cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.29582156.v1
title: Dietary iron attenuates <i>Clostridioides difficile</i> infection via modulation of intestinal immune response and gut microbiota

description: <i>Clostridioides difficile</i> (<i>C. difficile</i>) is one of the majors causes of antibiotic-associated diarrhea globally. Host vulnerability to <i>C. difficile</i> infection (CDI) is largely affected by gut microbiota, which in turn is influenced by diet. However, the mechanism underlying the interplay between diet and the gut microbiota that regulates host susceptibility to CDI remains unclear. This study aimed to investigate how a high-iron diet affects the intestinal immune response, microbiota, and metabolism in mice infected with <i>C. difficile</i>. We explored the specific role of the unique gut microbiota and metabolites on CDI. A mouse model of CDI was constructed with or without high dietary iron treatment. The effect of high iron levels on gut microbiota was analyzed by 16S rRNA gene sequencing, and the role of gut microbiota was confirmed by fecal microbiota transplantation (FMT). High dietary iron (400 mg/kg ferrous sulfate) alleviated CDI by decreasing <i>C. difficile</i> pathogenicity and altering host intestinal neutrophil recruitment. Furthermore, <i>E. coli AVS0501</i>, enriched in the gut microbiota of iron-treated CDI mice, showed prophylactic and therapeutic effects on CDI. Moreover, the production of L-proline and tauroursodeoxycholic acid (TUDCA) in CDI mice treated with high dietary iron influenced <i>C. difficile</i> colonization, toxin production, and in turn, regulates the intestinal neutrophil response. Thus, high dietary iron alleviates <i>C. difficile</i> induced enteritis by regulating gut microbiota maintaining gut homeostasis, suggesting that high dietary iron may be an important determinant of disease control.
DOI: 10.6084/m9.figshare.30007340.v1
title: The ABC type fucose operon regulated by XtrSs through CcpA contributes to <i>streptococcus suis</i> survival in macrophages

description: <i>Streptococcus suis</i> (<i>S. suis</i>), an important zoonotic pathogen, poses a huge threat to the pig industry and human health. The fucose operon (FCS) is found in many bacteria that utilize host glycosylation modifications, contributing to bacterial growth and infection. We previously discovered that the virulence associated streptococcal transcriptional regulator XtrSs could downregulate FCS transcription. In this study, the FCSs of <i>S. suis</i> were classified into ABC and PTS types, and XtrSs indirectly repressed ABC type FCS transcription. Importantly, we found that Catabolite control protein A (CcpA) was the intermediate regulator of XtrSs, but not the FCS upstream regulator FcsR, directly repressing ABC type FCS transcription by binding to a novel Cre site. Interestingly, although ABC type FCS responded to fucose, <i>S. suis</i> failed to proliferate in media with fucose as the sole carbon source. Notably, FCS mutant treated macrophages exhibited decreased fucosyltransferases transcription and impaired AMPK/mTOR signaling to a certain extent, which resulted in increased autophagy processes and ultimately decreasing <i>S. suis</i> survival in macrophages. In conclusion, our findings first confirmed the detailed regulatory mechanism of ABC type FCS and revealed that FCS contributed to the intramacrophage survival of <i>S. suis</i> by inhibiting autophagy processes.
DOI: 10.6084/m9.figshare.29582156
title: Dietary iron attenuates <i>Clostridioides difficile</i> infection via modulation of intestinal immune response and gut microbiota

description: <i>Clostridioides difficile</i> (<i>C. difficile</i>) is one of the majors causes of antibiotic-associated diarrhea globally. Host vulnerability to <i>C. difficile</i> infection (CDI) is largely affected by gut microbiota, which in turn is influenced by diet. However, the mechanism underlying the interplay between diet and the gut microbiota that regulates host susceptibility to CDI remains unclear. This study aimed to investigate how a high-iron diet affects the intestinal immune response, microbiota, and metabolism in mice infected with <i>C. difficile</i>. We explored the specific role of the unique gut microbiota and metabolites on CDI. A mouse model of CDI was constructed with or without high dietary iron treatment. The effect of high iron levels on gut microbiota was analyzed by 16S rRNA gene sequencing, and the role of gut microbiota was confirmed by fecal microbiota transplantation (FMT). High dietary iron (400 mg/kg ferrous sulfate) alleviated CDI by decreasing <i>C. difficile</i> pathogenicity and altering host intestinal neutrophil recruitment. Furthermore, <i>E. coli AVS0501</i>, enriched in the gut microbiota of iron-treated CDI mice, showed prophylactic and therapeutic effects on CDI. Moreover, the production of L-proline and tauroursodeoxycholic acid (TUDCA) in CDI mice treated with high dietary iron influenced <i>C. difficile</i> colonization, toxin production, and in turn, regulates the intestinal neutrophil response. Thus, high dietary iron alleviates <i>C. difficile</i> induced enteritis by regulating gut microbiota maintaining gut homeostasis, suggesting that high dietary iron may be an important determinant of disease control.
DOI: 10.6084/m9.figshare.29658897
title: Fumarate and nitrate reduction regulator (FNR) modulates hypermucoviscosity and virulence in hypervirulent <i>Klebsiella pneumoniae</i> through anaerobic adaptation

description: Hypervirulent <i>Klebsiella pneumoniae</i> (hvKP), a pathogen responsible for severe invasive infections, exhibits a hypermucoviscosity (HMV) phenotype that is closely associated with its virulence. While fumarate and nitrate reduction regulator (FNR), a global transcription regulator, is critical for bacterial adaptation to hypoxic conditions, its role in hvKP pathogenicity remains unexplored. This study demonstrates that FNR modulates the HMV phenotype and virulence of the hvKP strain NTUH-K2044 under anaerobic conditions. Through targeted deletion and complementation of the <i>fnr</i> gene, combined with phenotypic, molecular, cellular, and animal infection assays, we show that FNR positively regulates the HMV phenotype. Notably, this regulation is independent of several genes previously implicated in HMV formation, including <i>rmpA</i>, <i>rmpA2</i>, <i>wzy-K1</i> (<i>magA</i>), <i>rmpC</i>, and <i>rmpD</i>. In the absence of <i>fnr</i>, the HMV phenotype was abolished, while the transcript levels of these genes increased significantly, suggesting a compensatory or indirect regulatory mechanism that warrants further investigation. Functionally, FNR-mediated HMV enhanced bacterial resistance to phagocytosis and serum killing while suppressing host colonization features such as fimbriae formation, biofilm production, and epithelial cell adhesion. In animal infection models, FNR also contributed positively to hvKP virulence. These findings highlight the role of FNR in regulating the HMV phenotype and virulence in hvKP, facilitating host adaptation and immune evasion. Targeting FNR may thus represent a promising strategy for the development of novel therapeutics.
DOI: 10.6084/m9.figshare.29658897.v1
title: Fumarate and nitrate reduction regulator (FNR) modulates hypermucoviscosity and virulence in hypervirulent <i>Klebsiella pneumoniae</i> through anaerobic adaptation

description: Hypervirulent <i>Klebsiella pneumoniae</i> (hvKP), a pathogen responsible for severe invasive infections, exhibits a hypermucoviscosity (HMV) phenotype that is closely associated with its virulence. While fumarate and nitrate reduction regulator (FNR), a global transcription regulator, is critical for bacterial adaptation to hypoxic conditions, its role in hvKP pathogenicity remains unexplored. This study demonstrates that FNR modulates the HMV phenotype and virulence of the hvKP strain NTUH-K2044 under anaerobic conditions. Through targeted deletion and complementation of the <i>fnr</i> gene, combined with phenotypic, molecular, cellular, and animal infection assays, we show that FNR positively regulates the HMV phenotype. Notably, this regulation is independent of several genes previously implicated in HMV formation, including <i>rmpA</i>, <i>rmpA2</i>, <i>wzy-K1</i> (<i>magA</i>), <i>rmpC</i>, and <i>rmpD</i>. In the absence of <i>fnr</i>, the HMV phenotype was abolished, while the transcript levels of these genes increased significantly, suggesting a compensatory or indirect regulatory mechanism that warrants further investigation. Functionally, FNR-mediated HMV enhanced bacterial resistance to phagocytosis and serum killing while suppressing host colonization features such as fimbriae formation, biofilm production, and epithelial cell adhesion. In animal infection models, FNR also contributed positively to hvKP virulence. These findings highlight the role of FNR in regulating the HMV phenotype and virulence in hvKP, facilitating host adaptation and immune evasion. Targeting FNR may thus represent a promising strategy for the development of novel therapeutics.
DOI: 10.6084/m9.figshare.29041341
title: <i>Burkholderia cenocepacia</i> and <i>Pseudomonas aeruginosa</i> in dual-species models: Insights into population distribution, antibiotic susceptibility, and virulence

description: Multispecies biofilms are communities composed of different microorganisms embedded in an auto-synthesized polymeric matrix. <i>Pseudomonas aeruginosa</i> and <i>Burkholderia cenocepacia</i> are two multidrug-resistant and biofilm-forming opportunistic pathogens often found in the lungs of people living with cystic fibrosis. In this context, planktonic, static, and dynamic biofilms and <i>in vivo</i> models of both species were optimized in this work to understand their population dynamics, disposition, virulence, and antibiotic susceptibility. From the coculture models optimized in this work, we determined that <i>B. cenocepacia</i> grows in a clustered, aggregative manner at the bottom layers of biofilms, in close contact with <i>P. aeruginosa</i>, that tends to occupy the top layers. Their coexistence increases virulence-related gene expression in both species at early stages of coinfection and in <i>in vivo</i> models, while there was a general downregulation of virulence-related genes after longer coexistence periods as they eventually reach a non-competitive stage during chronic infections. When evaluating antimicrobial susceptibility, a decrease of antimicrobial tolerance was observed in both species when co-cultured. These findings shed light on the differential behavior of <i>P. aeruginosa</i> and <i>B. cenocepacia</i> in dual-species systems, stressing the relevance of multispecies studies in the clinical context.
DOI: 10.6084/m9.figshare.29041341.v1
title: <i>Burkholderia cenocepacia</i> and <i>Pseudomonas aeruginosa</i> in dual-species models: Insights into population distribution, antibiotic susceptibility, and virulence

description: Multispecies biofilms are communities composed of different microorganisms embedded in an auto-synthesized polymeric matrix. <i>Pseudomonas aeruginosa</i> and <i>Burkholderia cenocepacia</i> are two multidrug-resistant and biofilm-forming opportunistic pathogens often found in the lungs of people living with cystic fibrosis. In this context, planktonic, static, and dynamic biofilms and <i>in vivo</i> models of both species were optimized in this work to understand their population dynamics, disposition, virulence, and antibiotic susceptibility. From the coculture models optimized in this work, we determined that <i>B. cenocepacia</i> grows in a clustered, aggregative manner at the bottom layers of biofilms, in close contact with <i>P. aeruginosa</i>, that tends to occupy the top layers. Their coexistence increases virulence-related gene expression in both species at early stages of coinfection and in <i>in vivo</i> models, while there was a general downregulation of virulence-related genes after longer coexistence periods as they eventually reach a non-competitive stage during chronic infections. When evaluating antimicrobial susceptibility, a decrease of antimicrobial tolerance was observed in both species when co-cultured. These findings shed light on the differential behavior of <i>P. aeruginosa</i> and <i>B. cenocepacia</i> in dual-species systems, stressing the relevance of multispecies studies in the clinical context.
DOI: 10.6084/m9.figshare.30305386
title: Manganese homeostasis modulates glucan and chitin unmasking in the opportunistic yeast <i>Candida albicans</i>

description: <i>Candida albicans</i> is a commensal fungus and also the most prevalent human fungal pathogen. The ability of this opportunistic yeast to acquire and maintain homeostatic levels of manganese (Mn), particularly in the metal-limited host environment, is an important determinant of its fitness. Recent studies have underscored the importance of Mn acquisition through members of Smf transporters, in <i>C. albicans</i> virulence and its ability to withstand various stresses. In the present study, we undertook transcriptional profiling in the mutant of the Mn transporter Smf12 under restricted Mn availability to identify processes that are directly impacted by impaired Mn uptake. Our analysis revealed that <i>smf12</i> displayed a transcriptional pattern suggestive of a cell wall defect, with many transcripts associated with cell wall biogenesis being differentially regulated. <i>smf12</i> together with <i>smf11</i>, a mutant of the closest homolog of Smf12, exhibited hypersensitivity to cell wall stressors and an altered cell wall ultrastructure. The <i>smf</i> mutants also exhibited unmasking of both β-glucan and chitin, which unexpectedly resulted in a decreased rate of phagocytosis by macrophages, suggesting impaired recognition or internalization. Furthermore, we showed that Mn-mediated unmasking of β-glucan required modulation of glucanase activity and was not mediated through the calcineurin pathway. This study uncovers a novel role for Mn in maintaining cell wall integrity and modulating the exposure of fungal antigenic determinants, further emphasizing the critical role of this metal in supporting the opportunistic nature of <i>C. albicans</i>.
DOI: 10.6084/m9.figshare.30305386.v1
title: Manganese homeostasis modulates glucan and chitin unmasking in the opportunistic yeast <i>Candida albicans</i>

description: <i>Candida albicans</i> is a commensal fungus and also the most prevalent human fungal pathogen. The ability of this opportunistic yeast to acquire and maintain homeostatic levels of manganese (Mn), particularly in the metal-limited host environment, is an important determinant of its fitness. Recent studies have underscored the importance of Mn acquisition through members of Smf transporters, in <i>C. albicans</i> virulence and its ability to withstand various stresses. In the present study, we undertook transcriptional profiling in the mutant of the Mn transporter Smf12 under restricted Mn availability to identify processes that are directly impacted by impaired Mn uptake. Our analysis revealed that <i>smf12</i> displayed a transcriptional pattern suggestive of a cell wall defect, with many transcripts associated with cell wall biogenesis being differentially regulated. <i>smf12</i> together with <i>smf11</i>, a mutant of the closest homolog of Smf12, exhibited hypersensitivity to cell wall stressors and an altered cell wall ultrastructure. The <i>smf</i> mutants also exhibited unmasking of both β-glucan and chitin, which unexpectedly resulted in a decreased rate of phagocytosis by macrophages, suggesting impaired recognition or internalization. Furthermore, we showed that Mn-mediated unmasking of β-glucan required modulation of glucanase activity and was not mediated through the calcineurin pathway. This study uncovers a novel role for Mn in maintaining cell wall integrity and modulating the exposure of fungal antigenic determinants, further emphasizing the critical role of this metal in supporting the opportunistic nature of <i>C. albicans</i>.
DOI: 10.6084/m9.figshare.29988556
title: The first discovery of the group IV GETV from Pangolin, China

description: We confirmed novel Group IV Getah virus (GETV) was detected from pangolin, which is the first discovered new host. And this is the first discovery of Group IV GETV in Guangxi province, China. This strain, named CHIKV-China/GX2020, is highly homologous to the 2017 Thailand strain. Bayesian analysis shows that GETV has a faster evolutionary rate with 3.487 (2.213–4.771) × 10<sup>−4</sup> substitutions/site/year. The Lollipop plot demonstrated in detail the amino acid differences between the isolated strain and the other sequences of GETV of Group IV and revealed that more mutations occur in the structural protein E2. Compared with the 2017 Thailand isolate, GETV-China/GX2020 has been discovered important amino acid mutation of E2-H207N. This mutation results in a change in the conformation of the E2 protein, which may in turn affect the infectivity or pathogenicity of the virus. Existing surveillance programs and diagnostics efficiency of potential outbreaks of GETV need strengthen.
DOI: 10.6084/m9.figshare.29988556.v1
title: The first discovery of the group IV GETV from Pangolin, China

description: We confirmed novel Group IV Getah virus (GETV) was detected from pangolin, which is the first discovered new host. And this is the first discovery of Group IV GETV in Guangxi province, China. This strain, named CHIKV-China/GX2020, is highly homologous to the 2017 Thailand strain. Bayesian analysis shows that GETV has a faster evolutionary rate with 3.487 (2.213–4.771) × 10<sup>−4</sup> substitutions/site/year. The Lollipop plot demonstrated in detail the amino acid differences between the isolated strain and the other sequences of GETV of Group IV and revealed that more mutations occur in the structural protein E2. Compared with the 2017 Thailand isolate, GETV-China/GX2020 has been discovered important amino acid mutation of E2-H207N. This mutation results in a change in the conformation of the E2 protein, which may in turn affect the infectivity or pathogenicity of the virus. Existing surveillance programs and diagnostics efficiency of potential outbreaks of GETV need strengthen.
DOI: 10.6084/m9.figshare.30128120
title: The global regulator SpoVG modulates <i>Staphylococcus aureus</i> virulence through Agr-dependent pathways

description: <i>Staphylococcus aureus</i> (<i>S. aureus</i>) is a major pathogen responsible for a wide range of infections in both community and healthcare settings. Its virulence is orchestrated by a complex regulatory network. SpoVG, a global regulator in <i>S. aureus</i>, has been shown to play crucial roles in antibiotic tolerance, stress adaptation, and biofilm formation. However, its specific role in virulence regulation has remained poorly understood. Here, we investigated the role of SpoVG in the modulation of <i>S. aureus</i> virulence. The results demonstrate that deletion of <i>spoVG</i> significantly increased the hemolytic activity and virulence of the SA3 strain, as evidenced by both in vitro assays and murine infection models. Transcriptomic profiling and RT – qPCR analyses revealed that the inactivation of <i>spoVG</i> activated the Agr quorum-sensing system, resulting in upregulating key virulence genes, including <i>psmα</i>, <i>psmβ</i>, <i>hla</i>, and <i>hlg</i>. Further, β-galactosidase reporter assays and electrophoretic mobility shift assays (EMSA) confirmed that SpoVG directly binds to the promoter regions of <i>agrACDB</i>, <i>psmα</i>, and <i>psmβ</i>, thereby repressing their transcription. Collectively, these findings identify SpoVG as a critical negative regulator of virulence in <i>S. aureus</i>, acting through direct repression of the Agr system and its downstream effectors. This study provides new mechanistic insights into SpoVG-mediated virulence regulation and highlights SpoVG as a potential target for anti-virulence strategies against <i>S. aureus</i> infections.
DOI: 10.6084/m9.figshare.30128120.v2
title: The global regulator SpoVG modulates <i>Staphylococcus aureus</i> virulence through Agr-dependent pathways

description: <i>Staphylococcus aureus</i> (<i>S. aureus</i>) is a major pathogen responsible for a wide range of infections in both community and healthcare settings. Its virulence is orchestrated by a complex regulatory network. SpoVG, a global regulator in <i>S. aureus</i>, has been shown to play crucial roles in antibiotic tolerance, stress adaptation, and biofilm formation. However, its specific role in virulence regulation has remained poorly understood. Here, we investigated the role of SpoVG in the modulation of <i>S. aureus</i> virulence. The results demonstrate that deletion of <i>spoVG</i> significantly increased the hemolytic activity and virulence of the SA3 strain, as evidenced by both in vitro assays and murine infection models. Transcriptomic profiling and RT – qPCR analyses revealed that the inactivation of <i>spoVG</i> activated the Agr quorum-sensing system, resulting in upregulating key virulence genes, including <i>psmα</i>, <i>psmβ</i>, <i>hla</i>, and <i>hlg</i>. Further, β-galactosidase reporter assays and electrophoretic mobility shift assays (EMSA) confirmed that SpoVG directly binds to the promoter regions of <i>agrACDB</i>, <i>psmα</i>, and <i>psmβ</i>, thereby repressing their transcription. Collectively, these findings identify SpoVG as a critical negative regulator of virulence in <i>S. aureus</i>, acting through direct repression of the Agr system and its downstream effectors. This study provides new mechanistic insights into SpoVG-mediated virulence regulation and highlights SpoVG as a potential target for anti-virulence strategies against <i>S. aureus</i> infections.
DOI: 10.6084/m9.figshare.29358814
title: Mitochondrial anchor protein Num11 is key to pathogenicity of <i>Candida albicans</i> by affecting mitochondrial function and cell wall masking

description: The mitochondrial anchoring protein Num1 directly affects mitochondrial redox function, cell division, and growth in unicellular fungi. However, the functional characterization of Num11, its <i>Candida albicans</i> homolog, remains elusive. Our investigation revealed that Num11 deletion in <i>C. albicans</i> caused profound cellular defects: (1) Disrupted cell cycle progression and mitochondrial dysfunction manifesting as mitochondrial morphological aggregation, ATP depletion, membrane potential collapse, and ROS overproduction; (2) Hypersensitivity to cell wall-perturbing agents accompanied by thicker cell walls and increased surface exposure of β-glucan/chitin; (3) Enhanced macrophage phagocytosis and proinflammatory cytokine release. These cellular alterations translated to significantly attenuated virulence in both <i>Galleria mellonella</i> and systematic mice infection models. Mechanistically, transcriptome profiling and protein interaction analyses demonstrated Num11 deficiency hyperactivates the Cdc42-Cek1 MAPK cascade (phospho-Cek1 increased), driving cell wall remodeling. Our findings establish Num11’s dual closely connected regulatory roles in <i>C. albicans</i> pathogenesis: as a mitochondrial scaffold maintaining bioenergetic homeostasis to attenuate growth and as a negative regulator of the Cdc42-Cek1 axis controlling cell wall architecture through affection on mitochondria. These coordinated actions collectively underscore Num11’s critical role in mediating host–pathogen interactions during invasive candidiasis.