cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.14844591
title: Genetic architecture of transmission stage production and virulence in schistosome parasites

description: Both theory and experimental data from pathogens suggest that the production of transmission stages should be strongly associated with virulence, but the genetic bases of parasite transmission/virulence traits are poorly understood. The blood fluke <i>Schistosoma mansoni</i> shows extensive variation in numbers of cercariae larvae shed and in their virulence to infected snail hosts, consistent with expected trade-offs between parasite transmission and virulence. We crossed schistosomes from two populations that differ 8-fold in cercarial shedding and in their virulence to <i>Biomphalaria glabrata</i> snail hosts, and determined four-week cercarial shedding profiles in F0 parents, F1 parents and 376 F2 progeny from two independent crosses in inbred snails. Sequencing and linkage analysis revealed that cercarial production is polygenic and controlled by five QTLs (i.e. Quantitative Trait Loci). These QTLs act additively, explaining 28.56% of the phenotypic variation. These results demonstrate that the genetic architecture of key traits relevant to schistosome ecology can be dissected using classical linkage mapping approaches.
DOI: 10.6084/m9.figshare.14844591.v1
title: Genetic architecture of transmission stage production and virulence in schistosome parasites

description: Both theory and experimental data from pathogens suggest that the production of transmission stages should be strongly associated with virulence, but the genetic bases of parasite transmission/virulence traits are poorly understood. The blood fluke <i>Schistosoma mansoni</i> shows extensive variation in numbers of cercariae larvae shed and in their virulence to infected snail hosts, consistent with expected trade-offs between parasite transmission and virulence. We crossed schistosomes from two populations that differ 8-fold in cercarial shedding and in their virulence to <i>Biomphalaria glabrata</i> snail hosts, and determined four-week cercarial shedding profiles in F0 parents, F1 parents and 376 F2 progeny from two independent crosses in inbred snails. Sequencing and linkage analysis revealed that cercarial production is polygenic and controlled by five QTLs (i.e. Quantitative Trait Loci). These QTLs act additively, explaining 28.56% of the phenotypic variation. These results demonstrate that the genetic architecture of key traits relevant to schistosome ecology can be dissected using classical linkage mapping approaches.
DOI: 10.6084/m9.figshare.17041679
title: Emergent SARS-CoV-2 variants: comparative replication dynamics and high sensitivity to thapsigargin

description: The struggle to control the COVID-19 pandemic is made challenging by the emergence of virulent SARS-CoV-2 variants. To gain insight into their replication dynamics, emergent Alpha (A), Beta (B) and Delta (D) SARS-CoV-2 variants were assessed for their infection performance in single variant- and co-infections. The effectiveness of thapsigargin (TG), a recently discovered broad-spectrum antiviral, against these variants was also examined. Of the 3 viruses, the D variant exhibited the highest replication rate and was most able to spread to in-contact cells; its replication rate at 24 h post-infection (hpi) based on progeny viral RNA production was over 4 times that of variant A and 9 times more than the B variant. In co-infections, the D variant boosted the replication of its co-infected partners at the expense of its own initial performance. Furthermore, co-infection with AD or AB combination conferred replication synergy where total progeny (RNA) output was greater than the sum of corresponding single-variant infections. All variants were highly sensitive to TG inhibition. A single pre-infection priming dose of TG effectively blocked all single-variant infections and every combination (AB, AD, BD variants) of co-infection at greater than 95% (relative to controls) at 72 hpi. Likewise, TG was effective in inhibiting each variant in active preexisting infection. In conclusion, against the current backdrop of the dominant D variant that could be further complicated by co-infection synergy with new variants, the growing list of viruses susceptible to TG, a promising host-centric antiviral, now includes a spectrum of contemporary SARS-CoV-2 viruses.
DOI: 10.6084/m9.figshare.14815955
title: YhjC is a novel transcriptional regulator required for Shigella flexneri virulence

description: <i>Shigella</i> is an intracellular pathogen that primarily infects the human colon and causes shigellosis. <i>Shigella</i> virulence relies largely on the type III secretion system (T3SS) and secreted effectors. VirF, the master <i>Shigella</i> virulence regulator, is essential for the expression of T3SS-related genes. In this study, we found that YhjC, a LysR-type transcriptional regulator, is required for <i>Shigella</i> virulence through activating the transcription of <i>virF</i>. Pathogenicity of the <i>yhjC</i> mutant, including colonization in the colons of guinea pigs as well as its ability for host cell adhesion and invasion, was significantly lowered. Expression levels of <i>virF</i> and nearly all VirF-dependent genes were downregulated by <i>yhjC</i> deletion, indicating that YhjC can activate <i>virF</i> transcription. Electrophoretic mobility shift assay analysis demonstrated that YhjC could bind directly to the <i>virF</i> promoter region. Therefore, YhjC is a novel virulence regulator that positively regulates the <i>virF</i> expression and promotes <i>Shigella</i> virulence. Additionally, genome-wide expression analysis identified the presence of other genes in the large virulence plasmid and a genome exhibiting differential expression in response to <i>yhjC</i> deletion, with 169 downregulated and 99 upregulated genes, indicating that YhjC also functioned as a global regulatory factor.
DOI: 10.6084/m9.figshare.14815955.v1
title: YhjC is a novel transcriptional regulator required for Shigella flexneri virulence

description: <i>Shigella</i> is an intracellular pathogen that primarily infects the human colon and causes shigellosis. <i>Shigella</i> virulence relies largely on the type III secretion system (T3SS) and secreted effectors. VirF, the master <i>Shigella</i> virulence regulator, is essential for the expression of T3SS-related genes. In this study, we found that YhjC, a LysR-type transcriptional regulator, is required for <i>Shigella</i> virulence through activating the transcription of <i>virF</i>. Pathogenicity of the <i>yhjC</i> mutant, including colonization in the colons of guinea pigs as well as its ability for host cell adhesion and invasion, was significantly lowered. Expression levels of <i>virF</i> and nearly all VirF-dependent genes were downregulated by <i>yhjC</i> deletion, indicating that YhjC can activate <i>virF</i> transcription. Electrophoretic mobility shift assay analysis demonstrated that YhjC could bind directly to the <i>virF</i> promoter region. Therefore, YhjC is a novel virulence regulator that positively regulates the <i>virF</i> expression and promotes <i>Shigella</i> virulence. Additionally, genome-wide expression analysis identified the presence of other genes in the large virulence plasmid and a genome exhibiting differential expression in response to <i>yhjC</i> deletion, with 169 downregulated and 99 upregulated genes, indicating that YhjC also functioned as a global regulatory factor.
DOI: 10.6084/m9.figshare.17282729
title: Paeoniflorin reduce <i>luxS</i>/AI-2 system-controlled biofilm formation and virulence in <i>Streptococcus suis</i>

description: <i>Streptococcus suis</i> (<i>S. suis</i>), more specifically serotype 2, is a bacterial pathogen that threatens the lives of pigs and humans. Like many other pathogens, <i>S. suis</i> exhibits quorum sensing (QS) system-controlled virulence factors, such as biofilm formation that complicates treatment. Therefore, impairing the QS involving LuxS/AI-2 cycle in <i>S. suis</i>, may be a promising alternative strategy for overcoming <i>S. suis</i> infections. In this study, we investigated paeoniflorin (PF), a monoterpenoid glycoside compound extracted from peony, as an inhibitor of <i>S. suis</i> LuxS/AI-2 system. At a sub-minimal inhibitory concentration (MIC) (1/16 MIC; 25 μg/ml), PF significantly reduced biofilm formation by <i>S. suis</i> through inhibition of extracellular polysaccharide (EPS) production, without affecting bacterial growth. Moreover, evidence was brought that PF reduces AI-2 activity in <i>S. suis</i> biofilm. Molecular docking indicated that LuxS may be the target of PF. Monitoring LuxS enzymatic activity confirmed that PF had a partial inhibitory effect. Finally, we showed that the use of PF in a mouse model can relieve <i>S. suis</i> infections. This study highlighted the anti-biofilm potential of PF against <i>S. suis</i>, and brought evidence that it may as an inhibitor of the LuxS/AI-2 system to prevent <i>S. suis</i> biofilm-related infections. PF can thus be used as a new type of natural biofilm inhibitor for clinical application.
DOI: 10.6084/m9.figshare.17282729.v1
title: Paeoniflorin reduce <i>luxS</i>/AI-2 system-controlled biofilm formation and virulence in <i>Streptococcus suis</i>

description: <i>Streptococcus suis</i> (<i>S. suis</i>), more specifically serotype 2, is a bacterial pathogen that threatens the lives of pigs and humans. Like many other pathogens, <i>S. suis</i> exhibits quorum sensing (QS) system-controlled virulence factors, such as biofilm formation that complicates treatment. Therefore, impairing the QS involving LuxS/AI-2 cycle in <i>S. suis</i>, may be a promising alternative strategy for overcoming <i>S. suis</i> infections. In this study, we investigated paeoniflorin (PF), a monoterpenoid glycoside compound extracted from peony, as an inhibitor of <i>S. suis</i> LuxS/AI-2 system. At a sub-minimal inhibitory concentration (MIC) (1/16 MIC; 25 μg/ml), PF significantly reduced biofilm formation by <i>S. suis</i> through inhibition of extracellular polysaccharide (EPS) production, without affecting bacterial growth. Moreover, evidence was brought that PF reduces AI-2 activity in <i>S. suis</i> biofilm. Molecular docking indicated that LuxS may be the target of PF. Monitoring LuxS enzymatic activity confirmed that PF had a partial inhibitory effect. Finally, we showed that the use of PF in a mouse model can relieve <i>S. suis</i> infections. This study highlighted the anti-biofilm potential of PF against <i>S. suis</i>, and brought evidence that it may as an inhibitor of the LuxS/AI-2 system to prevent <i>S. suis</i> biofilm-related infections. PF can thus be used as a new type of natural biofilm inhibitor for clinical application.
DOI: 10.6084/m9.figshare.14529909
title: Decreased temperature increases the expression of a disordered bacterial late embryogenesis abundant (LEA) protein that enhances natural transformation

description: Late embryogenesis abundant (LEA) proteins are important players in the management of responses to stressful conditions, such as drought, high salinity, and changes in temperature. Many LEA proteins do not have defined three-dimensional structures, so they are intrinsically disordered proteins (IDPs) and are often highly hydrophilic. Although LEA-like sequences have been identified in bacterial genomes, the functions of bacterial LEA proteins have been studied only recently. Sequence analysis of outer membrane interleukin receptor I (BilRI) from the oral pathogen <i>Aggregatibacter actinomycetemcomitans</i> indicated that it shared sequence similarity with group 3/3b/4 LEA proteins. Comprehensive nuclearcgq
magnetic resonance (NMR) studies confirmed its IDP nature, and expression studies in <i>A. actinomycetemcomitans</i> harboring a red fluorescence reporter protein-encoding gene revealed that <i>bilRI</i> promoter expression was increased at decreased temperatures. The amino acid backbone of BilRI did not stimulate either the production of reactive oxygen species from human leukocytes or the production of interleukin-6 from human macrophages. Moreover, BilRI-specific IgG antibodies could not be detected in the sera of <i>A. actinomycetemcomitans</i> culture-positive periodontitis patients. Since the <i>bilRI</i> gene is located near genes involved in natural competence (i.e., genes associated with the uptake of extracellular (eDNA) and its incorporation into the genome), we also investigated the role of BilRI in these events. Compared to wild-type cells, the Δ<i>bilRI</i> mutants showed a lower transformation efficiency, which indicates either a direct or indirect role in natural competence. In conclusion, <i>A. actinomycetemcomitans</i> might express BilRI, especially outside the host, to survive under stressful conditions and improve its transmission potential.
DOI: 10.6084/m9.figshare.14529909.v1
title: Decreased temperature increases the expression of a disordered bacterial late embryogenesis abundant (LEA) protein that enhances natural transformation

description: Late embryogenesis abundant (LEA) proteins are important players in the management of responses to stressful conditions, such as drought, high salinity, and changes in temperature. Many LEA proteins do not have defined three-dimensional structures, so they are intrinsically disordered proteins (IDPs) and are often highly hydrophilic. Although LEA-like sequences have been identified in bacterial genomes, the functions of bacterial LEA proteins have been studied only recently. Sequence analysis of outer membrane interleukin receptor I (BilRI) from the oral pathogen <i>Aggregatibacter actinomycetemcomitans</i> indicated that it shared sequence similarity with group 3/3b/4 LEA proteins. Comprehensive nuclearcgq
magnetic resonance (NMR) studies confirmed its IDP nature, and expression studies in <i>A. actinomycetemcomitans</i> harboring a red fluorescence reporter protein-encoding gene revealed that <i>bilRI</i> promoter expression was increased at decreased temperatures. The amino acid backbone of BilRI did not stimulate either the production of reactive oxygen species from human leukocytes or the production of interleukin-6 from human macrophages. Moreover, BilRI-specific IgG antibodies could not be detected in the sera of <i>A. actinomycetemcomitans</i> culture-positive periodontitis patients. Since the <i>bilRI</i> gene is located near genes involved in natural competence (i.e., genes associated with the uptake of extracellular (eDNA) and its incorporation into the genome), we also investigated the role of BilRI in these events. Compared to wild-type cells, the Δ<i>bilRI</i> mutants showed a lower transformation efficiency, which indicates either a direct or indirect role in natural competence. In conclusion, <i>A. actinomycetemcomitans</i> might express BilRI, especially outside the host, to survive under stressful conditions and improve its transmission potential.
DOI: 10.6084/m9.figshare.14931567
title: Suppressed inflammation in obese children induced by a high-fiber diet is associated with the attenuation of gut microbial virulence factor genes

description: In our previous study, a gut microbiota-targeted dietary intervention with a high-fiber diet improved the immune status of both genetically obese (Prader-Willi Syndrome, PWS) and simple obese (SO) children. However, PWS children had higher inflammation levels than SO children throughout the trial, the gut microbiota of the two cohorts was similar. As some virulence factors (VFs) produced by the gut microbiota play a role in triggering host inflammation, this study compared the characteristics and changes of gut microbial VF genes of the two cohorts before and after the intervention using a fecal metagenomic dataset. We found that in both cohorts, the high-fiber diet reduced the abundance of VF, and particularly pathogen-specific, genes. The composition of VF genes was also modulated, especially for offensive and defensive VF genes. Furthermore, genes belonging to invasion, T3SS (type III secretion system), and adherence classes were suppressed. Co-occurrence network analysis detected VF gene clusters closely related to host inflammation in each cohort. Though these cohort-specific clusters varied in VF gene combinations and cascade reactions affecting inflammation, they mainly contained VFs belonging to iron uptake, T3SS, and invasion classes. The PWS group had a lower abundance of VF genes before the trial, which suggested that other factors could also be responsible for the increased inflammation in this cohort. This study provides insight into the modulation of VF gene structure in the gut microbiota by a high-fiber diet, with respect to reduced inflammation in obese children, and differences in VF genes between these two cohorts.
DOI: 10.6084/m9.figshare.14931567.v1
title: Suppressed inflammation in obese children induced by a high-fiber diet is associated with the attenuation of gut microbial virulence factor genes

description: In our previous study, a gut microbiota-targeted dietary intervention with a high-fiber diet improved the immune status of both genetically obese (Prader-Willi Syndrome, PWS) and simple obese (SO) children. However, PWS children had higher inflammation levels than SO children throughout the trial, the gut microbiota of the two cohorts was similar. As some virulence factors (VFs) produced by the gut microbiota play a role in triggering host inflammation, this study compared the characteristics and changes of gut microbial VF genes of the two cohorts before and after the intervention using a fecal metagenomic dataset. We found that in both cohorts, the high-fiber diet reduced the abundance of VF, and particularly pathogen-specific, genes. The composition of VF genes was also modulated, especially for offensive and defensive VF genes. Furthermore, genes belonging to invasion, T3SS (type III secretion system), and adherence classes were suppressed. Co-occurrence network analysis detected VF gene clusters closely related to host inflammation in each cohort. Though these cohort-specific clusters varied in VF gene combinations and cascade reactions affecting inflammation, they mainly contained VFs belonging to iron uptake, T3SS, and invasion classes. The PWS group had a lower abundance of VF genes before the trial, which suggested that other factors could also be responsible for the increased inflammation in this cohort. This study provides insight into the modulation of VF gene structure in the gut microbiota by a high-fiber diet, with respect to reduced inflammation in obese children, and differences in VF genes between these two cohorts.
DOI: 10.6084/m9.figshare.16786633
title: Quantitative proteomics reveals that dormancy-related proteins mediate the attenuation in mycobacterium strains

description: Although members of the <i>Mycobacterium tuberculosis</i> complex (MTBC) exhibit high similarity, they are characterized by differences with respect to virulence, immune response, and transmissibility. To understand the virulence of these bacteria and identify potential novel therapeutic targets, we systemically investigated the total cell protein contents of virulent H37Rv, attenuated H37Ra, and avirulent <i>M. bovis</i> BCG vaccine strains at the log and stationary phases, based on tandem mass tag (TMT) quantitative proteomics. Data analysis revealed that we obtained deep-coverage protein identification and high quantification. Although 272 genetic variations were reported in H37Ra and H37Rv, they showed very little expression difference in log and stationary phase. Quantitative comparison revealed H37Ra and H37Rv had significantly dysregulation in log phase (227) compared with stationary phase (61). While BCG and H37Rv, and BCG and H37Ra showed notable differences in stationary phase (1171 and 1124) with respect to log phase (381 and 414). In the log phase, similar patterns of protein abundance were observed between H37Ra and BCG, whereas a more similar expression pattern was observed between H37Rv and H37Ra in the stationary phase. Bioinformatic analysis revealed that the upregulated proteins detected for H37Rv and H37Ra in log phase were virulence-related factors. In both log and stationary phases, the dysregulated proteins detected for BCG, which have also been identified as <i>M. tuberculosis</i> response proteins under dormancy conditions. We accordingly describe the proteomic profiles of H37Rv, H37Ra, and BCG, which we believe will potentially provide a better understanding of H37Rv pathogenesis, H37Ra attenuation, and BCG immuno protection.
DOI: 10.6084/m9.figshare.16786633.v1
title: Quantitative proteomics reveals that dormancy-related proteins mediate the attenuation in mycobacterium strains

description: Although members of the <i>Mycobacterium tuberculosis</i> complex (MTBC) exhibit high similarity, they are characterized by differences with respect to virulence, immune response, and transmissibility. To understand the virulence of these bacteria and identify potential novel therapeutic targets, we systemically investigated the total cell protein contents of virulent H37Rv, attenuated H37Ra, and avirulent <i>M. bovis</i> BCG vaccine strains at the log and stationary phases, based on tandem mass tag (TMT) quantitative proteomics. Data analysis revealed that we obtained deep-coverage protein identification and high quantification. Although 272 genetic variations were reported in H37Ra and H37Rv, they showed very little expression difference in log and stationary phase. Quantitative comparison revealed H37Ra and H37Rv had significantly dysregulation in log phase (227) compared with stationary phase (61). While BCG and H37Rv, and BCG and H37Ra showed notable differences in stationary phase (1171 and 1124) with respect to log phase (381 and 414). In the log phase, similar patterns of protein abundance were observed between H37Ra and BCG, whereas a more similar expression pattern was observed between H37Rv and H37Ra in the stationary phase. Bioinformatic analysis revealed that the upregulated proteins detected for H37Rv and H37Ra in log phase were virulence-related factors. In both log and stationary phases, the dysregulated proteins detected for BCG, which have also been identified as <i>M. tuberculosis</i> response proteins under dormancy conditions. We accordingly describe the proteomic profiles of H37Rv, H37Ra, and BCG, which we believe will potentially provide a better understanding of H37Rv pathogenesis, H37Ra attenuation, and BCG immuno protection.