cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.9252428
title: Combining sequencing approaches to fully resolve a carbapenemase-encoding megaplasmid in a <i>Pseudomonas shirazica</i> clinical strain

description: Horizontal transfer of plasmids plays a pivotal role in dissemination of antibiotic resistance genes and emergence of multidrug-resistant bacteria. Plasmid sequencing is thus paramount for accurate epidemiological tracking in hospitals and routine surveillance. Combining Nanopore and Illumina sequencing allowed full assembly of a carbapenemase-encoding megaplasmid carried by multidrug-resistant clinical isolate FFUP_PS_41. Average nucleotide identity analyses revealed that FFUP_PS_41 belongs to the recently proposed new species Pseudomonas shirazica, related to the P. putida phylogenetic group. FFUP_PS_41 harbours a 498,516-bp megaplasmid (pJBCL41) with limited similarity to publicly-available plasmids. pJBCL41 contains genes predicted to encode replication, conjugation, partitioning and maintenance functions and heavy metal resistance. The |aacA7|blaVIM-2|aacA4| cassette array (resistance to carbapenems and aminoglycosides) is located within a class 1 integron that is a defective Tn402 derivative. This transposon lies within a 50,273-bp region bound by Tn3-family 38-bp inverted repeats and flanked by 5-bp direct repeats (DR) that composes additional transposon fragments, five insertion sequences and a Tn3-Derived Inverted-Repeat Miniature Element. The hybrid Nanopore/Illumina approach allowed full resolution of a carbapenemase-encoding megaplasmid from P. shirazica. Identification of novel megaplasmids sheds new light on the evolutionary effects of gene transfer and the selective forces driving antibiotic resistance.
DOI: 10.6084/m9.figshare.9252428.v4
title: Combining sequencing approaches to fully resolve a carbapenemase-encoding megaplasmid in a <i>Pseudomonas shirazica</i> clinical strain

description: Horizontal transfer of plasmids plays a pivotal role in dissemination of antibiotic resistance genes and emergence of multidrug-resistant bacteria. Plasmid sequencing is thus paramount for accurate epidemiological tracking in hospitals and routine surveillance. Combining Nanopore and Illumina sequencing allowed full assembly of a carbapenemase-encoding megaplasmid carried by multidrug-resistant clinical isolate FFUP_PS_41. Average nucleotide identity analyses revealed that FFUP_PS_41 belongs to the recently proposed new species Pseudomonas shirazica, related to the P. putida phylogenetic group. FFUP_PS_41 harbours a 498,516-bp megaplasmid (pJBCL41) with limited similarity to publicly-available plasmids. pJBCL41 contains genes predicted to encode replication, conjugation, partitioning and maintenance functions and heavy metal resistance. The |aacA7|blaVIM-2|aacA4| cassette array (resistance to carbapenems and aminoglycosides) is located within a class 1 integron that is a defective Tn402 derivative. This transposon lies within a 50,273-bp region bound by Tn3-family 38-bp inverted repeats and flanked by 5-bp direct repeats (DR) that composes additional transposon fragments, five insertion sequences and a Tn3-Derived Inverted-Repeat Miniature Element. The hybrid Nanopore/Illumina approach allowed full resolution of a carbapenemase-encoding megaplasmid from P. shirazica. Identification of novel megaplasmids sheds new light on the evolutionary effects of gene transfer and the selective forces driving antibiotic resistance.
DOI: 10.6084/m9.figshare.9252428.v3
title: Combining sequencing approaches to fully resolve a carbapenemase-encoding megaplasmid in a <i>Pseudomonas shirazica</i> clinical strain

description: Horizontal transfer of plasmids plays a pivotal role in dissemination of antibiotic resistance genes and emergence of multidrug-resistant bacteria. Plasmid sequencing is thus paramount for accurate epidemiological tracking in hospitals and routine surveillance. Combining Nanopore and Illumina sequencing allowed full assembly of a carbapenemase-encoding megaplasmid carried by multidrug-resistant clinical isolate FFUP_PS_41. Average nucleotide identity analyses revealed that FFUP_PS_41 belongs to the recently proposed new species Pseudomonas shirazica, related to the P. putida phylogenetic group. FFUP_PS_41 harbours a 498,516-bp megaplasmid (pJBCL41) with limited similarity to publicly-available plasmids. pJBCL41 contains genes predicted to encode replication, conjugation, partitioning and maintenance functions and heavy metal resistance. The |aacA7|blaVIM-2|aacA4| cassette array (resistance to carbapenems and aminoglycosides) is located within a class 1 integron that is a defective Tn402 derivative. This transposon lies within a 50,273-bp region bound by Tn3-family 38-bp inverted repeats and flanked by 5-bp direct repeats (DR) that composes additional transposon fragments, five insertion sequences and a Tn3-Derived Inverted-Repeat Miniature Element. The hybrid Nanopore/Illumina approach allowed full resolution of a carbapenemase-encoding megaplasmid from P. shirazica. Identification of novel megaplasmids sheds new light on the evolutionary effects of gene transfer and the selective forces driving antibiotic resistance.
DOI: 10.6084/m9.figshare.8320670
title: Identification of a novel alphavirus related to the encephalitis complexes circulating in southern Brazil

description: In early 2017, an outbreak caused by an unknown and supposedly viral agent in the Marilena region of southern Brazil was investigated. Since the etiological agent causing the outbreak was not identified from human samples, mosquitoes from this region were collected. Three out of 121 mosquito pools collected from the region tested positive for alphavirus in molecular tests. Next generation sequencing results revealed the presence of a novel alphavirus, tentatively named here as Caainguá virus (CAAV). DNA barcoding analyses indicated that different species of <i>Culex</i> are hosts for CAAV. This new virus was basal to the New World encephalitic alphaviruses in a comprehensive and robust phylogenetic approach using complete genomes. Viral particles were observed in the cytosol and inside of intracellular compartments of cells in mosquito-derived cell cultures. Despite being noninfectious in vertebrate derived cell cultures, primary culturing of CAAV in human mononuclear cells suggests monocytes and lymphocytes as CAAV targets. However, the epidemiological link of CAAV on the human outbreak should be further explored.
DOI: 10.6084/m9.figshare.8320670.v3
title: Identification of a novel alphavirus related to the encephalitis complexes circulating in southern Brazil

description: In early 2017, an outbreak caused by an unknown and supposedly viral agent in the Marilena region of southern Brazil was investigated. Since the etiological agent causing the outbreak was not identified from human samples, mosquitoes from this region were collected. Three out of 121 mosquito pools collected from the region tested positive for alphavirus in molecular tests. Next generation sequencing results revealed the presence of a novel alphavirus, tentatively named here as Caainguá virus (CAAV). DNA barcoding analyses indicated that different species of <i>Culex</i> are hosts for CAAV. This new virus was basal to the New World encephalitic alphaviruses in a comprehensive and robust phylogenetic approach using complete genomes. Viral particles were observed in the cytosol and inside of intracellular compartments of cells in mosquito-derived cell cultures. Despite being noninfectious in vertebrate derived cell cultures, primary culturing of CAAV in human mononuclear cells suggests monocytes and lymphocytes as CAAV targets. However, the epidemiological link of CAAV on the human outbreak should be further explored.
DOI: 10.6084/m9.figshare.8320670.v4
title: Identification of a novel alphavirus related to the encephalitis complexes circulating in southern Brazil

description: In early 2017, an outbreak caused by an unknown and supposedly viral agent in the Marilena region of southern Brazil was investigated. Since the etiological agent causing the outbreak was not identified from human samples, mosquitoes from this region were collected. Three out of 121 mosquito pools collected from the region tested positive for alphavirus in molecular tests. Next generation sequencing results revealed the presence of a novel alphavirus, tentatively named here as Caainguá virus (CAAV). DNA barcoding analyses indicated that different species of <i>Culex</i> are hosts for CAAV. This new virus was basal to the New World encephalitic alphaviruses in a comprehensive and robust phylogenetic approach using complete genomes. Viral particles were observed in the cytosol and inside of intracellular compartments of cells in mosquito-derived cell cultures. Despite being noninfectious in vertebrate derived cell cultures, primary culturing of CAAV in human mononuclear cells suggests monocytes and lymphocytes as CAAV targets. However, the epidemiological link of CAAV on the human outbreak should be further explored.
DOI: 10.6084/m9.figshare.7937462.v4
title: Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein

description: The Middle-East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that causes severe and often fatal respiratory disease in humans. Efforts to develop antibody-based therapies have focused on neutralizing antibodies that target the receptor binding domain of the viral spike protein thereby blocking receptor binding. Here, we developed a set of human monoclonal antibodies that target functionally distinct domains of the MERS-CoV spike protein. These antibodies belong to six distinct epitope groups and interfere with the three critical entry functions of the MERS-CoV spike protein: sialic acid binding, receptor binding and membrane fusion. Passive immunization with potently as well as with poorly neutralizing antibodies protected mice from lethal MERS-CoV challenge. Collectively, these antibodies offer new ways to gain humoral protection in humans against the emerging MERS-CoV by targeting different spike protein epitopes and functions.
DOI: 10.6084/m9.figshare.9891728
title: The cytochrome d oxidase complex regulated by fexA is an Achilles' heel in the <i>in vivo</i> survival of <i>Vibrio vulnificus</i>

description: <i>Vibrio vulnificus</i> is a halophilic estuarine bacterium causing severe opportunistic infections. To successfully establish an infection, <i>V. vulnificus</i> must adapt to redox fluctuations in vivo. In the present study, we show that deletion of <i>V. vulnificus</i> fexA gene caused hypersensitivity to acid and reactive oxygen species. The <i>ΔfexA</i> mutant exhibited severe in vivo survival defects. For deeper understanding the role of <i>fexA</i> gene on the successful <i>V. vulnificus</i> infection, we analyzed differentially expressed genes in <i>ΔfexA</i> mutant in comparison with wild type under aerobic, anaerobic or in vivo culture conditions by genome-scale DNA microarray analyses. Twenty-two genes were downregulated in the <i>ΔfexA</i> mutant under all three culture conditions. Among them, <i>cydAB</i> appeared to dominantly contribute to the defective phenotypes of the <i>ΔfexA</i> mutant. The <i>fexA</i> deletion induced compensatory point mutations in the <i>cydAB</i> promoter region over subcultures, suggesting essentiality. Those point mutations (P<sub>cyd</sub>SMs) restored bacterial growth, motility, cytotoxicity ATP production and mouse lethality in the <i>ΔfexA</i> mutant. These results indicate that the <i>cydAB</i> operon, being regulated by <i>FexA</i>, plays a crucial role in <i>V. vulnificus</i> survival under redox-fluctuating in vivo conditions. The FexA-CydAB axis should serve an Achilles heel in the development of therapeutic regimens against <i>V. vulnificus</i> infection.
DOI: 10.6084/m9.figshare.9891728.v3
title: The cytochrome d oxidase complex regulated by fexA is an Achilles' heel in the <i>in vivo</i> survival of <i>Vibrio vulnificus</i>

description: <i>Vibrio vulnificus</i> is a halophilic estuarine bacterium causing severe opportunistic infections. To successfully establish an infection, <i>V. vulnificus</i> must adapt to redox fluctuations in vivo. In the present study, we show that deletion of <i>V. vulnificus</i> fexA gene caused hypersensitivity to acid and reactive oxygen species. The <i>ΔfexA</i> mutant exhibited severe in vivo survival defects. For deeper understanding the role of <i>fexA</i> gene on the successful <i>V. vulnificus</i> infection, we analyzed differentially expressed genes in <i>ΔfexA</i> mutant in comparison with wild type under aerobic, anaerobic or in vivo culture conditions by genome-scale DNA microarray analyses. Twenty-two genes were downregulated in the <i>ΔfexA</i> mutant under all three culture conditions. Among them, <i>cydAB</i> appeared to dominantly contribute to the defective phenotypes of the <i>ΔfexA</i> mutant. The <i>fexA</i> deletion induced compensatory point mutations in the <i>cydAB</i> promoter region over subcultures, suggesting essentiality. Those point mutations (P<sub>cyd</sub>SMs) restored bacterial growth, motility, cytotoxicity ATP production and mouse lethality in the <i>ΔfexA</i> mutant. These results indicate that the <i>cydAB</i> operon, being regulated by <i>FexA</i>, plays a crucial role in <i>V. vulnificus</i> survival under redox-fluctuating in vivo conditions. The FexA-CydAB axis should serve an Achilles heel in the development of therapeutic regimens against <i>V. vulnificus</i> infection.
DOI: 10.6084/m9.figshare.9891728.v4
title: The cytochrome d oxidase complex regulated by fexA is an Achilles' heel in the <i>in vivo</i> survival of <i>Vibrio vulnificus</i>

description: <i>Vibrio vulnificus</i> is a halophilic estuarine bacterium causing severe opportunistic infections. To successfully establish an infection, <i>V. vulnificus</i> must adapt to redox fluctuations in vivo. In the present study, we show that deletion of <i>V. vulnificus</i> fexA gene caused hypersensitivity to acid and reactive oxygen species. The <i>ΔfexA</i> mutant exhibited severe in vivo survival defects. For deeper understanding the role of <i>fexA</i> gene on the successful <i>V. vulnificus</i> infection, we analyzed differentially expressed genes in <i>ΔfexA</i> mutant in comparison with wild type under aerobic, anaerobic or in vivo culture conditions by genome-scale DNA microarray analyses. Twenty-two genes were downregulated in the <i>ΔfexA</i> mutant under all three culture conditions. Among them, <i>cydAB</i> appeared to dominantly contribute to the defective phenotypes of the <i>ΔfexA</i> mutant. The <i>fexA</i> deletion induced compensatory point mutations in the <i>cydAB</i> promoter region over subcultures, suggesting essentiality. Those point mutations (P<sub>cyd</sub>SMs) restored bacterial growth, motility, cytotoxicity ATP production and mouse lethality in the <i>ΔfexA</i> mutant. These results indicate that the <i>cydAB</i> operon, being regulated by <i>FexA</i>, plays a crucial role in <i>V. vulnificus</i> survival under redox-fluctuating in vivo conditions. The FexA-CydAB axis should serve an Achilles heel in the development of therapeutic regimens against <i>V. vulnificus</i> infection.
DOI: 10.6084/m9.figshare.7937462
title: Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein

description: The Middle-East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that causes severe and often fatal respiratory disease in humans. Efforts to develop antibody-based therapies have focused on neutralizing antibodies that target the receptor binding domain of the viral spike protein thereby blocking receptor binding. Here, we developed a set of human monoclonal antibodies that target functionally distinct domains of the MERS-CoV spike protein. These antibodies belong to six distinct epitope groups and interfere with the three critical entry functions of the MERS-CoV spike protein: sialic acid binding, receptor binding and membrane fusion. Passive immunization with potently as well as with poorly neutralizing antibodies protected mice from lethal MERS-CoV challenge. Collectively, these antibodies offer new ways to gain humoral protection in humans against the emerging MERS-CoV by targeting different spike protein epitopes and functions.
DOI: 10.6084/m9.figshare.7937462.v3
title: Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein

description: The Middle-East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus that causes severe and often fatal respiratory disease in humans. Efforts to develop antibody-based therapies have focused on neutralizing antibodies that target the receptor binding domain of the viral spike protein thereby blocking receptor binding. Here, we developed a set of human monoclonal antibodies that target functionally distinct domains of the MERS-CoV spike protein. These antibodies belong to six distinct epitope groups and interfere with the three critical entry functions of the MERS-CoV spike protein: sialic acid binding, receptor binding and membrane fusion. Passive immunization with potently as well as with poorly neutralizing antibodies protected mice from lethal MERS-CoV challenge. Collectively, these antibodies offer new ways to gain humoral protection in humans against the emerging MERS-CoV by targeting different spike protein epitopes and functions.
DOI: 10.6084/m9.figshare.9693056
title: Emergence of mobile tigecycline resistance mechanism in <i>Escherichia coli</i> strains from migratory birds in China

description: Plasmid-mediated antimicrobial resistance has emerged as one of the principal global issues, posing significant threats to public health. Herein, we reported a mobile tigecycline resistance mechanism Tet(X4) on both plasmid and chromosome in <i>Escherichia coli</i> strains from migratory birds in China. Besides tigecycline, these <i>tet</i>(X4)-positive strains also exhibited elevated MICs to the FDA newly approved tetracycline antibiotics, eravacycline (4 µg/ml) and omadacycline (8 µg/ml). Worrisomely, the <i>tet</i>(X4)-carrying plasmids and chromosome also shared high homology with the plasmids from human. Taken together, Tet(X4) represents another emerging antimicrobial threat and collective efforts from different sectors are needed to control its further spread.
DOI: 10.6084/m9.figshare.9693056.v3
title: Emergence of mobile tigecycline resistance mechanism in <i>Escherichia coli</i> strains from migratory birds in China

description: Plasmid-mediated antimicrobial resistance has emerged as one of the principal global issues, posing significant threats to public health. Herein, we reported a mobile tigecycline resistance mechanism Tet(X4) on both plasmid and chromosome in <i>Escherichia coli</i> strains from migratory birds in China. Besides tigecycline, these <i>tet</i>(X4)-positive strains also exhibited elevated MICs to the FDA newly approved tetracycline antibiotics, eravacycline (4 µg/ml) and omadacycline (8 µg/ml). Worrisomely, the <i>tet</i>(X4)-carrying plasmids and chromosome also shared high homology with the plasmids from human. Taken together, Tet(X4) represents another emerging antimicrobial threat and collective efforts from different sectors are needed to control its further spread.
DOI: 10.6084/m9.figshare.9693056.v2
title: Emergence of mobile tigecycline resistance mechanism in <i>Escherichia coli</i> strains from migratory birds in China

description: Plasmid-mediated antimicrobial resistance has emerged as one of the principal global issues, posing significant threats to public health. Herein, we reported a mobile tigecycline resistance mechanism Tet(X4) on both plasmid and chromosome in <i>Escherichia coli</i> strains from migratory birds in China. Besides tigecycline, these <i>tet</i>(X4)-positive strains also exhibited elevated MICs to the FDA newly approved tetracycline antibiotics, eravacycline (4 µg/ml) and omadacycline (8 µg/ml). Worrisomely, the <i>tet</i>(X4)-carrying plasmids and chromosome also shared high homology with the plasmids from human. Taken together, Tet(X4) represents another emerging antimicrobial threat and collective efforts from different sectors are needed to control its further spread.
DOI: 10.6084/m9.figshare.9731051
title: Comprehensive analysis of the lysine acetylome in <i>Aeromonas hydrophila</i> reveals cross-talk between lysine acetylation and succinylation in LuxS

description: Lysine acetylation and succinylation are both prevalent protein post-translational modifications (PTMs) in bacteria species, whereas the effect of the cross-talk between both PTMs on bacterial biological function remains largely unknown. Our previously study found lysine succinylated sites on proteins play important role on metabolic pathways in fish pathogenic <i>Aeromonas hydrophila</i>. A total of 3189 lysine-acetylation sites were further identified on 1013 proteins of this pathogen using LC-MS/MS in this study. Functional examination of these PTMs peptides showed associations with basal biological processes, especially metabolic pathways. Additionally, when comparing the obtained lysine acetylome to a previously obtained lysine succinylome, 1198 sites in a total of 547 proteins were found to be in common and associated with various metabolic pathways. As the autoinducer-2 (AI-2) synthase involved in quorum sensing of bacteria, the site-directed mutagenesis of LuxS at the K165 site was performed and revealed that the cross-talk between lysine acetylation and succinylation exerts an inverse influence on bacterial quorum sensing and on LuxS enzymatic activity. In summary, this study provides an in-depth <i>A. hydrophila</i> lysine acetylome profile and for the first time reveals the role of cross-talk between lysine acetylation and succinylation, and its potential impact on bacterial physiological functions.
DOI: 10.6084/m9.figshare.9731051.v2
title: Comprehensive analysis of the lysine acetylome in <i>Aeromonas hydrophila</i> reveals cross-talk between lysine acetylation and succinylation in LuxS

description: Lysine acetylation and succinylation are both prevalent protein post-translational modifications (PTMs) in bacteria species, whereas the effect of the cross-talk between both PTMs on bacterial biological function remains largely unknown. Our previously study found lysine succinylated sites on proteins play important role on metabolic pathways in fish pathogenic <i>Aeromonas hydrophila</i>. A total of 3189 lysine-acetylation sites were further identified on 1013 proteins of this pathogen using LC-MS/MS in this study. Functional examination of these PTMs peptides showed associations with basal biological processes, especially metabolic pathways. Additionally, when comparing the obtained lysine acetylome to a previously obtained lysine succinylome, 1198 sites in a total of 547 proteins were found to be in common and associated with various metabolic pathways. As the autoinducer-2 (AI-2) synthase involved in quorum sensing of bacteria, the site-directed mutagenesis of LuxS at the K165 site was performed and revealed that the cross-talk between lysine acetylation and succinylation exerts an inverse influence on bacterial quorum sensing and on LuxS enzymatic activity. In summary, this study provides an in-depth <i>A. hydrophila</i> lysine acetylome profile and for the first time reveals the role of cross-talk between lysine acetylation and succinylation, and its potential impact on bacterial physiological functions.