cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.13686190
title: Deletion of Polyamine Transport Protein PotD Exacerbates Virulence in Glaesserella (Haemophilus) parasuis in the Form of Non-biofilm-generated Bacteria in a Murine Acute Infection Model

description: Polyamines are small, polycationic molecules with a hydrocarbon backbone and multiple amino groups required for optimal cell growth. The <i>potD</i> gene, belonging to the ABC (ATP-binding cassette) transport system <i>potABCD</i>, encodes the bacterial substrate-binding subunit of the polyamine transport system, playing a pivotal role in bacterial metabolism and growth. The swine pathogen <i>Glaesserella parasuis</i> possesses an intact <i>pot</i> operon, and the studies presented here mainly examined the involvement of PotD in <i>Glaesserella</i> pathogenesis. A <i>potD</i>-deficient mutant was constructed using a virulent <i>G. parasuis</i> strain SC1401 by natural transformation; immuno-electron microscopy was used to identify the subcellular location of native PotD protein; an electron microscope was adopted to inspect biofilm and bacterial morphology; immunofluorescence technique was employed to study cellular adhesion, the levels of inflammation and apoptosis. The TSA++-pre-cultured mutant strain showed a significantly reduced adhesion capacity to PK-15 and MLE-12 cells. Likewise, we also found attenuation in virulence using murine models focusing on the clinical sign, H&E, and IFA for inflammation and apoptosis. However, when the mutant was grown in TSB++, virulence recovered to normal levels, along with a high level of radical oxygen species formation in the host. The expression of PotD could actively stimulate the production of ROS in Raw 264.7. Our data suggested that PotD from <i>G. parasuis</i> has a high binding potential to polyamine, and is essential for the full bacterial virulence within mouse models. However, the virulence of the <i>potD</i> mutant is highly dependent on its TSA++ culture conditions rather than on biofilm-formation.
DOI: 10.6084/m9.figshare.14617748
title: A phage protein-derived antipathogenic peptide that targets type IV pilus assembly

description: Phage-inspired antibacterial discovery is a new approach that recruits phages in search for antibacterials with new molecular targets, in that phages are the biological entities well adapted to hijack host bacterial physiology in favor of their own thrive. We previously observed that phage-mediated twitching motility inhibition was effective to control the acute infections caused by <i>Pseudomonas aeruginosa</i> and that the motility inhibition was attributed to the delocalization of PilB, the type IV pilus (TFP) assembly ATPase by binding of the 136-amino acid (aa) phage protein, Tip. Here, we created a series of truncated and point-mutant Tip proteins to identify the critical residues in the Tip bioactivity: N-terminal 80-aa residues were dispensable for the Tip activity; we identified that Asp82, Leu84, and Arg85 are crucial in the Tip function. Furthermore, a synthetic 15-aa peptide (P1) that corresponds to Leu73 to Ala87 is shown to suffice for PilB delocalization, twitching inhibition, and virulence attenuation upon exogenous administration. The transgenic flies expressing the 15-aa peptide were resistant to <i>P. aeruginosa</i> infections as well. Taken together, this proof-of-concept study reveals a new antipathogenic peptide hit targeting bacterial motility and provides an insight into antibacterial discovery targeting TFP assembly.
DOI: 10.6084/m9.figshare.13686190.v1
title: Deletion of Polyamine Transport Protein PotD Exacerbates Virulence in Glaesserella (Haemophilus) parasuis in the Form of Non-biofilm-generated Bacteria in a Murine Acute Infection Model

description: Polyamines are small, polycationic molecules with a hydrocarbon backbone and multiple amino groups required for optimal cell growth. The <i>potD</i> gene, belonging to the ABC (ATP-binding cassette) transport system <i>potABCD</i>, encodes the bacterial substrate-binding subunit of the polyamine transport system, playing a pivotal role in bacterial metabolism and growth. The swine pathogen <i>Glaesserella parasuis</i> possesses an intact <i>pot</i> operon, and the studies presented here mainly examined the involvement of PotD in <i>Glaesserella</i> pathogenesis. A <i>potD</i>-deficient mutant was constructed using a virulent <i>G. parasuis</i> strain SC1401 by natural transformation; immuno-electron microscopy was used to identify the subcellular location of native PotD protein; an electron microscope was adopted to inspect biofilm and bacterial morphology; immunofluorescence technique was employed to study cellular adhesion, the levels of inflammation and apoptosis. The TSA++-pre-cultured mutant strain showed a significantly reduced adhesion capacity to PK-15 and MLE-12 cells. Likewise, we also found attenuation in virulence using murine models focusing on the clinical sign, H&E, and IFA for inflammation and apoptosis. However, when the mutant was grown in TSB++, virulence recovered to normal levels, along with a high level of radical oxygen species formation in the host. The expression of PotD could actively stimulate the production of ROS in Raw 264.7. Our data suggested that PotD from <i>G. parasuis</i> has a high binding potential to polyamine, and is essential for the full bacterial virulence within mouse models. However, the virulence of the <i>potD</i> mutant is highly dependent on its TSA++ culture conditions rather than on biofilm-formation.
DOI: 10.6084/m9.figshare.15111819.v1
title: A novel transcription factor UvCGBP1 regulates development and virulence of rice false smut fungus <i>Ustilaginoidea virens</i>

description: <i>Ustilaginoidea virens</i>, causing rice false smut (RFS) is an economically important ascomycetous fungal pathogen distributed in rice-growing regions worldwide. Here, we identified a novel transcription factor UvCGBP1 (Cutinase G-box binding protein) from this fungus, which is unique to ascomycetes. Deletion of <i>UvCGBP1</i> affected development and virulence of <i>U. virens</i>. A total of 865 downstream target genes of UvCGBP1 was identified using ChIP-seq and the most significant KEGG enriched functional pathway was the MAPK signaling pathway. Approximately 36% of target genes contain the AGGGG (G-box) motif in their promoter. Among the targets, deletion of <i>UvCGBP1</i> affected transcriptional and translational levels of <i>UvPmk1</i> and <i>UvSlt2</i>, both of which were important in virulence. ChIP-qPCR, yeast one-hybrid and EMSA confirmed that UvCGBP1 can bind the promoter of <i>UvPmk1</i> or <i>UvSlt2</i>. Overexpression of <i>UvPmk1</i> in the <i>∆UvCGBP1-33</i> mutant restored partially its virulence and hyphae growth, indicating that UvCGBP1 could function via the MAPK pathway to regulate fungal virulence. Taken together, this study uncovered a novel regulatory mechanism of fungal virulence linking the MAPK pathway mediated by a G-box binding transcription factor, UvCGBP1.
DOI: 10.6084/m9.figshare.16653160.v1
title: Genetic diversification of persistent <i>Mycobacterium abscessus</i> within cystic fibrosis patients

description: <i>Mycobacterium</i> (<i>M</i>.) <i>abscessus</i> infections in Cystic Fibrosis (CF) patients cause a deterioration of lung function. Treatment of these multidrug-resistant pathogens is associated with severe side-effects, while frequently unsuccessful. Insight on <i>M. abscessus</i> genomic evolvement during chronic lung infection would be beneficial for improving treatment strategies. A longitudinal study enrolling 42 CF patients was performed at a CF center in Berlin, Germany, to elaborate phylogeny and genomic diversification of in-patient <i>M. abscessus</i>. Eleven of the 42 CF patients were infected with <i>M. abscessus</i>. Five of these 11 patients were infected with global human-transmissible <i>M. abscessus</i> cluster strains. Phylogenetic analysis of 88 genomes from isolates of the 11 patients excluded occurrence of <i>M. abscessus</i> transmission among members of the study group. Genome sequencing and variant analysis of 30 isolates from 11 serial respiratory samples collected over 4.5 years from a chronically infected patient demonstrated accumulation of gene mutations. In total, 53 genes exhibiting non-synonymous variations were identified. Enrichment analysis emphasized genes involved in synthesis of glycopeptidolipids, genes from the <i>embABC</i> (arabinosyltransferase) operon, <i>betA</i> (glucose-methanol-choline oxidoreductase) and <i>cho</i>D (cholesterol oxidase). Genetic diversity evolved in a variety of virulence- and resistance-associated genes. The strategy of <i>M. abscessus</i> populations in chronic lung infection is not clonal expansion of dominant variants, but to sustain simultaneously a wide range of genetic variants facilitating adaptation of the population to changing living conditions in the lung. Genomic diversification during chronic infection requires increased attention when new control strategies against <i>M. abscessus</i> infections are explored.
DOI: 10.6084/m9.figshare.16577823
title: Host-pathogen interactions of clinical <i>S. aureus</i> isolates to induce infective endocarditis

description: To evaluate potential pathomechanisms in the induction of infective endocarditis (IE), 34 <i>Staphylococcus aureus</i> (<i>S. aureus</i>) isolates, collected from patients with <i>S. aureus</i> endocarditis and from healthy individuals were investigated both <i>in vitro</i> and <i>in vivo. S. aureus</i> isolates were tested <i>in vitro</i> for their cytotoxicity, invasion and the association with platelets. Virulence factor expression profiles and cellular response were additionally investigated and tested for correlation with the ability of <i>S. aureus</i> to induce vegetations on the aortic valves <i>in vivo</i>. In an animal model of IE valvular conspicuity was assessed by <i>in vivo</i> magnetic resonance imaging at 9.4 T, histology and enrichment gene expression analysis. All <i>S. aureus</i> isolates tested <i>in vivo</i> caused a reliable infection and inflammation of the aortic valves, but could not be differentiated and categorized according to the measured <i>in vitro</i> virulence profiles and cytotoxicity. Results from <i>in vitro</i> assays did not correlate with the severity of IE. However, the isolates differed substantially in the activation and inhibition of pathways connected to the extracellular matrix and inflammatory response. Thus, comprehensive approaches of host-pathogen interactions and corresponding immune pathways are needed for the evaluation of the pathogenic capacity of bacteria. An improved understanding of the interaction between virulence factors and immune response in <i>S. aureus</i> infective endocarditis would offer novel possibilities for the development of therapeutic strategies and specific diagnostic imaging markers.
DOI: 10.6084/m9.figshare.16577823.v3
title: Host-pathogen interactions of clinical <i>S. aureus</i> isolates to induce infective endocarditis

description: To evaluate potential pathomechanisms in the induction of infective endocarditis (IE), 34 <i>Staphylococcus aureus</i> (<i>S. aureus</i>) isolates, collected from patients with <i>S. aureus</i> endocarditis and from healthy individuals were investigated both <i>in vitro</i> and <i>in vivo. S. aureus</i> isolates were tested <i>in vitro</i> for their cytotoxicity, invasion and the association with platelets. Virulence factor expression profiles and cellular response were additionally investigated and tested for correlation with the ability of <i>S. aureus</i> to induce vegetations on the aortic valves <i>in vivo</i>. In an animal model of IE valvular conspicuity was assessed by <i>in vivo</i> magnetic resonance imaging at 9.4 T, histology and enrichment gene expression analysis. All <i>S. aureus</i> isolates tested <i>in vivo</i> caused a reliable infection and inflammation of the aortic valves, but could not be differentiated and categorized according to the measured <i>in vitro</i> virulence profiles and cytotoxicity. Results from <i>in vitro</i> assays did not correlate with the severity of IE. However, the isolates differed substantially in the activation and inhibition of pathways connected to the extracellular matrix and inflammatory response. Thus, comprehensive approaches of host-pathogen interactions and corresponding immune pathways are needed for the evaluation of the pathogenic capacity of bacteria. An improved understanding of the interaction between virulence factors and immune response in <i>S. aureus</i> infective endocarditis would offer novel possibilities for the development of therapeutic strategies and specific diagnostic imaging markers.
DOI: 10.6084/m9.figshare.17294157
title: The aggregate-forming pili (AFP) mediates the aggregative adherence of a hybrid-pathogenic <i>Escherichia coli</i> (UPEC/EAEC) isolated from a urinary tract infection

description: Enteroaggregative <i>Escherichia coli</i> (EAEC) comprises an important diarrheagenic pathotype, while uropathogenic <i>E. coli</i> (UPEC) is the most important agent of urinary tract infection (UTI). Recently, EAEC virulence factors have been detected in <i>E. coli</i> strains causing UTI, showing the importance of these hybrid-pathogenic strains. Previously, we detected an <i>E. coli</i> strain isolated from UTI (UPEC-46) presenting characteristics of EAEC, <i>e.g</i>., the aggregative adherence (AA) pattern and EAEC-associated genes (<i>aatA, aap</i>, and <i>pet</i>). In this current study, we analyzed the whole genomic sequence of UPEC-46 and characterized some phenotypic traits. The AA phenotype was observed in cell lineages of urinary and intestinal origin. The production of curli, cellulose, bacteriocins, and Pet toxin was detected. Additionally, UPEC-46 was not capable of forming biofilm using different culture media and human urine. The genome sequence analysis showed that this strain belongs to serotype O166:H12, ST10, and phylogroup A, harbors the <i>tet, aadA</i>, and <i>dfrA</i>/<i>sul</i> resistance genes, and is phylogenetically more related to EAEC strains isolated from human feces. UPEC-46 harbors three plasmids. Plasmid p46-1 (~135 kb) carries some EAEC marker genes and those encoding the aggregate-forming pili (AFP) and its regulator (<i>afpR</i>). A mutation in <i>afpA</i> (encoding the AFP major pilin) led to the loss of pilin production and assembly, and notably, a strongly reduced adhesion to epithelial cells. In summary, the genetic background and phenotypic traits analyzed suggest that UPEC-46 is a hybrid strain (UPEC/EAEC) and highlights the importance of AFP adhesin in the adherence to colorectal and bladder cell lines.
DOI: 10.6084/m9.figshare.16577823.v2
title: Host-pathogen interactions of clinical <i>S. aureus</i> isolates to induce infective endocarditis

description: To evaluate potential pathomechanisms in the induction of infective endocarditis (IE), 34 <i>Staphylococcus aureus</i> (<i>S. aureus</i>) isolates, collected from patients with <i>S. aureus</i> endocarditis and from healthy individuals were investigated both <i>in vitro</i> and <i>in vivo. S. aureus</i> isolates were tested <i>in vitro</i> for their cytotoxicity, invasion and the association with platelets. Virulence factor expression profiles and cellular response were additionally investigated and tested for correlation with the ability of <i>S. aureus</i> to induce vegetations on the aortic valves <i>in vivo</i>. In an animal model of IE valvular conspicuity was assessed by <i>in vivo</i> magnetic resonance imaging at 9.4 T, histology and enrichment gene expression analysis. All <i>S. aureus</i> isolates tested <i>in vivo</i> caused a reliable infection and inflammation of the aortic valves, but could not be differentiated and categorized according to the measured <i>in vitro</i> virulence profiles and cytotoxicity. Results from <i>in vitro</i> assays did not correlate with the severity of IE. However, the isolates differed substantially in the activation and inhibition of pathways connected to the extracellular matrix and inflammatory response. Thus, comprehensive approaches of host-pathogen interactions and corresponding immune pathways are needed for the evaluation of the pathogenic capacity of bacteria. An improved understanding of the interaction between virulence factors and immune response in <i>S. aureus</i> infective endocarditis would offer novel possibilities for the development of therapeutic strategies and specific diagnostic imaging markers.
DOI: 10.6084/m9.figshare.16834796
title: Identification of <i>Streptococcus suis</i> putative zoonotic virulence factors: A systematic review and genomic meta-analysis

description: <i>Streptococcus suis</i> is an emerging zoonotic pathogen. Over 100 putative virulence factors have been described, but it is unclear to what extent these virulence factors could contribute to zoonotic potential of <i>S. suis</i>. We identified all <i>S. suis</i> virulence factors studied in experimental models of human origin in a systematic review and assessed their contribution to zoonotic potential in a subsequent genomic meta-analysis. PubMed and Scopus were searched for English-language articles that studied <i>S. suis</i> virulence published until 31 March 2021. Articles that analyzed a virulence factor by knockout mutation, purified protein, and/or recombinant protein in a model of human origin, were included. Data on virulence factor, strain characteristics, used human models and experimental outcomes were extracted. All publicly available <i>S. suis</i> genomes with available metadata on host, disease status and country of origin, were included in a genomic meta-analysis. We calculated the ratio of the prevalence of each virulence factor in human and pig isolates. We included 130 articles and 1703 <i>S. suis</i> genomes in the analysis. We identified 53 putative virulence factors that were encoded by genes which are part of the <i>S. suis</i> core genome and 26 factors that were at least twice as prevalent in human isolates as in pig isolates. Hhly3 and NisK/R were particularly enriched in human isolates, after stratification by genetic lineage and country of isolation. This systematic review and genomic meta-analysis have identified virulence factors that are likely to contribute to the zoonotic potential of <i>S. suis</i>.
DOI: 10.6084/m9.figshare.16834796.v1
title: Identification of <i>Streptococcus suis</i> putative zoonotic virulence factors: a systematic review and genomic meta-analysis

description: <i>Streptococcus suis</i> is an emerging zoonotic pathogen. Over 100 putative virulence factors have been described, but it is unclear to what extent these virulence factors could contribute to zoonotic potential of <i>S. suis</i>. We identified all <i>S. suis</i> virulence factors studied in experimental models of human origin in a systematic review and assessed their contribution to zoonotic potential in a subsequent genomic meta-analysis. PubMed and Scopus were searched for English-language articles that studied <i>S. suis</i> virulence published until March 31, 2021. Articles that analyzed a virulence factor by knockout mutation, purified protein, and/or recombinant protein in a model of human origin, were included. Data on virulence factor, strain characteristics, used human models and experimental outcomes were extracted. All publicly available <i>S. suis</i> genomes with available metadata on host, disease status and country of origin, were included in a genomic meta-analysis. We calculated the ratio of the prevalence of each virulence factor in human and pig isolates. We included 130 articles and 1703 <i>S. suis</i> genomes in the analysis. We identified 53 putative virulence factors that were encoded by genes which are part of the <i>S. suis</i> core genome and 26 factors that were at least twice as prevalent in human isolates as in pig isolates. Hhly3 and NisK/R were particularly enriched in human isolates, after stratification by genetic lineage and country of isolation. This systematic review and genomic meta-analysis has identified virulence factors that are likely to contribute to the zoonotic potential of <i>S. suis</i>.
DOI: 10.6084/m9.figshare.16834796.v2
title: Identification of <i>Streptococcus suis</i> putative zoonotic virulence factors: A systematic review and genomic meta-analysis

description: <i>Streptococcus suis</i> is an emerging zoonotic pathogen. Over 100 putative virulence factors have been described, but it is unclear to what extent these virulence factors could contribute to zoonotic potential of <i>S. suis</i>. We identified all <i>S. suis</i> virulence factors studied in experimental models of human origin in a systematic review and assessed their contribution to zoonotic potential in a subsequent genomic meta-analysis. PubMed and Scopus were searched for English-language articles that studied <i>S. suis</i> virulence published until 31 March 2021. Articles that analyzed a virulence factor by knockout mutation, purified protein, and/or recombinant protein in a model of human origin, were included. Data on virulence factor, strain characteristics, used human models and experimental outcomes were extracted. All publicly available <i>S. suis</i> genomes with available metadata on host, disease status and country of origin, were included in a genomic meta-analysis. We calculated the ratio of the prevalence of each virulence factor in human and pig isolates. We included 130 articles and 1703 <i>S. suis</i> genomes in the analysis. We identified 53 putative virulence factors that were encoded by genes which are part of the <i>S. suis</i> core genome and 26 factors that were at least twice as prevalent in human isolates as in pig isolates. Hhly3 and NisK/R were particularly enriched in human isolates, after stratification by genetic lineage and country of isolation. This systematic review and genomic meta-analysis have identified virulence factors that are likely to contribute to the zoonotic potential of <i>S. suis</i>.
DOI: 10.6084/m9.figshare.16699099
title: Deciphering of <i>Candida parapsilosis</i> induced immune response in <i>Drosophila melanogaster</i>

description: <i>Candida</i> infections are the most prevalent cause of serious human mycoses and are the third most common pathogens isolated from bloodstream infections in hospitalized patients. <i>C. parapsilosis</i> is a member of the <i>non-albicans</i> spp., which have a predilection for causing life-threatening disease in neonates and hospitalized pediatric patients. In this study, we utilized a <i>Drosophila melanogaster</i> infection model to analyze the immunological responses to <i>C. parapsilosis</i>. Our results demonstrate that the Toll pathway in <i>Drosophila</i> controls <i>C. parapsilosis</i> proliferation as the Toll signaling mutant <i>MyD88<sup>−/</sup></i><sup>−</sup> flies are highly susceptible to <i>C. parapsilosis</i>. We also confirmed that the <i>MyD88<sup>−/</sup></i><sup>−</sup> fly is a convenient invertebrate animal model to analyze virulence properties of different species and strains from the <i>C. parapsilosis sensu lato</i> complex as <i>C. orthopsilosis, C. metapsilosis</i> proved to be less virulent than <i>C. parapsilosis sensu stricto</i> and the <i>N</i>-mannan deficient <i>C. parapsilosis och1</i>Δ/Δ strain showed attenuated pathogenicity in this immunodeficient <i>Drosophila</i> background. We also found that Persephone protease is not required for detection and activation of Toll pathway during <i>C. parapsilosis</i> infection. Furthermore, we observed that <i>Drosophila</i> β-glucan receptor deficient flies where more sensitive to <i>C. parapsilosis</i> compared to wild-type flies; however, we could not find a clear dependence on the recognition of this receptor and the cell wall β-glucan exposure-induced host response. These studies establish this <i>D. melanogaster</i> infection model as an efficient tool in deciphering immune responses to <i>C. parapsilosis</i> as well as for assessing virulence factors produced by this emerging fungal predator.