cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.27888075.v1
title: DNA damage repair factor Rad18 controls virulence partially via transcriptional suppression of genes <i>HWP1</i> and <i>ECE1</i> in <i>Candida albicans</i>

description: DNA damage repair is a crucial cellular mechanism for rectifying DNA lesions arising during growth and development. Among the various repair pathways, postreplication repair (PRR) plays a pivotal role in resolving single-stranded gaps induced by DNA damage. However, the contribution of PRR to virulence remains elusive in the fungal pathogen <i>Candida albicans (C. albicans)</i>. In this study, we investigated the role of Rad18, a critical component of PRR, in DNA damage response and virulence in <i>C. albicans</i>. We observed that deletion of <i>RAD18</i> in <i>C. albicans</i> resulted in heightened sensitivity to DNA damage stress. Through deletion of specific internal domains coupled with spot assay analysis, we show that the internal RING and SAP domains play essential roles in DNA damage response, whereas the ZNF domain was less important. Surprisingly, the lack of Rad18 in <i>C. albicans</i> resulted in heightened intracellular survival within macrophages and elevated virulence in the <i>Galleria mellonella</i> model. RNAseq analysis revealed that loss of Rad18 upregulated the transcription of genes encoding transporters and oxidoreductases, as well as virulence genes, including <i>HWP1</i> and <i>ECE1</i>. Suppression of the transcription of these virulence genes in the <i>RAD18</i> deletion strain by a dCas9-mediated CRISPRi system reversed this increased virulence. Taken together, these data demonstrate that Rad18 plays a significant role in virulence partially through transcriptional suppression of virulence genes <i>HWP1</i> and <i>ECE1</i> in <i>C. albicans</i>. Our findings provide valuable insights into the intricate relationship between DNA damage response and virulence in <i>C. albicans</i>.
DOI: 10.6084/m9.figshare.26483573
title: Genome-wide characterization of structure variations in the Xiang pig for genetic resistance to African swine fever

description: African swine fever (ASF) is a rapidly fatal viral haemorrhagic fever in Chinese domestic pigs. Although very high mortality is observed in pig farms after an ASF outbreak, clinically healthy and antibody-positive pigs are found in those farms, and viral detection is rare from these pigs. The ability of pigs to resist ASF viral infection may be modulated by host genetic variations. However, the genetic basis of the resistance of domestic pigs against ASF remains unclear. We generated a comprehensive set of structural variations (SVs) in a Chinese indigenous Xiang pig with ASF-resistant (Xiang-R) and ASF-susceptible (Xiang-S) phenotypes using whole-genome resequencing method. A total of 53,589 nonredundant SVs were identified, with an average of 25,656 SVs per individual in the Xiang pig genome, including insertion, deletion, inversion and duplication variations. The Xiang-R group harboured more SVs than the Xiang-S group. The F-statistics (<i>F</i><sub>ST</sub>) was carried out to reveal genetic differences between two populations using the resequencing data at each SV locus. We identified 2,414 population-stratified SVs and annotated 1,152 Ensembl genes (including 986 protein-coding genes), in which 1,326 SVs might disturb the structure and expression of the Ensembl genes. Those protein-coding genes were mainly enriched in the Wnt, Hippo, and calcium signalling pathways. Other important pathways associated with the ASF viral infection were also identified, such as the endocytosis, apoptosis, focal adhesion, Fc gamma R-mediated phagocytosis, junction, NOD-like receptor, PI3K-Akt, and c-type lectin receptor signalling pathways. Finally, we identified 135 candidate adaptive genes overlapping 166 SVs that were involved in the virus entry and virus-host cell interactions. The fact that some of population-stratified SVs regions detected as selective sweep signals gave another support for the genetic variations affecting pig resistance against ASF. The research indicates that SVs play an important role in the evolutionary processes of Xiang pig adaptation to ASF infection.
DOI: 10.6084/m9.figshare.26483573.v1
title: Genome-wide characterization of structure variations in the Xiang pig for genetic resistance to African swine fever

description: African swine fever (ASF) is a rapidly fatal viral haemorrhagic fever in Chinese domestic pigs. Although very high mortality is observed in pig farms after an ASF outbreak, clinically healthy and antibody-positive pigs are found in those farms, and viral detection is rare from these pigs. The ability of pigs to resist ASF viral infection may be modulated by host genetic variations. However, the genetic basis of the resistance of domestic pigs against ASF remains unclear. We generated a comprehensive set of structural variations (SVs) in a Chinese indigenous Xiang pig with ASF-resistant (Xiang-R) and ASF-susceptible (Xiang-S) phenotypes using whole-genome resequencing method. A total of 53,589 nonredundant SVs were identified, with an average of 25,656 SVs per individual in the Xiang pig genome, including insertion, deletion, inversion and duplication variations. The Xiang-R group harboured more SVs than the Xiang-S group. The F-statistics (<i>F</i><sub>ST</sub>) was carried out to reveal genetic differences between two populations using the resequencing data at each SV locus. We identified 2,414 population-stratified SVs and annotated 1,152 Ensembl genes (including 986 protein-coding genes), in which 1,326 SVs might disturb the structure and expression of the Ensembl genes. Those protein-coding genes were mainly enriched in the Wnt, Hippo, and calcium signalling pathways. Other important pathways associated with the ASF viral infection were also identified, such as the endocytosis, apoptosis, focal adhesion, Fc gamma R-mediated phagocytosis, junction, NOD-like receptor, PI3K-Akt, and c-type lectin receptor signalling pathways. Finally, we identified 135 candidate adaptive genes overlapping 166 SVs that were involved in the virus entry and virus-host cell interactions. The fact that some of population-stratified SVs regions detected as selective sweep signals gave another support for the genetic variations affecting pig resistance against ASF. The research indicates that SVs play an important role in the evolutionary processes of Xiang pig adaptation to ASF infection.
DOI: 10.6084/m9.figshare.26936154.v2
title: YjbH contributes to <i>Staphylococcus aureus</i> skin pathology and immune response through Agr-mediated α-toxin regulation

description: <i>Staphylococcus aureus</i> is the most common cause of skin and soft tissue infections (SSTIs) with Methicillin-Resistant <i>S. aureus</i> (MRSA) strains being a major contributor in both community and hospital settings. <i>S. aureus</i> relies on metabolic diversity and a large repertoire of virulence factors to cause disease. This includes α-hemolysin (Hla), an integral player in tissue damage found in various models, including SSTIs. Previously, we identified a role for the Spx adapter protein, YjbH, in the regulation of several virulence factors and as an inhibitor of pathogenesis in a sepsis model. In this study, we found that YjbH is critical for tissue damage during SSTI, and its absence leads to decreased proinflammatory chemokines and cytokines in the skin. We identified no contribution of YjbI, encoded on the same transcript as YjbH. Using a combination of reporters and quantitative hemolysis assays, we demonstrated that YjbH impacts Hla expression and activity both <i>in vitro</i> and <i>in vivo</i>. Additionally, expression of Hla from a non-native promoter reversed the tissue damage phenotype of the Δ<i>yjbIH</i> mutant. Lastly, we identified reduced Agr activity as the likely cause for reduced Hla production in the Δ<i>yjbH</i> mutant. This work continues to define the importance of YjbH in the pathogenesis of <i>S. aureus</i> infection as well as identify a new pathway important for Hla production.
DOI: 10.6084/m9.figshare.27187401
title: Multifaceted roles of NADPH oxidases in the growth and pathogenicity of <i>Beauveria bassiana</i>

description: Reactive oxygen species (ROS), synthesized by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) complex, are vital molecules in biological cells, influencing various physiological processes such as fungal growth, development, and virulence. <i>Beauveria bassiana</i>, an entomopathogenic fungus, is a promising biopesticide for agricultural, forestry, and urban pest control. This study focuses on the characterization of NADPH oxidases (Noxs) in <i>B. bassiana</i>. Gene expression profiles of Noxs in <i>B. bassiana</i> (BbNoxs) were analysed using RT-qPCR. Knockout strains of single BbNoxA, BbNoxB, BbNoxR, and double BbNoxA and BbNoxB were constructed via homologous recombination, and their phenotypic characteristics were examined. Fungal virulence was evaluated using Galleria mellonella larvae, and infection structures formation and penetration ability were assessed on cicada wings. ROS production and actin assembly during fungal growth and infection were detected using staining and marker methods. Expression analysis revealed significant upregulation of BbNoxs during fungal growth and infection. Compared to the wild-type strain, single knockouts (ΔBbNoxA/B/R) and double knockout (ΔBbNoxAB) of BbNoxs exhibited reduced conidial yields, accelerated conidial germination rates. Deletion of BbNoxB or BbNoxR decreased fungal virulence compared to the WT strain in topical inoculation experiments. Additionally, loss of BbNoxB or BbNoxR impaired infection structures formation, penetration ability, ROS production, and actin aggregation during fungal infection. BbNoxs are crucial for fungal growth, development, and virulence in <i>B. bassiana</i>, playing essential roles in infection structures formation, penetration, ROS production, and actin assembly. Understanding their functions provides insights into <i>B. bassiana</i>’s pathogenic mechanisms.
DOI: 10.6084/m9.figshare.27187401.v1
title: Multifaceted roles of NADPH oxidases in the growth and pathogenicity of <i>Beauveria bassiana</i>

description: Reactive oxygen species (ROS), synthesized by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) complex, are vital molecules in biological cells, influencing various physiological processes such as fungal growth, development, and virulence. <i>Beauveria bassiana</i>, an entomopathogenic fungus, is a promising biopesticide for agricultural, forestry, and urban pest control. This study focuses on the characterization of NADPH oxidases (Noxs) in <i>B. bassiana</i>. Gene expression profiles of Noxs in <i>B. bassiana</i> (BbNoxs) were analysed using RT-qPCR. Knockout strains of single BbNoxA, BbNoxB, BbNoxR, and double BbNoxA and BbNoxB were constructed via homologous recombination, and their phenotypic characteristics were examined. Fungal virulence was evaluated using Galleria mellonella larvae, and infection structures formation and penetration ability were assessed on cicada wings. ROS production and actin assembly during fungal growth and infection were detected using staining and marker methods. Expression analysis revealed significant upregulation of BbNoxs during fungal growth and infection. Compared to the wild-type strain, single knockouts (ΔBbNoxA/B/R) and double knockout (ΔBbNoxAB) of BbNoxs exhibited reduced conidial yields, accelerated conidial germination rates. Deletion of BbNoxB or BbNoxR decreased fungal virulence compared to the WT strain in topical inoculation experiments. Additionally, loss of BbNoxB or BbNoxR impaired infection structures formation, penetration ability, ROS production, and actin aggregation during fungal infection. BbNoxs are crucial for fungal growth, development, and virulence in <i>B. bassiana</i>, playing essential roles in infection structures formation, penetration, ROS production, and actin assembly. Understanding their functions provides insights into <i>B. bassiana</i>’s pathogenic mechanisms.
DOI: 10.6084/m9.figshare.25807511
title: Genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 carbapenem-resistant <i>Klebsiella pneumoniae</i>

description: ST11 is the most common lineage among carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) infections in Asia. Diverse morphotypes resulting from genetic mutations are associated with significant differences in microbial characteristics among <i>K. pneumoniae</i> isolates. Here, we investigated the genetic determinants and critical characteristics associated with distinct morphotypes of ST11 CRKP. An ST11-KL47 CRKP isolate carrying a pLVPK-like virulence plasmid was isolated from a patient with a bloodstream infection; the isolate had the “mcsw” morphotype. Two distinct morphotypes (“ntrd” and “msdw”) were derived from this strain during <i>in vitro</i> passage. Whole genome sequencing was used to identify mutations that cause the distinct morphotypes of ST11 CRKP. Transmission electron microscopy, antimicrobial susceptibility tests, growth assays, biofilm formation, virulence assays, membrane permeability assays, and RNA-seq analysis were used to investigate the specific characteristics associated with different morphotypes of ST11 CRKP. Compared with the parental mcsw morphotype, the ntrd morphotype resulted from mutation of genes involved in capsular polysaccharide biosynthesis (<i>wza</i>, <i>wzc</i>, and <i>wbaP</i>), a result validated by gene knockout experiments. This morphotype showed capsule deficiency and lower virulence potential, but higher biofilm production. By contrast, the msdw morphotype displayed competition deficiency and increased susceptibility to chlorhexidine and polymyxin B. Further analyses indicated that these characteristics were caused by interruption of the sigma factor gene <i>rpoN</i> by insertion mutations and deletion of the <i>rpoN</i> gene, which attenuated membrane integrity presumably by downregulating the phage shock protein operon. These data expand current understanding of genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 CRKP.
DOI: 10.6084/m9.figshare.25807511.v1
title: Genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 carbapenem-resistant <i>Klebsiella pneumoniae</i>

description: ST11 is the most common lineage among carbapenem-resistant <i>Klebsiella pneumoniae</i> (CRKP) infections in Asia. Diverse morphotypes resulting from genetic mutations are associated with significant differences in microbial characteristics among <i>K. pneumoniae</i> isolates. Here, we investigated the genetic determinants and critical characteristics associated with distinct morphotypes of ST11 CRKP. An ST11-KL47 CRKP isolate carrying a pLVPK-like virulence plasmid was isolated from a patient with a bloodstream infection; the isolate had the “mcsw” morphotype. Two distinct morphotypes (“ntrd” and “msdw”) were derived from this strain during <i>in vitro</i> passage. Whole genome sequencing was used to identify mutations that cause the distinct morphotypes of ST11 CRKP. Transmission electron microscopy, antimicrobial susceptibility tests, growth assays, biofilm formation, virulence assays, membrane permeability assays, and RNA-seq analysis were used to investigate the specific characteristics associated with different morphotypes of ST11 CRKP. Compared with the parental mcsw morphotype, the ntrd morphotype resulted from mutation of genes involved in capsular polysaccharide biosynthesis (<i>wza</i>, <i>wzc</i>, and <i>wbaP</i>), a result validated by gene knockout experiments. This morphotype showed capsule deficiency and lower virulence potential, but higher biofilm production. By contrast, the msdw morphotype displayed competition deficiency and increased susceptibility to chlorhexidine and polymyxin B. Further analyses indicated that these characteristics were caused by interruption of the sigma factor gene <i>rpoN</i> by insertion mutations and deletion of the <i>rpoN</i> gene, which attenuated membrane integrity presumably by downregulating the phage shock protein operon. These data expand current understanding of genetic, virulence, and antimicrobial resistance characteristics associated with distinct morphotypes in ST11 CRKP.
DOI: 10.6084/m9.figshare.26410785
title: <i>LGG</i> promotes activation of intestinal ILC3 through TLR2 receptor and inhibits <i>salmonella typhimurium</i> infection in mice

description: <i>Salmonella</i> is a foodborne pathogen that causes disruption of intestinal mucosal immunity, leading to acute gastroenteritis in the host. In this study, we found that <i>Salmonella Typhimurium</i> (<i>STM</i>) infection of the intestinal tract of mice led to a significant increase in the proportion of <i>Lacticaseibacillus</i>, while the secretion of IL-22 from type 3 innate lymphoid cells (ILC3) increased significantly. Feeding <i>Lacticaseibacillus rhamnosus GG</i> (<i>LGG</i>) effectively alleviated the infection of <i>STM</i> in the mouse intestines. TLR2<sup>−/−</sup> mice experiments found that TLR2-expressing dendritic cells (DCs) are crucial for <i>LGG</i>‘s activation of ILC3. Subsequent in vitro experiments showed that heat-killed <i>LGG</i> (HK<i>-LGG</i>) could promote DCs to secrete IL-23, which in turn further promotes the activation of ILC3 and the secretion of IL-22. Finally, organoid experiments further verified that IL-22 secreted by ILC3 can enhance the intestinal mucosal immune barrier and inhibit <i>STM</i> infection. This study demonstrates that oral administration of <i>LGG</i> is a potential method for inhibiting <i>STM</i> infection.
DOI: 10.6084/m9.figshare.26410785.v1
title: <i>LGG</i> promotes activation of intestinal ILC3 through TLR2 receptor and inhibits <i>salmonella typhimurium</i> infection in mice

description: <i>Salmonella</i> is a foodborne pathogen that causes disruption of intestinal mucosal immunity, leading to acute gastroenteritis in the host. In this study, we found that <i>Salmonella Typhimurium</i> (<i>STM</i>) infection of the intestinal tract of mice led to a significant increase in the proportion of <i>Lacticaseibacillus</i>, while the secretion of IL-22 from type 3 innate lymphoid cells (ILC3) increased significantly. Feeding <i>Lacticaseibacillus rhamnosus GG</i> (<i>LGG</i>) effectively alleviated the infection of <i>STM</i> in the mouse intestines. TLR2<sup>−/−</sup> mice experiments found that TLR2-expressing dendritic cells (DCs) are crucial for <i>LGG</i>‘s activation of ILC3. Subsequent in vitro experiments showed that heat-killed <i>LGG</i> (HK<i>-LGG</i>) could promote DCs to secrete IL-23, which in turn further promotes the activation of ILC3 and the secretion of IL-22. Finally, organoid experiments further verified that IL-22 secreted by ILC3 can enhance the intestinal mucosal immune barrier and inhibit <i>STM</i> infection. This study demonstrates that oral administration of <i>LGG</i> is a potential method for inhibiting <i>STM</i> infection.
DOI: 10.6084/m9.figshare.27013028
title: Antifungal activities of Equol against <i>Candida albicans in vitro</i> and <i>in vivo</i>

description: <i>Candida albicans</i> is an opportunistic fungal pathogen that can cause systemic infections in immunocompromised individuals. Morphological transition and biofilm formation are major virulence factors of <i>C. albicans</i>. Moreover, biofilm enhances resistance to antifungal agents. Therefore, it is urgent to identify new and effective compounds to target the biofilm of <i>C. albicans</i>. In the present study, the antifungal activities of equol against <i>C. albicans</i> were investigated. <i>In vitro</i>, the microdilution analysis and spot assay result showed that equol exhibited potent inhibitory activities against <i>C. albicans</i>. Further investigations confirmed that the antifungal effects of equol involved interference with the transition from yeast to hypha and biofilm formation of <i>C. albicans</i>. In addition, transcriptome sequencing and reverse transcription-quantitative PCR (qRT-PCR) analysis showed that equol significantly downregulated the expression of several genes in the Ras1-cAMP-PKA pathway related to hyphae and biofilm formation and significantly upregulated the expression of the negative transcriptional repressors <i>RFG1</i> and <i>TUP1</i>. Moreover, equol effectively reduced the production of cAMP, a key messenger in the Ras1-cAMP-PKA pathway, while supplementation with cAMP partly rescued the equol-induced defects in hyphal development. Furthermore, in a mouse model of systemic candidiasis (SC), equol treatment significantly decreased the fungal burden (liver, kidneys, and lung) in mice and local tissue damage, while enhancing the production of interleukin-10 (IL-10). Together, these findings confirm that equol is a potentially effective agent for treatment of SC.
DOI: 10.6084/m9.figshare.27013028.v1
title: Antifungal activities of Equol against <i>Candida albicans in vitro</i> and <i>in vivo</i>

description: <i>Candida albicans</i> is an opportunistic fungal pathogen that can cause systemic infections in immunocompromised individuals. Morphological transition and biofilm formation are major virulence factors of <i>C. albicans</i>. Moreover, biofilm enhances resistance to antifungal agents. Therefore, it is urgent to identify new and effective compounds to target the biofilm of <i>C. albicans</i>. In the present study, the antifungal activities of equol against <i>C. albicans</i> were investigated. <i>In vitro</i>, the microdilution analysis and spot assay result showed that equol exhibited potent inhibitory activities against <i>C. albicans</i>. Further investigations confirmed that the antifungal effects of equol involved interference with the transition from yeast to hypha and biofilm formation of <i>C. albicans</i>. In addition, transcriptome sequencing and reverse transcription-quantitative PCR (qRT-PCR) analysis showed that equol significantly downregulated the expression of several genes in the Ras1-cAMP-PKA pathway related to hyphae and biofilm formation and significantly upregulated the expression of the negative transcriptional repressors <i>RFG1</i> and <i>TUP1</i>. Moreover, equol effectively reduced the production of cAMP, a key messenger in the Ras1-cAMP-PKA pathway, while supplementation with cAMP partly rescued the equol-induced defects in hyphal development. Furthermore, in a mouse model of systemic candidiasis (SC), equol treatment significantly decreased the fungal burden (liver, kidneys, and lung) in mice and local tissue damage, while enhancing the production of interleukin-10 (IL-10). Together, these findings confirm that equol is a potentially effective agent for treatment of SC.