cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.19367131.v1
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.19367131.v2
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.20368714
title: <i>Streptococcus mutans</i> PrsA mediates AtlA secretion contributing to extracellular DNA release and biofilm formation in the pathogenesis of infective endocarditis

description: The role of secretion chaperone-regulated virulence proteins in the pathogenesis of infective endocarditis (IE) induced by viridans streptococci such as <i>Streptococcus mutans</i> is unclear. In this study, we investigated the contribution of the foldase protein PrsA, a putative parvulin-type peptidyl-prolyl isomerase, to the pathogenesis of <i>S. mutans</i>-induced IE. We found that a <i>prsA</i>-deficient strain had reduced virulence in terms of formation of vegetation on damaged heart valves, as well as reduced autolysis activity, eDNA release and biofilm formation capacity. The secretion and surface exposure of AtlA <i>in vitro</i> was reduced in the <i>prsA</i>-deficient mutant strain, and complementation of recombinant AtlA in the culture medium restored a wild type biofilm phenotype of the <i>prsA</i>-deficient mutant strain. This result suggests that secretion and surface localization of AtlA is regulated by PrsA during biofilm formation. Together, these results demonstrate that <i>S. mutans</i> PrsA could regulate AtlA-mediated eDNA release to contribute to biofilm formation in the pathogenesis of IE.
DOI: 10.6084/m9.figshare.19430580
title: The AdcACB/AdcAII system is essential for zinc homeostasis and an important contributor of <i>Enterococcus faecalis</i> virulence

description: Bacterial pathogens require a variety of micronutrients for growth, including trace metals such as iron, manganese, and zinc (Zn). Despite their relative abundance in host environments, access to these metals is severely restricted during infection due to host-mediated defense mechanisms collectively known as nutritional immunity. Despite a growing appreciation of the importance of Zn in host-pathogen interactions, the mechanisms of Zn homeostasis and the significance of Zn to the pathophysiology of <i>E. faecalis</i>, a major pathogen of nosocomial and community-associated infections, have not been thoroughly investigated. Here, we show that <i>E. faecalis</i> encoded ABC-type transporter AdcACB and an orphan substrate-binding lipoprotein AdcAII that work cooperatively to maintain Zn homeostasis. Simultaneous inactivation of <i>adcA</i> and <i>adcAII</i> or the entire <i>adcACB</i> operon led to a significant reduction in intracellular Zn under Zn-restricted conditions and heightened sensitivity to Zn-chelating agents including human calprotectin, aberrant cell morphology, and impaired fitness in serum <i>ex vivo</i>. Additionally, inactivation of <i>adcACB</i> and <i>adcAII</i> significantly reduced bacterial tolerance toward cell envelope-targeting antibiotics. Finally, we showed that the AdcACB/AdcAII system contributes to <i>E. faecalis</i> virulence in a <i>Galleria mellonella</i> invertebrate infection model and in two catheter-associated mouse infection models that recapitulate many of the host conditions associated with enterococcal human infections. Collectively, this report reveals that high-affinity Zn import is important for the pathogenesis of <i>E. faecalis</i> establishing the surface-associated AdcA and AdcAII lipoproteins as potential therapeutic targets.
DOI: 10.6084/m9.figshare.19430580.v1
title: The AdcACB/AdcAII system is essential for zinc homeostasis and an important contributor of <i>Enterococcus faecalis</i> virulence

description: Bacterial pathogens require a variety of micronutrients for growth, including trace metals such as iron, manganese, and zinc (Zn). Despite their relative abundance in host environments, access to these metals is severely restricted during infection due to host-mediated defense mechanisms collectively known as nutritional immunity. Despite a growing appreciation of the importance of Zn in host-pathogen interactions, the mechanisms of Zn homeostasis and the significance of Zn to the pathophysiology of <i>E. faecalis</i>, a major pathogen of nosocomial and community-associated infections, have not been thoroughly investigated. Here, we show that <i>E. faecalis</i> encoded ABC-type transporter AdcACB and an orphan substrate-binding lipoprotein AdcAII that work cooperatively to maintain Zn homeostasis. Simultaneous inactivation of <i>adcA</i> and <i>adcAII</i> or the entire <i>adcACB</i> operon led to a significant reduction in intracellular Zn under Zn-restricted conditions and heightened sensitivity to Zn-chelating agents including human calprotectin, aberrant cell morphology, and impaired fitness in serum <i>ex vivo</i>. Additionally, inactivation of <i>adcACB</i> and <i>adcAII</i> significantly reduced bacterial tolerance toward cell envelope-targeting antibiotics. Finally, we showed that the AdcACB/AdcAII system contributes to <i>E. faecalis</i> virulence in a <i>Galleria mellonella</i> invertebrate infection model and in two catheter-associated mouse infection models that recapitulate many of the host conditions associated with enterococcal human infections. Collectively, this report reveals that high-affinity Zn import is important for the pathogenesis of <i>E. faecalis</i> establishing the surface-associated AdcA and AdcAII lipoproteins as potential therapeutic targets.
DOI: 10.6084/m9.figshare.19858908
title: Dual role of CsrA in regulating the hemolytic activity of <i>Escherichia coli</i> O157:H7

description: Post-transcriptional global carbon storage regulator A (CsrA) is a sequence-specific RNA-binding protein involved in the regulation of multiple bacterial processes. Hemolysin is an important virulence factor in the enterohemorrhagic <i>Escherichia coli</i> O157:H7 (EHEC). Here, we show that CsrA plays a dual role in the regulation of hemolysis in EHEC. CsrA significantly represses plasmid-borne enterohemolysin (EhxA)-mediated hemolysis and activates chromosome-borne hemolysin E (HlyE)-mediated hemolysis through different mechanisms. RNA structure prediction revealed a well-matched stem-loop structure with two potential CsrA binding sites located on the 5' untranslated region (UTR) of <i>ehxB</i>, which encodes a translocator required for EhxA secretion. CsrA inhibits EhxA secretion by directly binding to the RNA leader sequence of <i>ehxB</i> to repress its expression in two different ways: CsrA either binds to the Shine–Dalgarno sequence of <i>ehxB</i> to block ribosome access or to <i>ehxB</i> transcript to promote its mRNA decay. The predicted CsrA-binding site 1 of <i>ehxB</i> is essential for its regulation. There is a single potential CsrA-binding site at the 5'-end of the <i>hlyE</i> transcript, and its mutation completely abolishes CsrA-dependent activation. CsrA can also stabilize <i>hlyE</i> mRNA by directly binding to its 5' UTR. Overall, our results indicate that CsrA acts as a hemolysis modulator to regulate pathogenicity under certain conditions.
DOI: 10.6084/m9.figshare.19858908.v1
title: Dual role of CsrA in regulating the hemolytic activity of <i>Escherichia coli</i> O157:H7

description: Post-transcriptional global carbon storage regulator A (CsrA) is a sequence-specific RNA-binding protein involved in the regulation of multiple bacterial processes. Hemolysin is an important virulence factor in the enterohemorrhagic <i>Escherichia coli</i> O157:H7 (EHEC). Here, we show that CsrA plays a dual role in the regulation of hemolysis in EHEC. CsrA significantly represses plasmid-borne enterohemolysin (EhxA)-mediated hemolysis and activates chromosome-borne hemolysin E (HlyE)-mediated hemolysis through different mechanisms. RNA structure prediction revealed a well-matched stem-loop structure with two potential CsrA binding sites located on the 5' untranslated region (UTR) of <i>ehxB</i>, which encodes a translocator required for EhxA secretion. CsrA inhibits EhxA secretion by directly binding to the RNA leader sequence of <i>ehxB</i> to repress its expression in two different ways: CsrA either binds to the Shine–Dalgarno sequence of <i>ehxB</i> to block ribosome access or to <i>ehxB</i> transcript to promote its mRNA decay. The predicted CsrA-binding site 1 of <i>ehxB</i> is essential for its regulation. There is a single potential CsrA-binding site at the 5'-end of the <i>hlyE</i> transcript, and its mutation completely abolishes CsrA-dependent activation. CsrA can also stabilize <i>hlyE</i> mRNA by directly binding to its 5' UTR. Overall, our results indicate that CsrA acts as a hemolysis modulator to regulate pathogenicity under certain conditions.
DOI: 10.6084/m9.figshare.20368714.v1
title: <i>Streptococcus mutans</i> PrsA mediates AtlA secretion contributing to extracellular DNA release and biofilm formation in the pathogenesis of infective endocarditis

description: The role of secretion chaperone-regulated virulence proteins in the pathogenesis of infective endocarditis (IE) induced by viridans streptococci such as <i>Streptococcus mutans</i> is unclear. In this study, we investigated the contribution of the foldase protein PrsA, a putative parvulin-type peptidyl-prolyl isomerase, to the pathogenesis of <i>S. mutans</i>-induced IE. We found that a <i>prsA</i>-deficient strain had reduced virulence in terms of formation of vegetation on damaged heart valves, as well as reduced autolysis activity, eDNA release and biofilm formation capacity. The secretion and surface exposure of AtlA <i>in vitro</i> was reduced in the <i>prsA</i>-deficient mutant strain, and complementation of recombinant AtlA in the culture medium restored a wild type biofilm phenotype of the <i>prsA</i>-deficient mutant strain. This result suggests that secretion and surface localization of AtlA is regulated by PrsA during biofilm formation. Together, these results demonstrate that <i>S. mutans</i> PrsA could regulate AtlA-mediated eDNA release to contribute to biofilm formation in the pathogenesis of IE.
DOI: 10.6084/m9.figshare.20695497
title: Comparative transcriptomic analysis reveal genes involved in the pathogenicity increase of <i>Streptococcus suis</i> epidemic strains

description: <i>Streptococcus suis</i> epidemic strains were responsible for two outbreaks in China and possessed increased pathogenicity which was featured prominently by inducing an excessive inflammatory response at the early phase of infection. To discover the critical genes responsible for the pathogenicity increase of <i>S. suis</i> epidemic strains, the genome-wide transcriptional profiles of epidemic strain SC84 were investigated at the early phase of interaction with BV2 cells. The overall low expression levels of 89K pathogenicity island (PAI) and 129 known virulence genes in the SC84 interaction groups indicated that its pathogenicity increase should be attributed to novel mechanisms. Using highly pathogenic strain P1/7 and intermediately pathogenic strain 89–1591 as controls, 11 pathogenicity increase crucial genes (PICGs) and 38 pathogenicity increase-related genes (PIRGs) were identified in the SC84 incubation groups. The PICGs encoded proteins related to the methionine biosynthesis/uptake pathway and played critical roles in the pathogenicity increase of epidemic strains. A high proportion of PIRGs encoded surface proteins related to host cell adherence and immune escape, which may be conducive to the pathogenicity increase of epidemic strains by rapidly initiating infection. The fact that none of PICGs and PIRGs belonged to epidemic strain-specific gene indicated that the pathogenicity increase of epidemic strain may be determined by the expression level of genes, rather than the presence of them. Our results deepened the understanding on the mechanism of the pathogenicity increase of <i>S. suis</i> epidemic strains and provided novel approaches to control the life-threatening infections of <i>S. suis</i> epidemic strains.
DOI: 10.6084/m9.figshare.20695497.v1
title: Comparative transcriptomic analysis reveal genes involved in the pathogenicity increase of <i>Streptococcus suis</i> epidemic strains

description: <i>Streptococcus suis</i> epidemic strains were responsible for two outbreaks in China and possessed increased pathogenicity which was featured prominently by inducing an excessive inflammatory response at the early phase of infection. To discover the critical genes responsible for the pathogenicity increase of <i>S. suis</i> epidemic strains, the genome-wide transcriptional profiles of epidemic strain SC84 were investigated at the early phase of interaction with BV2 cells. The overall low expression levels of 89K pathogenicity island (PAI) and 129 known virulence genes in the SC84 interaction groups indicated that its pathogenicity increase should be attributed to novel mechanisms. Using highly pathogenic strain P1/7 and intermediately pathogenic strain 89–1591 as controls, 11 pathogenicity increase crucial genes (PICGs) and 38 pathogenicity increase-related genes (PIRGs) were identified in the SC84 incubation groups. The PICGs encoded proteins related to the methionine biosynthesis/uptake pathway and played critical roles in the pathogenicity increase of epidemic strains. A high proportion of PIRGs encoded surface proteins related to host cell adherence and immune escape, which may be conducive to the pathogenicity increase of epidemic strains by rapidly initiating infection. The fact that none of PICGs and PIRGs belonged to epidemic strain-specific gene indicated that the pathogenicity increase of epidemic strain may be determined by the expression level of genes, rather than the presence of them. Our results deepened the understanding on the mechanism of the pathogenicity increase of <i>S. suis</i> epidemic strains and provided novel approaches to control the life-threatening infections of <i>S. suis</i> epidemic strains.
DOI: 10.6084/m9.figshare.20318755
title: Recombination events drives the emergence of Colombian <i>Helicobacter pylori</i> subpopulations with self-identity ancestry

description: <i>Helicobacter pylori</i> have coevolved with mankind since its origins, adapting to different human groups. In America, <i>H. pylori</i> has evolved into several subpopulations. We analysed the genome of 154 Colombian strains along with 1,091 strains from worldwide populations to discern the ancestry and adaption to Colombian people. Population structure and ancestry was inferred with FineStructure and ChromoPainter. Phylogenetic relationship and the relative effect of recombination were analysing the core SNPs. Also, a Fst index was calculated to identify the gene variants with the strongest fixation in the Colombian subpopulations compared to their parent population <i>hspSWEurope</i>. FineStructure allowed the identification of two Colombian subpopulations, the previously described <i>hspSWEuropeColombia</i> and a novel subpopulation named <i>hspColombia</i>, that included three subgroups following their geographic origin. Colombian subpopulations represent an admixture of European, African and Indigenous ancestry; although some genomes showed a high proportion of self identity, suggesting an advanced adaption to these mestizo Colombian groups. We found that recombination is more important that punctual mutations in <i>H. pylori</i> genome diversity, 13.9 more important in <i>hspSWEurope</i>, 12.5 in <i>hspSWEColombia</i> and 10.5 in <i>hspColombia</i>, reflecting the divergence of these subpopulations. Fst analysis identified 82 SNPs fixed in 26 genes of the <i>hspColombia</i> subpopulation that encode for outer membrane and central metabolism proteins. Strongest fixation indexes were identified in genes encoding HofC, HopE, FrpB-4 and Sialidase A. These findings demonstrate that <i>H. pylori</i> has evolved in Colombia to give rise to subpopulations with a self identity ancestry, reflected in allele changes on genes encoding for outer membrane proteins.
DOI: 10.6084/m9.figshare.20318755.v1
title: Recombination events drives the emergence of Colombian <i>Helicobacter pylori</i> subpopulations with self-identity ancestry

description: <i>Helicobacter pylori</i> have coevolved with mankind since its origins, adapting to different human groups. In America, <i>H. pylori</i> has evolved into several subpopulations. We analysed the genome of 154 Colombian strains along with 1,091 strains from worldwide populations to discern the ancestry and adaption to Colombian people. Population structure and ancestry was inferred with FineStructure and ChromoPainter. Phylogenetic relationship and the relative effect of recombination were analysing the core SNPs. Also, a Fst index was calculated to identify the gene variants with the strongest fixation in the Colombian subpopulations compared to their parent population <i>hspSWEurope</i>. FineStructure allowed the identification of two Colombian subpopulations, the previously described <i>hspSWEuropeColombia</i> and a novel subpopulation named <i>hspColombia</i>, that included three subgroups following their geographic origin. Colombian subpopulations represent an admixture of European, African and Indigenous ancestry; although some genomes showed a high proportion of self identity, suggesting an advanced adaption to these mestizo Colombian groups. We found that recombination is more important that punctual mutations in <i>H. pylori</i> genome diversity, 13.9 more important in <i>hspSWEurope</i>, 12.5 in <i>hspSWEColombia</i> and 10.5 in <i>hspColombia</i>, reflecting the divergence of these subpopulations. Fst analysis identified 82 SNPs fixed in 26 genes of the <i>hspColombia</i> subpopulation that encode for outer membrane and central metabolism proteins. Strongest fixation indexes were identified in genes encoding HofC, HopE, FrpB-4 and Sialidase A. These findings demonstrate that <i>H. pylori</i> has evolved in Colombia to give rise to subpopulations with a self identity ancestry, reflected in allele changes on genes encoding for outer membrane proteins.
DOI: 10.6084/m9.figshare.20524685
title: SLC1A3 facilitates Newcastle disease virus replication by regulating glutamine catabolism

description: As obligate intracellular parasites, viruses rely completely on host metabolic machinery and hijack host nutrients for viral replication. Newcastle disease virus (NDV) causes acute, highly contagious avian disease and functions as an oncolytic agent. NDV efficiently replicates in both chicken and tumour cells. However, how NDV reprograms host cellular metabolism for its efficient replication is still ill-defined. We previously identified a significantly upregulated glutamate transporter gene, solute carrier family 1 member 3 (<i>SLC1A3</i>), during NDV infection via transcriptome analysis. To investigate the potential role of <i>SLC1A3</i> during NDV infection, we first confirmed the marked upregulation of <i>SLC1A3</i> in NDV-infected DF-1 or A549 cells through p53 and NF-κB pathways. Knockdown of <i>SLC1A3</i> inhibited NDV infection. Western blot analysis further confirmed that glutamine, but not glutamate, asparagine, or aspartate, was required for NDV replication. Metabolic flux data showed that NDV promotes the decomposition of glutamine into the tricarboxylic acid cycle. Importantly, the level of glutamate and glutaminolysis were reduced by <i>SLC1A3</i> knockdown, indicating that <i>SLC1A3</i> propelled glutaminolysis for glutamate utilization and NDV replication in host cells. Taken together, our data identify that <i>SLC1A3</i> serves as an important regulator for glutamine metabolism and is hijacked by NDV for its efficient replication during NDV infection. These results improve our understanding of the interaction between NDV and host cellular metabolism and lay the foundation for further investigation of efficient vaccines.