cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.21600485.v1
title: Screening for eukaryotic motifs in <i>Legionella pneumophila</i> reveals Smh1 as bacterial deacetylase of host histones

description: <i>Legionella pneumophila</i> (<i>L.p</i>.) is a bacterial pathogen which is a common causative agent of pneumonia. In humans, it infects alveolar macrophages and transfers hundreds of virulence factors that interfere with cellular signalling pathways and the transcriptomic landscape to sustain its own replication. By this interaction, it has acquired eukaryote-like protein motifs by gene transfer events that partake in the pathogenicity of <i>Legionella</i>. In a computational screening approach for eukaryotic motifs in the transcriptome of <i>Legionella</i>, we identified the <i>L.p</i>. strain Corby protein ABQ55614 as putative histone-deacetylase and named it “suppressing modifier of histones 1” (Smh1). During infection, Smh1 is translocated from the <i>Legionella</i> vacuole into the host cytosol. When expressed in human macrophage THP-1 cells, Smh1 was localized predominantly in the nucleus, leading to broad histone H3 and H4 deacetylation, blunted expression of a large number of genes (<i>e.g</i>. IL-1β and IL-8), and fostered intracellular bacterial replication. <i>L.p</i>. with a Smh1 knockdown grew normally in media but showed a slight growth defect inside the host cell. Furthermore, Smh1 showed a very potent histone deacetylation activity <i>in vitro</i>, <i>e.g</i>. at H3K14, that could be inhibited by targeted mutation of the putative catalytic center inferred by analogy with eukaryotic HDAC8, and with the deacetylase inhibitor trichostatin A. In summary, Smh1 displays functional homology with class I/II type HDACs. We identified Smh1 as a new <i>Legionella</i> virulence factor with a eukaryote-like histone-deacetylase activity that moderates host gene expression and might pave the way for further histone modifications. IMPORTANCE <i>Legionella pneumophila (L.p.)</i> is a prominent bacterial pathogen, which is a common causative agent of pneumonia. In order to survive inside the host cell, the human macrophage, it profoundly interacts with host cell processes to advance its own replication. In this study, we identify a bacterial factor, Smh1, with yet unknown function as a host histone deacetylase. The activity of this factor in the host cell leads to attenuated gene expression and increased intracellular bacterial replication.
DOI: 10.6084/m9.figshare.19646376
title: Hypoxia triggers the outbreak of infectious spleen and kidney necrosis virus disease through viral hypoxia response elements

description: Hypoxia frequently occurs in aquatic environments, especially in aquaculture areas. However, research on the relationship between hypoxic aquatic environments with viral diseases outbreak is limited, and its underlying mechanisms remain elusive. Herein, we demonstrated that hypoxia directly triggers the outbreak of infectious spleen and kidney necrosis virus (ISKNV) disease. Hypoxia or activated hypoxia-inducible factor (HIF) pathway could remarkably increase the levels of viral genomic DNA, titers, and gene expression, indicating that ISKNV can response to hypoxia and HIF pathway. To reveal the mechanism of ISKNV respond to HIF pathway, we identified the viral hypoxia response elements (HREs) in ISKNV genome. Fifteen viral HREs were identified, and four related viral genes responded to the HIF pathway, in which the <i>hre-orf077r</i> promoter remarkably responded to the HIF pathway. The level of <i>orf077r</i> mRNA dramatically increased after the infected cells were treated with dimethyloxalylglycine (DMOG) or the infected cells/fish subjected to hypoxic conditions, and overexpressed <i>orf077r</i> could remarkably increase the ISKNV replication. These finding shows that hypoxic aquatic environments induce the expression of viral genes through the viral HREs to promote ISKNV replication, indicating that viral HREs might be important biomarkers for the evaluation of the sensitivity of aquatic animal viral response to hypoxia stress. Furthermore, the frequencies of viral HREs in 43 species aquatic viral genomes from 16 families were predicted and the results indicate that some aquatic animal viruses, such as <i>Picornavirdea, Dicistronviridae</i>, and <i>Herpesviridae</i>, may have a high risk to outbreak when the aquatic environment encounters hypoxic stress.
DOI: 10.6084/m9.figshare.19646376.v1
title: Hypoxia triggers the outbreak of infectious spleen and kidney necrosis virus disease through viral hypoxia response elements

description: Hypoxia frequently occurs in aquatic environments, especially in aquaculture areas. However, research on the relationship between hypoxic aquatic environments with viral diseases outbreak is limited, and its underlying mechanisms remain elusive. Herein, we demonstrated that hypoxia directly triggers the outbreak of infectious spleen and kidney necrosis virus (ISKNV) disease. Hypoxia or activated hypoxia-inducible factor (HIF) pathway could remarkably increase the levels of viral genomic DNA, titers, and gene expression, indicating that ISKNV can response to hypoxia and HIF pathway. To reveal the mechanism of ISKNV respond to HIF pathway, we identified the viral hypoxia response elements (HREs) in ISKNV genome. Fifteen viral HREs were identified, and four related viral genes responded to the HIF pathway, in which the <i>hre-orf077r</i> promoter remarkably responded to the HIF pathway. The level of <i>orf077r</i> mRNA dramatically increased after the infected cells were treated with dimethyloxalylglycine (DMOG) or the infected cells/fish subjected to hypoxic conditions, and overexpressed <i>orf077r</i> could remarkably increase the ISKNV replication. These finding shows that hypoxic aquatic environments induce the expression of viral genes through the viral HREs to promote ISKNV replication, indicating that viral HREs might be important biomarkers for the evaluation of the sensitivity of aquatic animal viral response to hypoxia stress. Furthermore, the frequencies of viral HREs in 43 species aquatic viral genomes from 16 families were predicted and the results indicate that some aquatic animal viruses, such as <i>Picornavirdea, Dicistronviridae</i>, and <i>Herpesviridae</i>, may have a high risk to outbreak when the aquatic environment encounters hypoxic stress.
DOI: 10.6084/m9.figshare.19794189
title: Repertoires of SARS-CoV-2 epitopes targeted by antibodies vary according to severity of COVID-19

description: Antibodies to SARS-CoV-2 are central to recovery and immunity from COVID-19. However, the relationship between disease severity and the repertoire of antibodies against specific SARS-CoV-2 epitopes an individual develops following exposure remains incompletely understood. Here, we studied seroprevalence of antibodies to specific SARS-CoV-2 and other betacoronavirus antigens in a well-annotated, community sample of convalescent and never-infected individuals obtained in August 2020. One hundred and twenty-four participants were classified into five groups: previously exposed but without evidence of infection, having no known exposure or evidence of infection, seroconverted without symptoms, previously diagnosed with symptomatic COVID-19, and recovered after hospitalization with COVID-19. Prevalence of IgGs specific to the following antigens was compared between the five groups: recombinant SARS-CoV-2 and betacoronavirus spike and nucleocapsid protein domains, peptides from a tiled array of 22-mers corresponding to the entire spike and nucleocapsid proteins, and peptides corresponding to predicted immunogenic regions from other proteins of SARS-CoV-2. Antibody abundance generally correlated positively with severity of prior illness. A number of specific immunogenic peptides and some that may be associated with milder illness or protection from symptomatic infection were identified. No convincing association was observed between antibodies to Receptor Binding Domain(s) (RBDs) of less pathogenic betacoronaviruses HKU1 or OC43 and COVID-19 severity. However, apparent cross-reaction with SARS-CoV RBD was evident and some predominantly asymptomatic individuals had antibodies to both MERS-CoV and SARS-CoV RBDs. Findings from this pilot study may inform development of diagnostics, vaccines, and therapeutic antibodies, and provide insight into viral pathogenic mechanisms.
DOI: 10.6084/m9.figshare.19794189.v1
title: Repertoires of SARS-CoV-2 epitopes targeted by antibodies vary according to severity of COVID-19

description: Antibodies to SARS-CoV-2 are central to recovery and immunity from COVID-19. However, the relationship between disease severity and the repertoire of antibodies against specific SARS-CoV-2 epitopes an individual develops following exposure remains incompletely understood. Here, we studied seroprevalence of antibodies to specific SARS-CoV-2 and other betacoronavirus antigens in a well-annotated, community sample of convalescent and never-infected individuals obtained in August 2020. One hundred and twenty-four participants were classified into five groups: previously exposed but without evidence of infection, having no known exposure or evidence of infection, seroconverted without symptoms, previously diagnosed with symptomatic COVID-19, and recovered after hospitalization with COVID-19. Prevalence of IgGs specific to the following antigens was compared between the five groups: recombinant SARS-CoV-2 and betacoronavirus spike and nucleocapsid protein domains, peptides from a tiled array of 22-mers corresponding to the entire spike and nucleocapsid proteins, and peptides corresponding to predicted immunogenic regions from other proteins of SARS-CoV-2. Antibody abundance generally correlated positively with severity of prior illness. A number of specific immunogenic peptides and some that may be associated with milder illness or protection from symptomatic infection were identified. No convincing association was observed between antibodies to Receptor Binding Domain(s) (RBDs) of less pathogenic betacoronaviruses HKU1 or OC43 and COVID-19 severity. However, apparent cross-reaction with SARS-CoV RBD was evident and some predominantly asymptomatic individuals had antibodies to both MERS-CoV and SARS-CoV RBDs. Findings from this pilot study may inform development of diagnostics, vaccines, and therapeutic antibodies, and provide insight into viral pathogenic mechanisms.
DOI: 10.6084/m9.figshare.21295520
title: <i>Aeromonas salmonicida</i> binds α2-6 linked sialic acid, which is absent among the glycosphingolipid repertoires from skin, gill, stomach, pyloric caecum, and intestine

description: Carbohydrates can both protect against infection and act as targets promoting infection. Mucins are major components of the slimy mucus layer covering the fish epithelia. Mucins can act as decoys for intimate pathogen interaction with the host afforded by binding to glycosphingolipids in the host cell membrane. We isolated and characterized glycosphingolipids from Atlantic salmon skin, gill, stomach, pyloric caeca, and intestine. We characterized the glycosphingolipids using liquid chromatography – mass spectrometry and tandem mass spectrometry and the glycan repertoire was compared with the glycan repertoire of mucins from the same epithelia. We also investigated <i>Aeromonas salmonicida</i> binding using chromatogram and microtiter well based binding assays. We identified 29 glycosphingolipids. All detected acid glycans were of the ganglio-series (unless shorter) and showed a high degree of polysialylation. The non-acid glycans were mostly composed of the neolacto, globo, and ganglio core structures. The glycosphingolipid repertoire differed between epithelia and the proportion of the terminal moieties of the glycosphingolipids did not reflect the terminal moieties on the mucins from the same epithelia. <i>A. salmonicida</i> did not bind the Atlantic salmon glycosphingolipids. Instead, we identified that <i>A. salmonicida</i> binding to sialic acid occurred to α2–6 Neu5Ac but not to α2–3 Neu5Ac. α2–6 Neu5Ac was present on mucins whereas mainly α2–3 Neu5Ac was found on the glycosphingolipids, explaining the difference in <i>A. salmonicida</i> binding ability between these host glycoconjugates. <i>A. salmonicida´s</i> ability to bind to Atlantic salmon mucins, but not the glycosphingolipids, is likely part of the host defence against this pathogen.
DOI: 10.6084/m9.figshare.20001335
title: Coinfection in the host can result in functional complementation between live vaccines and virulent virus

description: One of the greatest achievements of the last century is the development of vaccines against viral diseases. Vaccines are essential for battling infectious diseases and many different formulations are available, including live attenuated vaccines. However, the use of live attenuated vaccines has the potential for adverse effects, including reversion of pathogenicity, recombination, and functional complementation in the host. Marek’s disease is a serious disease in poultry controlled by live attenuated vaccines that has resulted in increased virulence over the decades. Recombination between circulating field viruses or vaccines is a proposed mechanism for the increase in virulence, however, complementation between vaccines and field strains has not been demonstrated in chickens. Here, we describe functional complementation of vaccines with virulent virus to functionally complement transmission and spread in the host. Using the natural virus-host model of Marek’s disease in chickens, our results show dual infection of target cells in chickens with vaccine and virulent virus providing the opportunity for recombination or complementation to transpire. Interestingly, our controlled results showed no evidence of recombination between vaccine and virulent virus, but functional complementation occurred in two independent experiments providing proof for complementation during natural infection in vaccinated individuals. These results suggest complementation as a potential mechanism for vaccine-mediated viral evolution and the potential for complementation should be taken into consideration when developing novel vaccines.
DOI: 10.6084/m9.figshare.20001335.v1
title: Coinfection in the host can result in functional complementation between live vaccines and virulent virus

description: One of the greatest achievements of the last century is the development of vaccines against viral diseases. Vaccines are essential for battling infectious diseases and many different formulations are available, including live attenuated vaccines. However, the use of live attenuated vaccines has the potential for adverse effects, including reversion of pathogenicity, recombination, and functional complementation in the host. Marek’s disease is a serious disease in poultry controlled by live attenuated vaccines that has resulted in increased virulence over the decades. Recombination between circulating field viruses or vaccines is a proposed mechanism for the increase in virulence, however, complementation between vaccines and field strains has not been demonstrated in chickens. Here, we describe functional complementation of vaccines with virulent virus to functionally complement transmission and spread in the host. Using the natural virus-host model of Marek’s disease in chickens, our results show dual infection of target cells in chickens with vaccine and virulent virus providing the opportunity for recombination or complementation to transpire. Interestingly, our controlled results showed no evidence of recombination between vaccine and virulent virus, but functional complementation occurred in two independent experiments providing proof for complementation during natural infection in vaccinated individuals. These results suggest complementation as a potential mechanism for vaccine-mediated viral evolution and the potential for complementation should be taken into consideration when developing novel vaccines.
DOI: 10.6084/m9.figshare.19367131
title: Presence and function of Hbl B’, the fourth protein component encoded by the <i>hbl</i> operon in <i>Bacillus cereus</i>

description: The genes <i>hblC</i>, <i>hblD</i> and <i>hblA</i> encode the components Hbl L2, L1 and B of the pore forming enterotoxin haemolysin BL of <i>Bacillus cereus</i>. Two variants of the operon existand the more common one additionally contains <i>hblB</i> downstream of <i>hblCDA</i>. Up to now, it was completely unclear whether the corresponding protein, Hbl B’, is widely expressed among <i>B. cereus</i> strains and if it has a distinct function. In the present study, it was shown that the <i>hblB</i> gene is indeed expressed and the Hbl B’ protein is secreted by nearly all analysed <i>B. cereus</i> strains. For the latter, a detection system was developed based on monoclonal antibody 11A5. Further, a distinct reduction of cytotoxic and haemolytic activity was observed when recombinant (r)Hbl B’ was applied simultaneously with L2, L1 and B. This effect was due to direct interaction of rHbl B’ with L1. <sub>D</sub><sup>−6</sup><i>B. cereus</i>Altogether, we present the first simple tool for the detection of Hbl B’ in <i>B. cereus</i> culture supernatants. Moreover, an important regulatory function of Hbl B’ in the mechanism of Hbl was determined, which is best described as an additional control of complex formation, balancing the amounts of Hbl B-L1 complexes and the corresponding free subunits.
DOI: 10.6084/m9.figshare.19722339
title: An iron-chelating sulfonamide identified from <i>Drosophila</i>-based screening for antipathogenic discovery

description: We exploited bacterial infection assays using the fruit fly <i>Drosophila melanogaster</i> to identify anti-infective compounds that abrogate the pathological consequences in the infected hosts. Here, we demonstrated that a pyridine-3-<i>N</i>-sulfonylpiperidine derivative (<b>4a</b>) protects <i>Drosophila</i> from the acute infections caused by bacterial pathogens including <i>Pseudomonas aeruginosa</i>. <b>4a</b> did not inhibit the growth of <i>P. aeruginosa</i> in vitro, but inhibited the production of secreted toxins such as pyocyanin and hydrogen cyanide, while enhancing the production of pyoverdine and pyochelin, indicative of iron deprivation. Based on its catechol moiety, <b>4a</b> displayed iron-chelating activity in vitro toward both iron (II) and iron (III), more efficiently than the approved iron-chelating drugs such as deferoxamine and deferiprone, concomitant with more potent antibacterial efficacy in <i>Drosophila</i> infections and unique transcriptome profile. Taken together, these results delineate a <i>Drosophila</i>–based strategy to screen for antipathogenic compounds, which interfere with iron uptake crucial for bacterial virulence and survival in host tissues.
DOI: 10.6084/m9.figshare.19722339.v1
title: An iron-chelating sulfonamide identified from <i>Drosophila</i>-based screening for antipathogenic discovery

description: We exploited bacterial infection assays using the fruit fly <i>Drosophila melanogaster</i> to identify anti-infective compounds that abrogate the pathological consequences in the infected hosts. Here, we demonstrated that a pyridine-3-<i>N</i>-sulfonylpiperidine derivative (<b>4a</b>) protects <i>Drosophila</i> from the acute infections caused by bacterial pathogens including <i>Pseudomonas aeruginosa</i>. <b>4a</b> did not inhibit the growth of <i>P. aeruginosa</i> in vitro, but inhibited the production of secreted toxins such as pyocyanin and hydrogen cyanide, while enhancing the production of pyoverdine and pyochelin, indicative of iron deprivation. Based on its catechol moiety, <b>4a</b> displayed iron-chelating activity in vitro toward both iron (II) and iron (III), more efficiently than the approved iron-chelating drugs such as deferoxamine and deferiprone, concomitant with more potent antibacterial efficacy in <i>Drosophila</i> infections and unique transcriptome profile. Taken together, these results delineate a <i>Drosophila</i>–based strategy to screen for antipathogenic compounds, which interfere with iron uptake crucial for bacterial virulence and survival in host tissues.
DOI: 10.6084/m9.figshare.21201740
title: Comparative transcriptome combined with morphophysiological analyses revealed the molecular mechanism underlying <i>Tetrahymena thermophila</i> predation-induced antiphage defense in <i>Aeromonas hydrophila</i>

description: Protozoan predation has been demonstrated to be a strong driving force for bacterial defence strategies in the environment. Our previous study demonstrated that <i>Aeromonas hydrophila</i> NJ-35, which evolved small-colony variants (SCVs), displayed various adaptive traits in response to <i>Tetrahymena thermophila</i> predation, such as enhanced phage resistance. However, the evolutionary mechanisms are largely unknown. In this study, we performed a genome- and transcriptome-wide analysis of the SCV1, representing one strain of the SCVs, for identification of the genes of mutation and altered expression underlying this phage resistance phenotype. Our study demonstrated that phage resistance caused by <i>T. thermophila</i> predation was due to the downregulation of a flagellar biosynthesis regulator, <i>flhF</i>, in SCV1. Interestingly, we confirmed that phage resistance in SCV1 was not straightforwardly attributable to the absence of flagella but to FlhF-mediated secretion of extracellular protein that hinders phage adsorption. This finding improves our understanding of the mechanisms by which <i>A. hydrophila</i> lowers the susceptibility to phage infection under predation pressure, and highlights an important contribution of bacterium–protozoan interactions in driving the adaptive evolution of pathogens in complex environments.
DOI: 10.6084/m9.figshare.21201740.v1
title: Comparative transcriptome combined with morphophysiological analyses revealed the molecular mechanism underlying <i>Tetrahymena thermophila</i> predation-induced antiphage defense in <i>Aeromonas hydrophila</i>

description: Protozoan predation has been demonstrated to be a strong driving force for bacterial defence strategies in the environment. Our previous study demonstrated that <i>Aeromonas hydrophila</i> NJ-35, which evolved small-colony variants (SCVs), displayed various adaptive traits in response to <i>Tetrahymena thermophila</i> predation, such as enhanced phage resistance. However, the evolutionary mechanisms are largely unknown. In this study, we performed a genome- and transcriptome-wide analysis of the SCV1, representing one strain of the SCVs, for identification of the genes of mutation and altered expression underlying this phage resistance phenotype. Our study demonstrated that phage resistance caused by <i>T. thermophila</i> predation was due to the downregulation of a flagellar biosynthesis regulator, <i>flhF</i>, in SCV1. Interestingly, we confirmed that phage resistance in SCV1 was not straightforwardly attributable to the absence of flagella but to FlhF-mediated secretion of extracellular protein that hinders phage adsorption. This finding improves our understanding of the mechanisms by which <i>A. hydrophila</i> lowers the susceptibility to phage infection under predation pressure, and highlights an important contribution of bacterium–protozoan interactions in driving the adaptive evolution of pathogens in complex environments.