origin and spread of this clone. We dated the origin of the <i>bla</i><sub>CTX-M-14b</sub> clone to approximately 2005 in Northern Africa, most likely in Egypt. The geographic origin predicted by the phylogenetic analysis is consistent with the patients’ travel history. Next to multiple introductions of the clone to Europe from Egypt, our analysis suggests that in some parts of Europe the clone might have formed a stable population, from which further spread has occurred. Comparative genomics indicated that the <i>bla</i><sub>CTX-M-14b</sub> gene is present on the bacterial chromosome, within the type VI secretion system region. The <i>bla</i><sub>CTX-M-14b</sub> gene is integrated downstream of the <i>hcp1</i> gene, on a 2854 bp plasmid fragment containing also IS<i>Ecp1</i>. This is the first report of a chromosomally integrated CTX-M gene in <i>Salmonella</i> spp. in Europe, previous studies having identified similar genes only on plasmids.
DOI: 10.6084/m9.figshare.12905858
title: Molecular characterization of chikungunya virus during the 2019 outbreak in the Democratic Republic of the Congo

description: Early 2019, a chikungunya virus (CHIKV) outbreak hit the Democratic Republic of the Congo (DRC). Though seldomly deadly, this mosquito-borne disease presents as an acute febrile (poly)arthralgia often followed by long-term sequelae. Although <i>Aedes aegypti</i> is the primary vector, an amino acid substitution in the viral envelope gene E1 (A226V) is causing concern as it results in increased transmission by <i>Aedes albopictus</i>, a mosquito with a much wider geographical distribution. Between January and March 2019, we collected human and mosquito samples in Kinshasa and Kongo Central province (Kasangulu and Matadi). Of the patients that were tested within 7 days of symptom onset, 49.7% (87/175) were RT–qPCR positive, while in the mosquito samples CHIKV was found in 1/2 pools in Kinshasa, 5/6 pools in Kasangulu, and 8/26 pools in Matadi. Phylogenetic analysis on whole-genome sequences showed that the circulating strain formed a monophyletic group within the ECSA2 lineage and harboured the A226V mutation. Our sequences did not cluster with sequences from previously reported outbreaks in the DRC nor with other known A226V-containing ECSA2 strains. This indicates a scenario of convergent evolution where A226V was acquired independently in response to a similar selection pressure for transmission by <i>Ae. albopictus</i>. This is in line with our entomological data where we detected <i>Ae. albopictu</i>s more frequently than <i>Ae. aegypti</i> in two out of three affected areas. In conclusion, our findings suggest that CHIKV is adapting to the increased presence of <i>Aedes albopictus</i> in DRC.
DOI: 10.6084/m9.figshare.13029039.v18
title: Genomic epidemiology of emerging ESBL-producing <i>Salmonella</i> Kentucky <i>bla</i><sub>CTX-M-14b</sub> in Europe

description: Global dissemination of ciprofloxacin-resistant <i>Salmonella</i> Kentucky has been observed over the past decades. In recent years, there have been reports of extended-spectrum β-lactamase (ESBL) producing <i>S</i>. Kentucky. Routine surveillance at the European Centre for Disease Prevention and Control (ECDC) detected cases with a ciprofloxacin-resistant <i>S</i>. Kentucky with the ESBL-gene <i>bla</i><sub>CTX-M-14b</sub>. Ensuing research identified 78 cases in 2013–2018 in eight European countries. Compared to other <i>S</i>. Kentucky and non-typhoidal <i>Salmonella</i> infections, reported to the European Surveillance System, these cases were more likely to be elderly and to present urinary-tract infections. Bayesian time-scaled phylogeny on whole genome sequences of isolates from these cases and supplementary isolates from public sequence databases was used to infer the origin and spread of this clone. We dated the origin of the <i>bla</i><sub>CTX-M-14b</sub> clone to approximately 2005 in Northern Africa, most likely in Egypt. The geographic origin predicted by the phylogenetic analysis is consistent with the patients’ travel history. Next to multiple introductions of the clone to Europe from Egypt, our analysis suggests that in some parts of Europe the clone might have formed a stable population, from which further spread has occurred. Comparative genomics indicated that the <i>bla</i><sub>CTX-M-14b</sub> gene is present on the bacterial chromosome, within the type VI secretion system region. The <i>bla</i><sub>CTX-M-14b</sub> gene is integrated downstream of the <i>hcp1</i> gene, on a 2854 bp plasmid fragment containing also IS<i>Ecp1</i>. This is the first report of a chromosomally integrated CTX-M gene in <i>Salmonella</i> spp. in Europe, previous studies having identified similar genes only on plasmids.
DOI: 10.6084/m9.figshare.13488180
title: Loss of orf3b in the circulating SARS-CoV-2 strains

description: The newly emerged betacoronavirus, SARS-CoV-2, causes the COVID-19 pandemic since December 2019 with more than 35 million laboratory confirmed human infections and over one million deaths within nine months. The genome of SARS-CoV-2 continues to evolve during the global transmission with the notable emergence of the spike D614G substitution that enhances infectivity. Some of these viral adaptations may alter not only the infectivity but also viral pathogenesis. Continuous phylogenomic analysis of circulating viral strains and functional investigation of new non-synonymous substitutions may help to understand the evolution of virus, its virulence and transmissibility. Here we describe a loss of an accessory protein orf3b (57 amino acids) in current circulating SARS-CoV-2 strains, contributing around 24% of more than 100,000 complete viral genomes analysed. The loss of 3b is caused by the presence of an early stop codon which is created by an orf3a Q57H substitution. There is an increasing trend in the loss of orf3b which has reached 32% in May 2020. Geographically, loss of 3b is more prevalent in certain countries including Colombia (46%), USA (48%), South Korea (51%), France (66%), Saudi Arabia (72%), Finland (76%) and Egypt (77%). Interestingly, the loss of 3b coincides with the emergence of spike D614G substitution. In addition, we found that truncated orf3b has lost the interferon antagonism compared to the full-length orf3b, suggesting a loss of function by the newly adapted virus. Further investigation of orf3b deletion and spike D614G substitution on virulence and infectivity respectively will provide important insights into SARS-CoV-2 evolution.
DOI: 10.6084/m9.figshare.13029039.v17
title: Genomic epidemiology of emerging ESBL-producing <i>Salmonella</i> Kentucky <i>bla</i><sub>CTX-M-14b</sub> in Europe

description: Global dissemination of ciprofloxacin-resistant <i>Salmonella</i> Kentucky has been observed over the past decades. In recent years, there have been reports of extended-spectrum β-lactamase (ESBL) producing <i>S</i>. Kentucky. Routine surveillance at the European Centre for Disease Prevention and Control (ECDC) detected cases with a ciprofloxacin-resistant <i>S</i>. Kentucky with the ESBL-gene <i>bla</i><sub>CTX-M-14b</sub>. Ensuing research identified 78 cases in 2013–2018 in eight European countries. Compared to other <i>S</i>. Kentucky and non-typhoidal <i>Salmonella</i> infections, reported to the European Surveillance System, these cases were more likely to be elderly and to present urinary-tract infections. Bayesian time-scaled phylogeny on whole genome sequences of isolates from these cases and supplementary isolates from public sequence databases was used to infer the origin and spread of this clone. We dated the origin of the <i>bla</i><sub>CTX-M-14b</sub> clone to approximately 2005 in Northern Africa, most likely in Egypt. The geographic origin predicted by the phylogenetic analysis is consistent with the patients’ travel history. Next to multiple introductions of the clone to Europe from Egypt, our analysis suggests that in some parts of Europe the clone might have formed a stable population, from which further spread has occurred. Comparative genomics indicated that the <i>bla</i><sub>CTX-M-14b</sub> gene is present on the bacterial chromosome, within the type VI secretion system region. The <i>bla</i><sub>CTX-M-14b</sub> gene is integrated downstream of the <i>hcp1</i> gene, on a 2854 bp plasmid fragment containing also IS<i>Ecp1</i>. This is the first report of a chromosomally integrated CTX-M gene in <i>Salmonella</i> spp. in Europe, previous studies having identified similar genes only on plasmids.
DOI: 10.6084/m9.figshare.13488180.v1
title: Loss of orf3b in the circulating SARS-CoV-2 strains

description: The newly emerged betacoronavirus, SARS-CoV-2, causes the COVID-19 pandemic since December 2019 with more than 35 million laboratory confirmed human infections and over one million deaths within nine months. The genome of SARS-CoV-2 continues to evolve during the global transmission with the notable emergence of the spike D614G substitution that enhances infectivity. Some of these viral adaptations may alter not only the infectivity but also viral pathogenesis. Continuous phylogenomic analysis of circulating viral strains and functional investigation of new non-synonymous substitutions may help to understand the evolution of virus, its virulence and transmissibility. Here we describe a loss of an accessory protein orf3b (57 amino acids) in current circulating SARS-CoV-2 strains, contributing around 24% of more than 100,000 complete viral genomes analysed. The loss of 3b is caused by the presence of an early stop codon which is created by an orf3a Q57H substitution. There is an increasing trend in the loss of orf3b which has reached 32% in May 2020. Geographically, loss of 3b is more prevalent in certain countries including Colombia (46%), USA (48%), South Korea (51%), France (66%), Saudi Arabia (72%), Finland (76%) and Egypt (77%). Interestingly, the loss of 3b coincides with the emergence of spike D614G substitution. In addition, we found that truncated orf3b has lost the interferon antagonism compared to the full-length orf3b, suggesting a loss of function by the newly adapted virus. Further investigation of orf3b deletion and spike D614G substitution on virulence and infectivity respectively will provide important insights into SARS-CoV-2 evolution.
DOI: 10.6084/m9.figshare.11418321
title: Transcriptional response to metal starvation in the emerging pathogen <i>Mycoplasma genitalium</i> is mediated by Fur-dependent and –independent regulatory pathways

description: Transition metals participate in numerous enzymatic reactions and they are essential for survival in all living organisms. For this reason, bacterial pathogens have evolved dedicated machineries to effectively compete with their hosts and scavenge metals at the site of infection. In this study, we investigated the mechanisms controlling metal acquisition in the emerging human pathogen <i>Mycoplasma genitalium</i>. We observed a robust transcriptional response to metal starvation, and many genes coding for predicted lipoproteins and ABC-transporters were significantly up-regulated. Transcriptional analysis of a mutant strain lacking a metalloregulator of the Fur family revealed the activation of a full operon encoding a putative metal transporter system and a gene coding for a Histidine-rich lipoprotein (Hrl). We recognized a conserved sequence with dyad symmetry within the promoter region of the Fur-regulated genes. Mutagenesis of the predicted Fur operator within the <i>hrl</i> promoter abrogated Fur- and metal-dependent expression of a reporter gene. Metal starvation still impelled a strong transcriptional response in the <i>fur</i> mutant, demonstrating the existence of Fur-independent regulatory pathways controlling metal homeostasis. Finally, analysis of metal accumulation in the wild-type strain and the <i>fur</i> mutant by ICP-MS revealed an important role of Fur in nickel acquisition.
DOI: 10.6084/m9.figshare.12853706
title: Antibody kinetics in primary- and secondary-care physicians with mild to moderate SARS-CoV-2 infection

description: Three hundred and ninety-seven primary- and secondary-care physicians were tested for the presence of IgG (and IgA) antibodies against SARS-coronavirus-2 with a commercially available ELISA. In 19 of 20 individuals with PCR-proven infection and only mild to moderate symptoms not requiring hospitalization positive IgG levels occurred within two to three weeks. Among the remaining 377 persons without clear-cut evidence of infection, unequivocally positive IgG antibodies were found in only one, showing a surprisingly low prevalence (0.3%, 95% CI: 0.01–1.5) in physicians with likely contacts with infected patients in a region highly affected by the pandemic (Tyrol, Austria).
DOI: 10.6084/m9.figshare.12853706.v1
title: Antibody kinetics in primary- and secondary-care physicians with mild to moderate SARS-CoV-2 infection

description: Three hundred and ninety-seven primary- and secondary-care physicians were tested for the presence of IgG (and IgA) antibodies against SARS-coronavirus-2 with a commercially available ELISA. In 19 of 20 individuals with PCR-proven infection and only mild to moderate symptoms not requiring hospitalization positive IgG levels occurred within two to three weeks. Among the remaining 377 persons without clear-cut evidence of infection, unequivocally positive IgG antibodies were found in only one, showing a surprisingly low prevalence (0.3%, 95% CI: 0.01–1.5) in physicians with likely contacts with infected patients in a region highly affected by the pandemic (Tyrol, Austria).
DOI: 10.6084/m9.figshare.11418321.v3
title: Transcriptional response to metal starvation in the emerging pathogen <i>Mycoplasma genitalium</i> is mediated by Fur-dependent and –independent regulatory pathways

description: Transition metals participate in numerous enzymatic reactions and they are essential for survival in all living organisms. For this reason, bacterial pathogens have evolved dedicated machineries to effectively compete with their hosts and scavenge metals at the site of infection. In this study, we investigated the mechanisms controlling metal acquisition in the emerging human pathogen <i>Mycoplasma genitalium</i>. We observed a robust transcriptional response to metal starvation, and many genes coding for predicted lipoproteins and ABC-transporters were significantly up-regulated. Transcriptional analysis of a mutant strain lacking a metalloregulator of the Fur family revealed the activation of a full operon encoding a putative metal transporter system and a gene coding for a Histidine-rich lipoprotein (Hrl). We recognized a conserved sequence with dyad symmetry within the promoter region of the Fur-regulated genes. Mutagenesis of the predicted Fur operator within the <i>hrl</i> promoter abrogated Fur- and metal-dependent expression of a reporter gene. Metal starvation still impelled a strong transcriptional response in the <i>fur</i> mutant, demonstrating the existence of Fur-independent regulatory pathways controlling metal homeostasis. Finally, analysis of metal accumulation in the wild-type strain and the <i>fur</i> mutant by ICP-MS revealed an important role of Fur in nickel acquisition.
DOI: 10.6084/m9.figshare.11418321.v2
title: Transcriptional response to metal starvation in the emerging pathogen <i>Mycoplasma genitalium</i> is mediated by Fur-dependent and –independent regulatory pathways

description: Transition metals participate in numerous enzymatic reactions and they are essential for survival in all living organisms. For this reason, bacterial pathogens have evolved dedicated machineries to effectively compete with their hosts and scavenge metals at the site of infection. In this study, we investigated the mechanisms controlling metal acquisition in the emerging human pathogen <i>Mycoplasma genitalium</i>. We observed a robust transcriptional response to metal starvation, and many genes coding for predicted lipoproteins and ABC-transporters were significantly up-regulated. Transcriptional analysis of a mutant strain lacking a metalloregulator of the Fur family revealed the activation of a full operon encoding a putative metal transporter system and a gene coding for a Histidine-rich lipoprotein (Hrl). We recognized a conserved sequence with dyad symmetry within the promoter region of the Fur-regulated genes. Mutagenesis of the predicted Fur operator within the <i>hrl</i> promoter abrogated Fur- and metal-dependent expression of a reporter gene. Metal starvation still impelled a strong transcriptional response in the <i>fur</i> mutant, demonstrating the existence of Fur-independent regulatory pathways controlling metal homeostasis. Finally, analysis of metal accumulation in the wild-type strain and the <i>fur</i> mutant by ICP-MS revealed an important role of Fur in nickel acquisition.
DOI: 10.6084/m9.figshare.11999553
title: Live bird markets as evolutionary epicentres of H9N2 low pathogenicity avian influenza viruses in Korea

description: Live bird markets (LBMs) in Korea have been recognized as a reservoir, amplifier, and source of avian influenza viruses (AIVs); however, little was known about the role of LBMs in the epidemiology of AIVs in Korea until recently. Through 10 years of surveillance (2006–2016) we have isolated and sequenced H9N2 viruses in Korean LBMs. To understand how H9N2 evolves and spreads in Korea, a statistical Bayesian phylogenetic model was used. Phylogenetic analysis suggests that three separate introductions of progenitor gene pools, Korean domestic duck-origin and two wild aquatic bird-origin AIVs, contributed to the generation of the five genotypes of H9N2 viruses in Korea. Phylogenetic reconstruction of ecological states infer that the LBMs are where chickens become infected with the virus, with domestic ducks playing a major role in the transmission and evolution of the H9N2 viruses. Three increases in the genetic diversity of H9N2 viruses were observed and coincided with transitions in host species and the locations (domestic farm, LBM, slaughterhouse, and wild aquatic bird habitat) where the viruses were isolated, accompanying genetic reassortment. Following the introduction of a wild aquatic bird-origin AIVs in 2008, six genes of the Korean lineage H9N2 virus were replaced with genes originating from wild aquatic birds, and viruses with this new genotype became predominant in Korean LBMs.
DOI: 10.6084/m9.figshare.11999553.v3
title: Live bird markets as evolutionary epicentres of H9N2 low pathogenicity avian influenza viruses in Korea

description: Live bird markets (LBMs) in Korea have been recognized as a reservoir, amplifier, and source of avian influenza viruses (AIVs); however, little was known about the role of LBMs in the epidemiology of AIVs in Korea until recently. Through 10 years of surveillance (2006–2016) we have isolated and sequenced H9N2 viruses in Korean LBMs. To understand how H9N2 evolves and spreads in Korea, a statistical Bayesian phylogenetic model was used. Phylogenetic analysis suggests that three separate introductions of progenitor gene pools, Korean domestic duck-origin and two wild aquatic bird-origin AIVs, contributed to the generation of the five genotypes of H9N2 viruses in Korea. Phylogenetic reconstruction of ecological states infer that the LBMs are where chickens become infected with the virus, with domestic ducks playing a major role in the transmission and evolution of the H9N2 viruses. Three increases in the genetic diversity of H9N2 viruses were observed and coincided with transitions in host species and the locations (domestic farm, LBM, slaughterhouse, and wild aquatic bird habitat) where the viruses were isolated, accompanying genetic reassortment. Following the introduction of a wild aquatic bird-origin AIVs in 2008, six genes of the Korean lineage H9N2 virus were replaced with genes originating from wild aquatic birds, and viruses with this new genotype became predominant in Korean LBMs.
DOI: 10.6084/m9.figshare.12085149
title: Rsp promotes the transcription of virulence factors in an <i>agr</i>-independent manner in <i>Staphylococcus aureus</i>

description: <i>Staphylococcus aureus</i> is a major human pathogen that causes a great diversity of community- and hospital-acquired infections. Rsp, a member of AraC/XylS family of transcriptional regulators (AFTRs), has been reported to play an important role in the regulation of virulence determinants in <i>S. aureus</i> via an <i>agr</i>-dependent pathway. Here we demonstrated that Rsp could bind to the <i>rsp</i> promoter to positively regulate its own expression. We then constructed an isogenic <i>rsp</i> deletion strain and compared the haemolysis in the wild-type and <i>rsp</i> mutant strains. Our results indicated that the <i>rsp</i> mutant strain displayed decreased haemolytic activity, which was correlated with a dramatic decrease in the expression of <i>hla</i> and <i>psm</i>. Furthermore, we analysed the regulatory effects of Rsp in the <i>agr</i> mutant strain and found that they are <i>agr</i>-independent. Electrophoretic mobility shift assay indicated that Rsp can directly bind to the promoter regions of <i>hla</i> and <i>psm</i>. The mouse model of subcutaneous abscess showed that the <i>rsp</i> mutant strain displayed a significant defect in virulence compared to the wild-type strain. These findings reveal that Rsp positively regulates the virulence of <i>S. aureus</i> by promoting the expression of <i>hla</i> and <i>psm</i> through direct binding to their promoter regions.