cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.28646388.v1
title: Gut microbiome composition and metabolic activity in metabolic associated fatty liver disease

description: Metabolic Associated Fatty Liver Disease (MAFLD) impacts approximately 25% of the global population. The objective of our study was to elucidate the characteristics of the gut microbiome and alterations in plasma metabolites among MAFLD patients. Between April 2023 and July 2023, 60 patients with MAFLD, along with 60 age, ethnicity, and sex-matched healthy controls (HCs), were enrolled from Inner Mongolia Autonomous Region, China. Analysis of gut microbiota composition and plasma metabolic profiles was conducted using metagenome sequencing and LC-MS. LEfSe analysis identified five pivotal species: Eubacterium rectale, Dialister invisus, Pseudoruminococcus massiliensis, GGB3278 SGB4328, and Ruminococcaceae bacteria. In subgroup analysis, Eubacterium rectale tended to be increased by more than 2 times and more than double in the non-obese MAFLD group, and MAFLD with moderate hepatic steatosis（HS）respectively. Combinations of phenomics and metabolomics yielded the highest accuracy (AUC = 0.97) in the MAFLD diagnosis. Combinations of phenomics and metagenomics yielded the highest accuracy (AUC = 0.94) in the prediction of the MAFLD HS progress. Plasma samples identified 172 metabolites mainly composed of fatty acid metabolites such as propionic acid and butyric acid analogues. Ruminococcaceae bacteria have a strong positive correlation with β-Alanine, Uric acid and L-Valine. Pseudoruminococcus massiliensis have a strong positive correlation with β-Alanine. Increases in Eubacterium rectale and decreases in Dialister invisus seem to be indicative of MAFLD patients. Eubacterium rectale may predicts HS degree of MAFLD and play an important role in the development of non-obese MAFLD. Eubacterium rectale can generate more propionic acid and butyric acid analogues to absorb energy and increase lipid synthesis, and ultimately cause MAFLD. The observed association between Ruminococcaceae bacteria and β-Alanine or Uric acid in these patients could offer fresh insights into the disease mechanism.
DOI: 10.6084/m9.figshare.29859218
title: Construction and protective evaluation of a recombinant attenuated <i>Salmonella</i> vaccine delivering <i>Mycoplasma synoviae</i> antigens

description: <i>Mycoplasma synoviae</i> (<i>M. synoviae</i>) is a highly detrimental avian pathogen that has resulted in substantial economic losses within the global poultry industry. The existing vaccines, presently in use, fail to offer comprehensive protection. The objective of this study was to create recombinant attenuated <i>Salmonella</i> vaccine (RASV) strains, namely rSC0130(pS-rRS01790), rSC0130(pS-rBMP), rSC0130(pS-rGrpE), rSC0130(pS-rRS00900), and rSC0130(pS-rRS00275), expressing RS01790, BMP, GrpE, RS00900, and RS00275 proteins, and verify their protective effects. Assessed candidate vaccines for their growth characteristics, plasmid stability, and capability to synthesize exogenous antigens. The results demonstrated that the expression of exogenous antigens had no detrimental impact on the growth performance of the candidate vaccine strain. Additionally, the plasmid remained stable and continued to express through the 50th generation, confirming its long-term stability within the strain. Furthermore, all five antigens were successfully synthesized within the candidate vaccines. The immune protection results demonstrated that candidate vaccine immunization induced specific humoral, mucosal, and cellular immune responses. The growth performance of the rSC0130(pS-rRS01790), rSC0130(pS-rBMP), and rSC0130(pS-rGrpE) immunized groups exhibited significant recovery, and the air sac lesion scores were significantly lower than those of the challenge control group and the rSC0130(pS0018) control group. All candidate vaccines effectively reduced the colonization of <i>M. synoviae</i> in the pharynx and mitigated damage to the tracheal mucosa. These results underscore the potential of the RASV carrying the <i>M. synoviae</i> antigen as a promising approach for the development of vaccines against <i>M. synoviae</i> and suggest that RASV could serve as a novel strategy for prevention and control of <i>M. synoviae</i> infections.
DOI: 10.6084/m9.figshare.29859218.v2
title: Construction and protective evaluation of a recombinant attenuated <i>Salmonella</i> vaccine delivering <i>Mycoplasma synoviae</i> antigens

description: <i>Mycoplasma synoviae</i> (<i>M. synoviae</i>) is a highly detrimental avian pathogen that has resulted in substantial economic losses within the global poultry industry. The existing vaccines, presently in use, fail to offer comprehensive protection. The objective of this study was to create recombinant attenuated <i>Salmonella</i> vaccine (RASV) strains, namely rSC0130(pS-rRS01790), rSC0130(pS-rBMP), rSC0130(pS-rGrpE), rSC0130(pS-rRS00900), and rSC0130(pS-rRS00275), expressing RS01790, BMP, GrpE, RS00900, and RS00275 proteins, and verify their protective effects. Assessed candidate vaccines for their growth characteristics, plasmid stability, and capability to synthesize exogenous antigens. The results demonstrated that the expression of exogenous antigens had no detrimental impact on the growth performance of the candidate vaccine strain. Additionally, the plasmid remained stable and continued to express through the 50th generation, confirming its long-term stability within the strain. Furthermore, all five antigens were successfully synthesized within the candidate vaccines. The immune protection results demonstrated that candidate vaccine immunization induced specific humoral, mucosal, and cellular immune responses. The growth performance of the rSC0130(pS-rRS01790), rSC0130(pS-rBMP), and rSC0130(pS-rGrpE) immunized groups exhibited significant recovery, and the air sac lesion scores were significantly lower than those of the challenge control group and the rSC0130(pS0018) control group. All candidate vaccines effectively reduced the colonization of <i>M. synoviae</i> in the pharynx and mitigated damage to the tracheal mucosa. These results underscore the potential of the RASV carrying the <i>M. synoviae</i> antigen as a promising approach for the development of vaccines against <i>M. synoviae</i> and suggest that RASV could serve as a novel strategy for prevention and control of <i>M. synoviae</i> infections.
DOI: 10.6084/m9.figshare.29859218.v1
title: Construction and protective evaluation of a recombinant attenuated <i>salmonella</i> vaccine delivering <i>mycoplasma synoviae</i> antigens

description: <i>Mycoplasma synoviae</i> (<i>M. synoviae</i>) is a highly detrimental avian pathogen that has resulted in substantial economic losses within the global poultry industry. The existing vaccines, presently in use, fail to offer comprehensive protection. The objective of this study was to create recombinant attenuated <i>Salmonella</i> vaccine (RASV) strains, namely rSC0130(pS-rRS01790), rSC0130(pS-rBMP), rSC0130(pS-rGrpE), rSC0130(pS-rRS00900), and rSC0130(pS-rRS00275), expressing RS01790, BMP, GrpE, RS00900, and RS00275 proteins, and verify their protective effects. Assessed candidate vaccines for their growth characteristics, plasmid stability, and capability to synthesize exogenous antigens. The results demonstrated that the expression of exogenous antigens had no detrimental impact on the growth performance of the candidate vaccine strain. Additionally, the plasmid remained stable and continued to express through the 50th generation, confirming its long-term stability within the strain. Furthermore, all five antigens were successfully synthesized within the candidate vaccines. The immune protection results demonstrated that candidate vaccine immunization induced specific humoral, mucosal, and cellular immune responses. The growth performance of the rSC0130(pS-rRS01790), rSC0130(pS-rBMP), and rSC0130(pS-rGrpE) immunized groups exhibited significant recovery, and the air sac lesion scores were significantly lower than those of the challenge control group and the rSC0130(pS0018) control group. All candidate vaccines effectively reduced the colonization of <i>M. synoviae</i> in the pharynx and mitigated damage to the tracheal mucosa. These results underscore the potential of the RASV carrying the <i>M. synoviae</i> antigen as a promising approach for the development of vaccines against <i>M. synoviae</i> and suggest that RASV could serve as a novel strategy for prevention and control of <i>M. synoviae</i> infections.
DOI: 10.6084/m9.figshare.29117226
title: Comparative genomics of <i>Salmonella enterica</i> serovars Paratyphi A, Typhi and Typhimurium reveals distinct profiles of their pangenome, mobile genetic elements, antimicrobial resistance and defense systems repertoire

description: <i>Salmonella enterica</i> (<i>S. enterica</i>) is a highly ubiquitous and diverse animal and human pathogen. Distinct <i>S. enterica</i> serovars may present varying host-specificity and cause different diseases. While the human-restricted serovars <i>S</i>. Typhi (STY) and <i>S</i>. Paratyphi A (SPA) cause in humans a systemic life-threatening enteric fever, the host-generalist serovar, <i>S</i>. Typhimurium (STM) causes in immunocompetent individuals a self-limited gastroenteritis. Here, we have performed whole-genome sequencing and hybrid assembly of new SPA and STY typhoidal strains and took a comparative genomics approach to examine their phylogeny, pangenome structure and accessory genome content in comparison to the reference non-typhoidal serovar, STM. Our results identified previously uncharacterized lineages of SPA and refined the presence and distribution of core pseudogenes in typhoidal serovars. Pangenome analysis showed that while these serovars have a relatively similar core-genome size, the accessory genome of STM is more than four times larger than those of typhoidal Salmonellae and that STY and SPA display a more closed pangenome than STM. Unexpectedly, we demonstrate that STY and SPA present distinct differences in their pangenome composition, with a noticeable lower number of prophages, conjugative elements and antimicrobial genes per genome in SPA vs. STY. These results suggest that although SPA and STY are closely related at the DNA level, share a similar lifestyle and cause a symptomatic-indistinguishable disease, their genomic evolution and accessory genomes are markedly different. Moreover, these results may provide genomic explanation to phenotypic and epidemiological differences in antimicrobial resistance profiles associated with these serovars globally.
DOI: 10.6084/m9.figshare.29117226.v1
title: Comparative genomics of <i>Salmonella enterica</i> serovars Paratyphi A, Typhi and Typhimurium reveals distinct profiles of their pangenome, mobile genetic elements, antimicrobial resistance and defense systems repertoire

description: <i>Salmonella enterica</i> (<i>S. enterica</i>) is a highly ubiquitous and diverse animal and human pathogen. Distinct <i>S. enterica</i> serovars may present varying host-specificity and cause different diseases. While the human-restricted serovars <i>S</i>. Typhi (STY) and <i>S</i>. Paratyphi A (SPA) cause in humans a systemic life-threatening enteric fever, the host-generalist serovar, <i>S</i>. Typhimurium (STM) causes in immunocompetent individuals a self-limited gastroenteritis. Here, we have performed whole-genome sequencing and hybrid assembly of new SPA and STY typhoidal strains and took a comparative genomics approach to examine their phylogeny, pangenome structure and accessory genome content in comparison to the reference non-typhoidal serovar, STM. Our results identified previously uncharacterized lineages of SPA and refined the presence and distribution of core pseudogenes in typhoidal serovars. Pangenome analysis showed that while these serovars have a relatively similar core-genome size, the accessory genome of STM is more than four times larger than those of typhoidal Salmonellae and that STY and SPA display a more closed pangenome than STM. Unexpectedly, we demonstrate that STY and SPA present distinct differences in their pangenome composition, with a noticeable lower number of prophages, conjugative elements and antimicrobial genes per genome in SPA vs. STY. These results suggest that although SPA and STY are closely related at the DNA level, share a similar lifestyle and cause a symptomatic-indistinguishable disease, their genomic evolution and accessory genomes are markedly different. Moreover, these results may provide genomic explanation to phenotypic and epidemiological differences in antimicrobial resistance profiles associated with these serovars globally.
DOI: 10.6084/m9.figshare.29580357
title: IscR-tmRNA regulatory axis plays a key role in multiple stress response and pathogenicity in <i>Aeromonas veronii</i>

description: Bacterial pathogens intricately modulate their response to a variety of stress and the virulence, particularly in light of the dynamic conditions both in natural habitat and within host organisms. Transfer-messenger RNA (tmRNA), which plays an important role in pathogenicity due to its major function in the trans-translation system for ribosome rescue, has been proved as a stress response molecule. Herein, our results indicate that the global regulator IscR acts as a crucial activator responsible for the expression of tmRNA in <i>Aeromonas veronii</i>, a bacterial pathogen posing significant challenges to both aquatic industry and public health. Bacterial one-hybrid and electrophoretic mobility shift assays (EMSA) confirm the direct binding of IscR to the promoter region of the <i>ssrA</i> gene which encodes tmRNA. Moreover, our phenotypic characterizations illustrate that the complementation of tmRNA can rescue the defects of <i>iscR</i> deletion in response to adverse stress, including nutrient deprivation, elevated temperatures, β-lactam antibiotics, and oxidative stress, as well as in establishing the pathogenicity characterized by motility, aggregation, adhesion, cytotoxicity, bacterial competition, and colonization in mice. Our findings offer insights into a potential model for strengthening bacterial survival in external environments, and provide an initial glimpse into the intricate interplay between the functional roles of IscR and tmRNA in the pathogenicity through the IscR-tmRNA regulatory axis.
DOI: 10.6084/m9.figshare.29580357.v1
title: IscR-tmRNA regulatory axis plays a key role in multiple stress response and pathogenicity in <i>Aeromonas veronii</i>

description: Bacterial pathogens intricately modulate their response to a variety of stress and the virulence, particularly in light of the dynamic conditions both in natural habitat and within host organisms. Transfer-messenger RNA (tmRNA), which plays an important role in pathogenicity due to its major function in the trans-translation system for ribosome rescue, has been proved as a stress response molecule. Herein, our results indicate that the global regulator IscR acts as a crucial activator responsible for the expression of tmRNA in <i>Aeromonas veronii</i>, a bacterial pathogen posing significant challenges to both aquatic industry and public health. Bacterial one-hybrid and electrophoretic mobility shift assays (EMSA) confirm the direct binding of IscR to the promoter region of the <i>ssrA</i> gene which encodes tmRNA. Moreover, our phenotypic characterizations illustrate that the complementation of tmRNA can rescue the defects of <i>iscR</i> deletion in response to adverse stress, including nutrient deprivation, elevated temperatures, β-lactam antibiotics, and oxidative stress, as well as in establishing the pathogenicity characterized by motility, aggregation, adhesion, cytotoxicity, bacterial competition, and colonization in mice. Our findings offer insights into a potential model for strengthening bacterial survival in external environments, and provide an initial glimpse into the intricate interplay between the functional roles of IscR and tmRNA in the pathogenicity through the IscR-tmRNA regulatory axis.
DOI: 10.6084/m9.figshare.28233697
title: The sulfur-related metabolic status of <i>Aspergillus fumigatus</i> during infection reveals cytosolic serine hydroxymethyltransferase as a promising antifungal target

description: Sulfur metabolism is an essential aspect of fungal physiology and pathogenicity. Fungal sulfur metabolism comprises anabolic and catabolic routes that are not well conserved in mammals, therefore is considered a promising source of prospective novel antifungal targets. To gain insight into <i>Aspergillus fumigatus</i> sulfur-related metabolism during infection, we used a NanoString custom nCounter-TagSet and compared the expression of 68 key metabolic genes in different murine models of invasive pulmonary aspergillosis, at 3 time-points, and under a variety of <i>in vitro</i> conditions. We identified a set of 15 genes that were consistently expressed at higher levels <i>in vivo</i> than <i>in vitro</i>, suggesting that they may be particularly relevant for intrapulmonary growth and thus constitute promising drug targets. Indeed, the role of 5 of the 15 genes has previously been empirically validated, supporting the likelihood that the remaining candidates are relevant. In addition, the analysis of gene expression dynamics at early (16 h), mid (24 h), and late (72 h) time-points uncovered potential disease initiation and progression factors. We further characterized one of the identified genes, encoding the cytosolic serine hydroxymethyltransferase ShmB, and demonstrated that it is an essential gene of <i>A. fumigatus</i>, also required for virulence in a murine model of established pulmonary infection. We further showed that the structure of the ligand-binding pocket of the fungal enzyme differs significantly from its human counterpart, suggesting that specific inhibitors can be designed. Therefore, <i>in vivo</i> transcriptomics is a powerful tool for identifying genes crucial for fungal pathogenicity that may encode promising antifungal target candidates.
DOI: 10.6084/m9.figshare.28233697.v1
title: The sulfur-related metabolic status of <i>Aspergillus fumigatus</i> during infection reveals cytosolic serine hydroxymethyltransferase as a promising antifungal target

description: Sulfur metabolism is an essential aspect of fungal physiology and pathogenicity. Fungal sulfur metabolism comprises anabolic and catabolic routes that are not well conserved in mammals, therefore is considered a promising source of prospective novel antifungal targets. To gain insight into <i>Aspergillus fumigatus</i> sulfur-related metabolism during infection, we used a NanoString custom nCounter-TagSet and compared the expression of 68 key metabolic genes in different murine models of invasive pulmonary aspergillosis, at 3 time-points, and under a variety of <i>in vitro</i> conditions. We identified a set of 15 genes that were consistently expressed at higher levels <i>in vivo</i> than <i>in vitro</i>, suggesting that they may be particularly relevant for intrapulmonary growth and thus constitute promising drug targets. Indeed, the role of 5 of the 15 genes has previously been empirically validated, supporting the likelihood that the remaining candidates are relevant. In addition, the analysis of gene expression dynamics at early (16 h), mid (24 h), and late (72 h) time-points uncovered potential disease initiation and progression factors. We further characterized one of the identified genes, encoding the cytosolic serine hydroxymethyltransferase ShmB, and demonstrated that it is an essential gene of <i>A. fumigatus</i>, also required for virulence in a murine model of established pulmonary infection. We further showed that the structure of the ligand-binding pocket of the fungal enzyme differs significantly from its human counterpart, suggesting that specific inhibitors can be designed. Therefore, <i>in vivo</i> transcriptomics is a powerful tool for identifying genes crucial for fungal pathogenicity that may encode promising antifungal target candidates.
DOI: 10.6084/m9.figshare.29041332
title: A small RNA from <i>Streptococcus suis</i> epidemic ST7 strain promotes bacterial survival in host blood and brain by enhancing oxidative stress resistance

description: <i>Streptococcus suis</i> is a Gram-positive pathogen causing septicaemia and meningitis in pigs and humans. However, how <i>S. suis</i> maintains a high bacterial load in the blood and brain is poorly understood. In this study, we found that a small RNA rss03 is predominantly present in <i>S. suis</i>, <i>Streptococcus parasuis</i>, and <i>Streptococcus ruminantium</i>, implying a conserved biological function. rss03 with a size of 303 nt mainly exists in <i>S. suis</i> sequence type (ST) 1 and epidemic ST7 strains that are responsible for human infections in China. Using MS2-affinity purification coupled with RNA sequencing (MAPS), proteomics analysis, and CopraRNA prediction, 14 direct targets of rss03 from an ST7 strain were identified. These direct targets mainly involve substance transport, transcriptional regulation, rRNA modification, and stress response. A more detailed analysis reveals that rss03 interacts with the coding region of <i>glpF</i> mRNA, and unexpectedly rss03 protects <i>glpF</i> mRNA from degradation by RNase J1. The GlpF protein is an aquaporin, contributes to <i>S. suis</i> oxidative stress resistance by H<sub>2</sub>O<sub>2</sub> efflux, and facilitates bacterial survival in murine macrophages RAW264.7. Finally, we showed that rss03 and GlpF are required to maintain a high bacterial load in mouse blood and brain. Our study presents the first sRNA targetome in streptococci, enriches the knowledge of sRNA regulation in streptococci, and identifies pathways contributing to <i>S. suis</i> pathogenesis.
DOI: 10.6084/m9.figshare.29041332.v1
title: A small RNA from <i>Streptococcus suis</i> epidemic ST7 strain promotes bacterial survival in host blood and brain by enhancing oxidative stress resistance

description: <i>Streptococcus suis</i> is a Gram-positive pathogen causing septicaemia and meningitis in pigs and humans. However, how <i>S. suis</i> maintains a high bacterial load in the blood and brain is poorly understood. In this study, we found that a small RNA rss03 is predominantly present in <i>S. suis</i>, <i>Streptococcus parasuis</i>, and <i>Streptococcus ruminantium</i>, implying a conserved biological function. rss03 with a size of 303 nt mainly exists in <i>S. suis</i> sequence type (ST) 1 and epidemic ST7 strains that are responsible for human infections in China. Using MS2-affinity purification coupled with RNA sequencing (MAPS), proteomics analysis, and CopraRNA prediction, 14 direct targets of rss03 from an ST7 strain were identified. These direct targets mainly involve substance transport, transcriptional regulation, rRNA modification, and stress response. A more detailed analysis reveals that rss03 interacts with the coding region of <i>glpF</i> mRNA, and unexpectedly rss03 protects <i>glpF</i> mRNA from degradation by RNase J1. The GlpF protein is an aquaporin, contributes to <i>S. suis</i> oxidative stress resistance by H<sub>2</sub>O<sub>2</sub> efflux, and facilitates bacterial survival in murine macrophages RAW264.7. Finally, we showed that rss03 and GlpF are required to maintain a high bacterial load in mouse blood and brain. Our study presents the first sRNA targetome in streptococci, enriches the knowledge of sRNA regulation in streptococci, and identifies pathways contributing to <i>S. suis</i> pathogenesis.