cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.14639866.v1
title: Microdiversity of <i>Enterococcus faecalis</i> isolates in cases of infective endocarditis: selection of non-synonymous mutations and large deletions is associated with phenotypic modifications

description: <i>Context</i>: Today, infective endocarditis (IE) caused by <i>Enterococcus faecalis</i> represents 10% of all IE and is marked by its difficult management and the frequency of relapses. Although the precise reasons for that remain to be elucidated, the evolution of the culprit strain under selective pressure through microdiversification could be, at least in part, involved. <i>Material and methods</i>: To further study the <i>in situ</i> genetic microdiversity and its possible phenotypic manifestations in <i>E. faecalis</i> IE, we sequenced and compared multiple isolates from the valves, blood culture and joint fluid of five patients who underwent valvular surgery. Growth rate and early biofilm production of selected isolates were also compared. <i>Results</i>: By sequencing a total of 58 <i>E. faecalis</i> genomes, we detected a considerable genomic microdiversity, not only among strains from different anatomical origins, but also between isolates from the same studied cardiac valves. Interestingly, deletions of thousands of bases including the well-known virulence factors <i>ebpA/B/C</i>, and <i>srtC</i>, as well as other large prophage sequences containing genes coding for proteins implicated in platelet binding (PlbA and PlbB) were evidenced. The study of mutations helped unveil common patterns in genes related to the cell cycle as well as central metabolism, suggesting an evolutionary convergence in these isolates. As expected, such modifications were associated with a significant impact on the <i>in-vitro</i> phenotypic heterogeneity, growth, and early biofilm production. <i>Conclusion</i>: Genome modifications associated with phenotypic variations may allow bacterial adaptation to both antibiotic and immune selective pressures, and thus promote relapses.
DOI: 10.6084/m9.figshare.13582996
title: SARS-CoV-2 genomic characterization and clinical manifestation of the COVID-19 outbreak in Uruguay

description: COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020. We performed a phylogeographic analysis using sequences from our cohort and other studies that indicate a minimum of 23 independent introductions into Uruguay, resulting in five major transmission clusters. Our data suggest that most introductions resulting in chains of transmission originate from other South American countries, with the earliest seeding of the virus in late February 2020, weeks before the borders were closed to all non-citizens and a partial lockdown implemented. Genetic analyses suggest a dominance of S and G clades (G, GH, GR) that make up &gt;90% of the viral strains in our study. In our cohort, lethal outcome of SARS-CoV-2 infection significantly correlated with arterial hypertension, kidney failure, and ICU admission (FDR &lt; 0.01), but not with any mutation in a structural or non-structural protein, such as the spike D614G mutation. Our study contributes genetic, phylodynamic, and clinical correlation data about the exceptionally well-curbed SARS-CoV-2 outbreak in Uruguay, which furthers the understanding of disease patterns and regional aspects of the pandemic in Latin America.
DOI: 10.6084/m9.figshare.13582996.v1
title: SARS-CoV-2 genomic characterization and clinical manifestation of the COVID-19 outbreak in Uruguay

description: COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020. We performed a phylogeographic analysis using sequences from our cohort and other studies that indicate a minimum of 23 independent introductions into Uruguay, resulting in five major transmission clusters. Our data suggest that most introductions resulting in chains of transmission originate from other South American countries, with the earliest seeding of the virus in late February 2020, weeks before the borders were closed to all non-citizens and a partial lockdown implemented. Genetic analyses suggest a dominance of S and G clades (G, GH, GR) that make up &gt;90% of the viral strains in our study. In our cohort, lethal outcome of SARS-CoV-2 infection significantly correlated with arterial hypertension, kidney failure, and ICU admission (FDR &lt; 0.01), but not with any mutation in a structural or non-structural protein, such as the spike D614G mutation. Our study contributes genetic, phylodynamic, and clinical correlation data about the exceptionally well-curbed SARS-CoV-2 outbreak in Uruguay, which furthers the understanding of disease patterns and regional aspects of the pandemic in Latin America.
DOI: 10.6084/m9.figshare.14639866
title: Microdiversity of <i>Enterococcus faecalis</i> isolates in cases of infective endocarditis: selection of non-synonymous mutations and large deletions is associated with phenotypic modifications

description: <i>Context</i>: Today, infective endocarditis (IE) caused by <i>Enterococcus faecalis</i> represents 10% of all IE and is marked by its difficult management and the frequency of relapses. Although the precise reasons for that remain to be elucidated, the evolution of the culprit strain under selective pressure through microdiversification could be, at least in part, involved. <i>Material and methods</i>: To further study the <i>in situ</i> genetic microdiversity and its possible phenotypic manifestations in <i>E. faecalis</i> IE, we sequenced and compared multiple isolates from the valves, blood culture and joint fluid of five patients who underwent valvular surgery. Growth rate and early biofilm production of selected isolates were also compared. <i>Results</i>: By sequencing a total of 58 <i>E. faecalis</i> genomes, we detected a considerable genomic microdiversity, not only among strains from different anatomical origins, but also between isolates from the same studied cardiac valves. Interestingly, deletions of thousands of bases including the well-known virulence factors <i>ebpA/B/C</i>, and <i>srtC</i>, as well as other large prophage sequences containing genes coding for proteins implicated in platelet binding (PlbA and PlbB) were evidenced. The study of mutations helped unveil common patterns in genes related to the cell cycle as well as central metabolism, suggesting an evolutionary convergence in these isolates. As expected, such modifications were associated with a significant impact on the <i>in-vitro</i> phenotypic heterogeneity, growth, and early biofilm production. <i>Conclusion</i>: Genome modifications associated with phenotypic variations may allow bacterial adaptation to both antibiotic and immune selective pressures, and thus promote relapses.
DOI: 10.6084/m9.figshare.13602714
title: Comparative pathogenicity and environmental transmission of recent highly pathogenic avian influenza H5 viruses

description: Strategies to control spread of highly pathogenic avian influenza (HPAI) viruses by wild birds appear limited, hence timely characterization of novel viruses is important to mitigate the risk for the poultry sector and human health. In this study we characterize three recent H5-clade 2.3.4.4 viruses, the H5N8-2014 group A virus and the H5N8-2016 and H5N6-2017 group B viruses. The pathogenicity of the three viruses for chickens, Pekin ducks and Eurasian wigeons was compared. The three viruses were highly pathogenic for chickens, but the two H5N8 viruses caused no to mild clinical symptoms in both duck species. The highest pathogenicity for duck species was observed for the most recent H5N6-2017 virus. For both duck species, virus shedding from the cloaca was higher after infection with group B viruses compared to the H5N8-2014 group A virus. Higher cloacal virus shedding of wild ducks may increase transmission between wild birds and poultry. Environmental transmission of H5N8-2016 virus to chickens was studied, which showed that chickens are efficiently infected by (fecal) contaminated water. These results suggest that pathogenicity of HPAI H5 viruses and virus shedding for ducks is evolving, which may have implications for the risk of introduction of these viruses into the poultry sector.
DOI: 10.6084/m9.figshare.13602714.v1
title: Comparative pathogenicity and environmental transmission of recent highly pathogenic avian influenza H5 viruses

description: Strategies to control spread of highly pathogenic avian influenza (HPAI) viruses by wild birds appear limited, hence timely characterization of novel viruses is important to mitigate the risk for the poultry sector and human health. In this study we characterize three recent H5-clade 2.3.4.4 viruses, the H5N8-2014 group A virus and the H5N8-2016 and H5N6-2017 group B viruses. The pathogenicity of the three viruses for chickens, Pekin ducks and Eurasian wigeons was compared. The three viruses were highly pathogenic for chickens, but the two H5N8 viruses caused no to mild clinical symptoms in both duck species. The highest pathogenicity for duck species was observed for the most recent H5N6-2017 virus. For both duck species, virus shedding from the cloaca was higher after infection with group B viruses compared to the H5N8-2014 group A virus. Higher cloacal virus shedding of wild ducks may increase transmission between wild birds and poultry. Environmental transmission of H5N8-2016 virus to chickens was studied, which showed that chickens are efficiently infected by (fecal) contaminated water. These results suggest that pathogenicity of HPAI H5 viruses and virus shedding for ducks is evolving, which may have implications for the risk of introduction of these viruses into the poultry sector.
DOI: 10.6084/m9.figshare.13602659
title: Blood transcriptomics to characterize key biological pathways and identify biomarkers for predicting mortality in melioidosis

description: Melioidosis is an often lethal tropical disease caused by the Gram-negative bacillus, <i>Burkholderia pseudomallei</i>. The study objective was to characterize transcriptomes in melioidosis patients and identify genes associated with outcome. Whole blood RNA-seq was performed in a discovery set of 29 melioidosis patients and 3 healthy controls. Transcriptomic profiles of patients who did not survive to 28 days were compared with patients who survived and healthy controls, showing 65 genes were significantly up-regulated and 218 were down-regulated in non-survivors compared to survivors. Up-regulated genes were involved in myeloid leukocyte activation, Toll-like receptor cascades and reactive oxygen species metabolic processes. Down-regulated genes were hematopoietic cell lineage, adaptive immune system and lymphocyte activation pathways. RT-qPCR was performed for 28 genes in a validation set of 60 melioidosis patients and 20 healthy controls, confirming differential expression. <i>IL1R2, GAS7, S100A9, IRAK3,</i> and <i>NFKBIA</i> were significantly higher in non-survivors compared with survivors (<i>P</i> &lt; 0.005) and healthy controls (<i>P</i> &lt; 0.0001). The AUROCC of these genes for mortality discrimination ranged from 0.80-0.88. In survivors, expression of <i>IL1R2</i>, <i>S100A9</i> and <i>IRAK3</i> genes decreased significantly over 28 days (<i>P</i> &lt; 0.05). These findings augment our understanding of this severe infection, showing expression levels of specific genes are potential biomarkers to predict melioidosis outcomes.
DOI: 10.6084/m9.figshare.13602659.v1
title: Blood transcriptomics to characterize key biological pathways and identify biomarkers for predicting mortality in melioidosis

description: Melioidosis is an often lethal tropical disease caused by the Gram-negative bacillus, <i>Burkholderia pseudomallei</i>. The study objective was to characterize transcriptomes in melioidosis patients and identify genes associated with outcome. Whole blood RNA-seq was performed in a discovery set of 29 melioidosis patients and 3 healthy controls. Transcriptomic profiles of patients who did not survive to 28 days were compared with patients who survived and healthy controls, showing 65 genes were significantly up-regulated and 218 were down-regulated in non-survivors compared to survivors. Up-regulated genes were involved in myeloid leukocyte activation, Toll-like receptor cascades and reactive oxygen species metabolic processes. Down-regulated genes were hematopoietic cell lineage, adaptive immune system and lymphocyte activation pathways. RT-qPCR was performed for 28 genes in a validation set of 60 melioidosis patients and 20 healthy controls, confirming differential expression. <i>IL1R2, GAS7, S100A9, IRAK3,</i> and <i>NFKBIA</i> were significantly higher in non-survivors compared with survivors (<i>P</i> &lt; 0.005) and healthy controls (<i>P</i> &lt; 0.0001). The AUROCC of these genes for mortality discrimination ranged from 0.80-0.88. In survivors, expression of <i>IL1R2</i>, <i>S100A9</i> and <i>IRAK3</i> genes decreased significantly over 28 days (<i>P</i> &lt; 0.05). These findings augment our understanding of this severe infection, showing expression levels of specific genes are potential biomarkers to predict melioidosis outcomes.
DOI: 10.6084/m9.figshare.16571453
title: Host-dependent editing of SARS-CoV-2 in COVID-19 patients

description: A common trait among RNA viruses is their high capability to acquire genetic variability due to viral and host mechanisms. Next-generation sequencing (NGS) analysis enables the deep study of the viral quasispecies in samples from infected individuals. In this study, the viral quasispecies complexity and single nucleotide polymorphisms of the SARS-CoV-2 <i>spike</i> gene of coronavirus disease 2019 (COVID-19) patients with mild or severe disease were investigated using next-generation sequencing (Illumina platform). SARS-CoV-2 <i>spike</i> variability was higher in patients with long-lasting infection. Most substitutions found were present at frequencies lower than 1%, and had an A → G or T → C pattern, consistent with variants caused by adenosine deaminase acting on RNA-1 (ADAR1). ADAR1 affected a small fraction of replicating genomes, but produced multiple, mainly non-synonymous mutations. ADAR1 editing during replication rather than the RNA-dependent RNA polymerase (nsp12) was the predominant mechanism generating SARS-CoV-2 genetic variability. However, the mutations produced are not fixed in the infected human population, suggesting that ADAR1 may have an antiviral role, whereas nsp12-induced mutations occurring in patients with high viremia and persistent infection are the main source of new SARS-CoV-2 variants.
DOI: 10.6084/m9.figshare.16571453.v1
title: Host-dependent editing of SARS-CoV-2 in COVID-19 patients

description: A common trait among RNA viruses is their high capability to acquire genetic variability due to viral and host mechanisms. Next-generation sequencing (NGS) analysis enables the deep study of the viral quasispecies in samples from infected individuals. In this study, the viral quasispecies complexity and single nucleotide polymorphisms of the SARS-CoV-2 <i>spike</i> gene of coronavirus disease 2019 (COVID-19) patients with mild or severe disease were investigated using next-generation sequencing (Illumina platform). SARS-CoV-2 <i>spike</i> variability was higher in patients with long-lasting infection. Most substitutions found were present at frequencies lower than 1%, and had an A → G or T → C pattern, consistent with variants caused by adenosine deaminase acting on RNA-1 (ADAR1). ADAR1 affected a small fraction of replicating genomes, but produced multiple, mainly non-synonymous mutations. ADAR1 editing during replication rather than the RNA-dependent RNA polymerase (nsp12) was the predominant mechanism generating SARS-CoV-2 genetic variability. However, the mutations produced are not fixed in the infected human population, suggesting that ADAR1 may have an antiviral role, whereas nsp12-induced mutations occurring in patients with high viremia and persistent infection are the main source of new SARS-CoV-2 variants.
DOI: 10.6084/m9.figshare.13602717
title: Hepatic phaeohyphomycosis due to a novel dematiaceous fungus, <i>Pleurostoma hongkongense</i> sp. nov., and importance of antifungal susceptibility testing

description: <i>Pleurostoma</i> species are wood-inhabiting fungi and emerging opportunistic pathogens causing phaeohyphomycosis. In this study, we isolated a dematiaceous fungus, HKU44<sup>T</sup>, from the subhepatic abscess pus and drain fluids of a liver transplant recipient with post-transplant biliary and hepatico-jejunostomy bypass strictures. Histology of the abscess wall biopsy showed abundant fungal hyphae. The patient survived after a second liver transplant and antifungal therapy. On SDA, HKU44<sup>T</sup> grew initially as white powdery colonies which turned beige upon maturation. Hyphae were septate and hyaline. Phialides were monophialidic and laterally located, generally closely associated to a cluster of conidia which were usually reniform. Phylogenetic analyses showed that HKU44<sup>T</sup> is most closely related to, but distinct from, <i>Pleurostoma ootheca</i> and <i>Pleurostoma repens</i>. These suggested that HKU44<sup>T</sup> is a novel <i>Pleurostoma</i> species, for which the name <i>Pleurostoma hongkongense</i> sp. nov. is proposed. Antifungal susceptibility testing showed that <i>Pleurostoma</i> species possessed high MICs/MECs for fluconazole, 5-flucytosine and the echinocandins; whereas they exhibited a high strain-to-strain variability to the susceptibilities to the other triazoles. As for amphotericin B, ∼65% of the <i>Pleurostoma</i> strains had low MICs (≤1 µg/mL). DNA sequencing should be performed to accurately identify fungi with <i>Pleurostoma/Phialophora</i>-like morphologies, so is antifungal susceptibility testing for patients with <i>Pleurostoma</i> infections.
DOI: 10.6084/m9.figshare.13602717.v1
title: Hepatic phaeohyphomycosis due to a novel dematiaceous fungus, <i>Pleurostoma hongkongense</i> sp. nov., and importance of antifungal susceptibility testing

description: <i>Pleurostoma</i> species are wood-inhabiting fungi and emerging opportunistic pathogens causing phaeohyphomycosis. In this study, we isolated a dematiaceous fungus, HKU44<sup>T</sup>, from the subhepatic abscess pus and drain fluids of a liver transplant recipient with post-transplant biliary and hepatico-jejunostomy bypass strictures. Histology of the abscess wall biopsy showed abundant fungal hyphae. The patient survived after a second liver transplant and antifungal therapy. On SDA, HKU44<sup>T</sup> grew initially as white powdery colonies which turned beige upon maturation. Hyphae were septate and hyaline. Phialides were monophialidic and laterally located, generally closely associated to a cluster of conidia which were usually reniform. Phylogenetic analyses showed that HKU44<sup>T</sup> is most closely related to, but distinct from, <i>Pleurostoma ootheca</i> and <i>Pleurostoma repens</i>. These suggested that HKU44<sup>T</sup> is a novel <i>Pleurostoma</i> species, for which the name <i>Pleurostoma hongkongense</i> sp. nov. is proposed. Antifungal susceptibility testing showed that <i>Pleurostoma</i> species possessed high MICs/MECs for fluconazole, 5-flucytosine and the echinocandins; whereas they exhibited a high strain-to-strain variability to the susceptibilities to the other triazoles. As for amphotericin B, ∼65% of the <i>Pleurostoma</i> strains had low MICs (≤1 µg/mL). DNA sequencing should be performed to accurately identify fungi with <i>Pleurostoma/Phialophora</i>-like morphologies, so is antifungal susceptibility testing for patients with <i>Pleurostoma</i> infections.
DOI: 10.6084/m9.figshare.14171259
title: A household case evidences shorter shedding of SARS-CoV-2 in naturally infected cats compared to their human owners

description: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in domestic and wild cats. However, little is known about natural viral infections of domestic cats, although their importance for modelling disease spread, informing strategies for managing positive human-animal relationships and disease prevention. Here, we describe the SARS-CoV-2 infection in a household of two human adults and sibling cats (one male and two females) using real-time RT–PCR, an ELISA test, viral sequencing, and virus isolation. On May 5th, 2020, the cat-owners tested positive for SARS-CoV-2. Two days later, the male cat showed mild respiratory symptoms and tested positive. Four days after the male cat, the two female cats became positive, asymptomatically. Also, one human and one cat showed antibodies against SARS-CoV-2. All cats excreted detectable SARS-CoV-2 RNA for a shorter duration than humans and viral sequences analysis confirmed human-to-cat transmission. We could not determine if cat-to-cat transmission also occurred.
DOI: 10.6084/m9.figshare.14171259.v1
title: A household case evidences shorter shedding of SARS-CoV-2 in naturally infected cats compared to their human owners

description: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been detected in domestic and wild cats. However, little is known about natural viral infections of domestic cats, although their importance for modelling disease spread, informing strategies for managing positive human-animal relationships and disease prevention. Here, we describe the SARS-CoV-2 infection in a household of two human adults and sibling cats (one male and two females) using real-time RT–PCR, an ELISA test, viral sequencing, and virus isolation. On May 5th, 2020, the cat-owners tested positive for SARS-CoV-2. Two days later, the male cat showed mild respiratory symptoms and tested positive. Four days after the male cat, the two female cats became positive, asymptomatically. Also, one human and one cat showed antibodies against SARS-CoV-2. All cats excreted detectable SARS-CoV-2 RNA for a shorter duration than humans and viral sequences analysis confirmed human-to-cat transmission. We could not determine if cat-to-cat transmission also occurred.