cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.28936059
title: A promising endeavor against human cytomegalovirus: Predominant epitopes-based recombinant subunit vaccine RH<i>Ec</i><sup>IE1/pp65/pp150</sup>

description: Human cytomegalovirus (HCMV) is widespread in the population, typically remaining latent. However, it can cause severe morbidity and mortality in transplant patients and immunodeficient individuals. Currently, there is no approved vaccine against HCMV. This study used immunoinformatics methods to predict the predominant T and B-cell epitopes of three key HCMV proteins, including phosphoprotein 65 (pp65), pp150, and immediate-early protein 1 (IE1). Subsequently, we synthesized a recombinant subunit vaccine (RH<i>Ec</i><sup>IE1/pp65/pp150</sup>) from <i>Escherichia coli</i>, comprising RH<i>Ec</i>-1 and RH<i>Ec</i>-2. We observed that the RH<i>Ec</i><sup>IE1/pp65/pp150</sup> vaccine exhibited high safety and immunogenicity in mice, enhancing a significant upregulation of CD80, CD86, CD40, and MHCII on dendritic cells and macrophages. Additionally, the vaccine activated innate immune responses through the NF-κB signalling pathway, triggering CD4<sup>+</sup> and CD8<sup>+</sup>T cells to secrete tumour necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2, directing the T-cell response towards Th1. Moreover, it stimulated CD4<sup>+</sup>T cells to secrete IL-4, IL-6, and IL-10, promoting B-cell immunity. Furthermore, the RH<i>Ec</i><sup>IE1/pp65/pp150</sup> vaccine induced the formation of abundant memory cells and high levels of neutralizing antibody titres, conducive to providing long-lasting protection. Taken together, the RH<i>Ec</i><sup>IE1/pp65/pp150</sup> vaccine is a promising endeavour against HCMV, and these findings contribute valuable insights to the development of HCMV vaccine candidates.
DOI: 10.6084/m9.figshare.28936059.v1
title: A promising endeavor against human cytomegalovirus: Predominant epitopes-based recombinant subunit vaccine RH<i>Ec</i><sup>IE1/pp65/pp150</sup>

description: Human cytomegalovirus (HCMV) is widespread in the population, typically remaining latent. However, it can cause severe morbidity and mortality in transplant patients and immunodeficient individuals. Currently, there is no approved vaccine against HCMV. This study used immunoinformatics methods to predict the predominant T and B-cell epitopes of three key HCMV proteins, including phosphoprotein 65 (pp65), pp150, and immediate-early protein 1 (IE1). Subsequently, we synthesized a recombinant subunit vaccine (RH<i>Ec</i><sup>IE1/pp65/pp150</sup>) from <i>Escherichia coli</i>, comprising RH<i>Ec</i>-1 and RH<i>Ec</i>-2. We observed that the RH<i>Ec</i><sup>IE1/pp65/pp150</sup> vaccine exhibited high safety and immunogenicity in mice, enhancing a significant upregulation of CD80, CD86, CD40, and MHCII on dendritic cells and macrophages. Additionally, the vaccine activated innate immune responses through the NF-κB signalling pathway, triggering CD4<sup>+</sup> and CD8<sup>+</sup>T cells to secrete tumour necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2, directing the T-cell response towards Th1. Moreover, it stimulated CD4<sup>+</sup>T cells to secrete IL-4, IL-6, and IL-10, promoting B-cell immunity. Furthermore, the RH<i>Ec</i><sup>IE1/pp65/pp150</sup> vaccine induced the formation of abundant memory cells and high levels of neutralizing antibody titres, conducive to providing long-lasting protection. Taken together, the RH<i>Ec</i><sup>IE1/pp65/pp150</sup> vaccine is a promising endeavour against HCMV, and these findings contribute valuable insights to the development of HCMV vaccine candidates.
DOI: 10.6084/m9.figshare.29975803
title: Virulence factors are preserved within carbapenem-resistant <i>Acinetobacter baumannii</i> clades

description: Carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) is an important threat to hospitalized patients. The virulence of <i>A. baumannii</i> varies between strains and geographic locations, which is believed to be related to its genetic plasticity. A comprehensive evaluation of virulence factor (VF) content of CRAB across genetically related clones is lacking. Therefore, we aimed to determine the evolution of VFs among 246 CRAB isolates belonging to major STs, ST2 and ST3. We used WGS to assess 136 VFs and found that 110 VFs were present in most isolates (49 VFs were universally present, 61 were ubiquitous) and 25 occurred sporadically. The distribution of the 25 sporadic VF genes was homogenous in ST3 but heterogeneous in ST2. Within ST2, we found high intra-clade homogeneity and high inter-clade heterogeneity of VFs. The homogeneity of VF content in ST2 clades and its uniformity in ST3 suggest a distant evolutionary segregation of VFs at the root of ST/clade divergence. VF content reflects remote events resulting in minimal variation between isolates belonging to the same ST/clade. Thus, the alleged differences in virulence of CRAB strains between geographical locations reflect differences in clonal distribution.
DOI: 10.6084/m9.figshare.29975803.v1
title: Virulence factors are preserved within carbapenem-resistant <i>Acinetobacter baumannii</i> clades

description: Carbapenem-resistant <i>Acinetobacter baumannii</i> (CRAB) is an important threat to hospitalized patients. The virulence of <i>A. baumannii</i> varies between strains and geographic locations, which is believed to be related to its genetic plasticity. A comprehensive evaluation of virulence factor (VF) content of CRAB across genetically related clones is lacking. Therefore, we aimed to determine the evolution of VFs among 246 CRAB isolates belonging to major STs, ST2 and ST3. We used WGS to assess 136 VFs and found that 110 VFs were present in most isolates (49 VFs were universally present, 61 were ubiquitous) and 25 occurred sporadically. The distribution of the 25 sporadic VF genes was homogenous in ST3 but heterogeneous in ST2. Within ST2, we found high intra-clade homogeneity and high inter-clade heterogeneity of VFs. The homogeneity of VF content in ST2 clades and its uniformity in ST3 suggest a distant evolutionary segregation of VFs at the root of ST/clade divergence. VF content reflects remote events resulting in minimal variation between isolates belonging to the same ST/clade. Thus, the alleged differences in virulence of CRAB strains between geographical locations reflect differences in clonal distribution.
DOI: 10.6084/m9.figshare.30042044
title: The putative AraC-type transcriptional regulator STM1082 facilitates <i>Salmonella</i> pathogenicity through modulation of intestinal invasion and intracellular replication

description: <i>Salmonella</i> is a food-borne zoonotic pathogen that causes human gastroenteritis and potentially fatal systemic infections. The invasion of intestinal epithelial cells and the survival and replication within host macrophages are essential for the intestinal and systemic infections caused by <i>Salmonella</i>, respectively. To precisely regulate the expression of virulence-related genes, <i>Salmonella</i> relies on a series of regulatory proteins. In this study, we identified STM1082, a putative AraC-type transcriptional regulator, as a new virulence activator in <i>Salmonella</i>. The expression of the <i>STM1082</i> gene is up-regulated when <i>Salmonella</i> invades HeLa epithelial cells and replicates within RAW264.7 macrophages. Mutation of <i>STM1082</i> impaired the ability of <i>Salmonella</i> to invade HeLa cells and replicate in RAW264.7 cells, and reduced its colonization in the mouse intestine, liver, and spleen. These results suggest that STM1082 facilitates <i>Salmonella</i> pathogenicity by promoting both its intestinal and systemic infections. Moreover, under intestinal-mimicking conditions, STM1082 increased the expression of genes related to 1,2-propanediol and ethanolamine metabolism, which are linked to <i>Salmonella</i>‘s intestinal survival. Under macrophage-mimicking conditions, it upregulated genes involved in purine biosynthesis, associated with <i>Salmonella</i>‘s systemic virulence. Together, these findings highlight the significant role of STM1082 in modulating the pathogenic mechanisms of <i>Salmonella</i>.
DOI: 10.6084/m9.figshare.30042044.v1
title: The putative AraC-type transcriptional regulator STM1082 facilitates <i>Salmonella</i> pathogenicity through modulation of intestinal invasion and intracellular replication

description: <i>Salmonella</i> is a food-borne zoonotic pathogen that causes human gastroenteritis and potentially fatal systemic infections. The invasion of intestinal epithelial cells and the survival and replication within host macrophages are essential for the intestinal and systemic infections caused by <i>Salmonella</i>, respectively. To precisely regulate the expression of virulence-related genes, <i>Salmonella</i> relies on a series of regulatory proteins. In this study, we identified STM1082, a putative AraC-type transcriptional regulator, as a new virulence activator in <i>Salmonella</i>. The expression of the <i>STM1082</i> gene is up-regulated when <i>Salmonella</i> invades HeLa epithelial cells and replicates within RAW264.7 macrophages. Mutation of <i>STM1082</i> impaired the ability of <i>Salmonella</i> to invade HeLa cells and replicate in RAW264.7 cells, and reduced its colonization in the mouse intestine, liver, and spleen. These results suggest that STM1082 facilitates <i>Salmonella</i> pathogenicity by promoting both its intestinal and systemic infections. Moreover, under intestinal-mimicking conditions, STM1082 increased the expression of genes related to 1,2-propanediol and ethanolamine metabolism, which are linked to <i>Salmonella</i>‘s intestinal survival. Under macrophage-mimicking conditions, it upregulated genes involved in purine biosynthesis, associated with <i>Salmonella</i>‘s systemic virulence. Together, these findings highlight the significant role of STM1082 in modulating the pathogenic mechanisms of <i>Salmonella</i>.
DOI: 10.6084/m9.figshare.30231312.v1
title: Recurrence following invasive GAS infections in adults: Triumph of virulence or failure of immunity?

description: Since late 2022, an increase in <i>Streptococcus pyogenes</i> (Group A <i>Streptococcus</i>, GAS) infections, both non-invasive and invasive (iGAS), has been reported globally. This study investigates iGAS cases complicated by recurrent infection (rGAS). From January to September 2023, four adults with severe iGAS suffered from rGAS. Clinical and whole-genome sequencing data were analysed. All patients required ICU admission and surgical debridement during their initial iGAS. The median interval between the initial iGAS and rGAS was 25.5 days, with a median duration of antibiotic treatment of 25 and 17.5 days, respectively. Patients A (female, age 69) and B (male, age 46) had upper limb necrotising fasciitis complicated by a subsequent cellulitis at the exact location. GAS <i>emm</i>1.3 (M1<sub>UK</sub>) was isolated in both patients, but patient A´s isolates carried a type-IV secretion system (T4SS), and this patient had a more severe course of infection. Patient C (male, age 66) had two episodes of bacteremia caused by GAS <i>emm</i>89.0 carrying T4SS and GAS <i>emm</i>12.37 with a frameshift in the <i>rocA</i> gene. Patient D (female, age 69) had upper limb cellulitis with bacteremia during the initial iGAS and upper limb cellulitis with septic gonitis as two concurrent manifestations of rGAS. All three isolates were identical, belonging to <i>emm</i>12.0 and carrying a 79 amino acid deletion in the SclA. Patients B and C had a reduced function of the complement lectin pathway and CD19+ lymphocyte deficiency. A combination of strain virulence factors and host immune deficiencies may predispose patients with iGAS to recurrence.
DOI: 10.6084/m9.figshare.30145340
title: Analyzing the distribution of virulence factors of <i>Mycobacterium tuberculosis</i> and the impact of virulence gene mutations on treatment outcomes in different lineages using whole-genome sequencing in Urumqi

description: This study centers on Urumqi, utilizing whole-genome sequencing and comparative genomics, we explored virulence factor mutations in different <i>Mycobacterium tuberculosis</i> lineages and their impact on tuberculosis patient prognosis. We utilized routine national drug resistance surveillance data from Urumqi, gathering demographic, epidemiological, and clinical data of patients with tuberculosis between 1 January 2017 to 31 December 2021. Whole-genome sequencing was employed, followed by bioinformatics analysis using various methods and statistical models. A total of 457 patients with tuberculosis were analyzed. Through whole-genome sequencing and bioinformatics analysis, we categorized these strains into three lineages: Lineage2 (347), Lineage3 (37), and Lineage4 (73), identifying 71 virulence factor mutations. The mutation rates of virulence factors in <i>M. tuberculosis</i> exhibited polarization. Significant differences in virulence factor mutation rates were observed among different <i>M. tuberculosis</i> lineages (all <i>p</i> values  &lt; 0.05). Additionally, mutations in espE, fadE29, and mbtI genes among Lineage2 patients were considered as risk factors influencing treatment outcomes (all <i>p</i> values &lt; 0.05), with odds ratios of 13.6200 (1.7285–107.3201), 7.1262 (1.3294–38.1997), and 14.8340 (1.1577–190.0784), respectively. Varied virulence factor mutations and virulence factor-related gene mutations exist across different <i>M. tuberculosis</i> lineages. Mutations in the espE, fadE29, and mbtI genes are risk factors that significantly affect the treatment outcome of Lineage2 patients. This finding serves as a reference for investigating the future evolutionary direction, transmissibility, drug resistance, and pathogenicity of <i>M. tuberculosis</i> virulence factors in regions with diverse lineages and frequent population movements.
DOI: 10.6084/m9.figshare.30145340.v1
title: Analyzing the distribution of virulence factors of <i>Mycobacterium tuberculosis</i> and the impact of virulence gene mutations on treatment outcomes in different lineages using whole-genome sequencing in Urumqi

description: This study centers on Urumqi, utilizing whole-genome sequencing and comparative genomics, we explored virulence factor mutations in different <i>Mycobacterium tuberculosis</i> lineages and their impact on tuberculosis patient prognosis. We utilized routine national drug resistance surveillance data from Urumqi, gathering demographic, epidemiological, and clinical data of patients with tuberculosis between 1 January 2017 to 31 December 2021. Whole-genome sequencing was employed, followed by bioinformatics analysis using various methods and statistical models. A total of 457 patients with tuberculosis were analyzed. Through whole-genome sequencing and bioinformatics analysis, we categorized these strains into three lineages: Lineage2 (347), Lineage3 (37), and Lineage4 (73), identifying 71 virulence factor mutations. The mutation rates of virulence factors in <i>M. tuberculosis</i> exhibited polarization. Significant differences in virulence factor mutation rates were observed among different <i>M. tuberculosis</i> lineages (all <i>p</i> values  &lt; 0.05). Additionally, mutations in espE, fadE29, and mbtI genes among Lineage2 patients were considered as risk factors influencing treatment outcomes (all <i>p</i> values &lt; 0.05), with odds ratios of 13.6200 (1.7285–107.3201), 7.1262 (1.3294–38.1997), and 14.8340 (1.1577–190.0784), respectively. Varied virulence factor mutations and virulence factor-related gene mutations exist across different <i>M. tuberculosis</i> lineages. Mutations in the espE, fadE29, and mbtI genes are risk factors that significantly affect the treatment outcome of Lineage2 patients. This finding serves as a reference for investigating the future evolutionary direction, transmissibility, drug resistance, and pathogenicity of <i>M. tuberculosis</i> virulence factors in regions with diverse lineages and frequent population movements.
DOI: 10.6084/m9.figshare.30231312
title: Recurrence following invasive GAS infections in adults: Triumph of virulence or failure of immunity?

description: Since late 2022, an increase in <i>Streptococcus pyogenes</i> (Group A <i>Streptococcus</i>, GAS) infections, both non-invasive and invasive (iGAS), has been reported globally. This study investigates iGAS cases complicated by recurrent infection (rGAS). From January to September 2023, four adults with severe iGAS suffered from rGAS. Clinical and whole-genome sequencing data were analysed. All patients required ICU admission and surgical debridement during their initial iGAS. The median interval between the initial iGAS and rGAS was 25.5 days, with a median duration of antibiotic treatment of 25 and 17.5 days, respectively. Patients A (female, age 69) and B (male, age 46) had upper limb necrotising fasciitis complicated by a subsequent cellulitis at the exact location. GAS <i>emm</i>1.3 (M1<sub>UK</sub>) was isolated in both patients, but patient A´s isolates carried a type-IV secretion system (T4SS), and this patient had a more severe course of infection. Patient C (male, age 66) had two episodes of bacteremia caused by GAS <i>emm</i>89.0 carrying T4SS and GAS <i>emm</i>12.37 with a frameshift in the <i>rocA</i> gene. Patient D (female, age 69) had upper limb cellulitis with bacteremia during the initial iGAS and upper limb cellulitis with septic gonitis as two concurrent manifestations of rGAS. All three isolates were identical, belonging to <i>emm</i>12.0 and carrying a 79 amino acid deletion in the SclA. Patients B and C had a reduced function of the complement lectin pathway and CD19+ lymphocyte deficiency. A combination of strain virulence factors and host immune deficiencies may predispose patients with iGAS to recurrence.
DOI: 10.6084/m9.figshare.30463572
title: Mechanisms of <i>Talaromyces marneffei</i> induced CNS injury: Synergistic roles of tauopathy, pyroptosis, and microglial inflammation

description: <i>Talaromyces marneffei</i> (<i>T. marneffei</i>) is an opportunistic, dimorphic fungus that has been clinically reported to involve the central nervous system (CNS). However, its neuroinvasive capacity and the underlying pathogenic mechanisms remain poorly understood. In this study, <i>T. marneffei</i> infection was found to impair learning, memory, and motor balance in mice, as demonstrated by Morris water maze and accelerating rotarod assays. Viable <i>T. marneffei</i> was subsequently isolated from hippocampus and cortex through fungal cultures, confirming its ability to invade the CNS. Histopathological analysis revealed CNS damage following infection, characterized by neuronal pyknosis, neurofibrillary tangles, and an increased presence of glial cells in the cortex. To investigate the underlying mechanisms, transcriptomic profiling showed significant enrichment of neurodegeneration pathways, with elevated Tau and GSDMD expression in hippocampal and cortical regions as well as N2a cells. Additionally, neuronal damage was exacerbated by indirect neurotoxicity mediated by microglial M1 polarization, accompanied by increased levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). In conclusion, our findings uncover for the first time a dual-pathogenic mechanism by which <i>T. marneffei</i> induces CNS injury: direct neuronal damage via Tau pathology and GSDMD-dependent pyroptosis and indirect inflammation-mediated injury via M1-polarized microglia. These insights not only advance our understanding of fungal neuroinvasion but also provide a foundation for the development of targeted therapies.
DOI: 10.6084/m9.figshare.30463572.v1
title: Mechanisms of <i>Talaromyces marneffei</i> induced CNS injury: Synergistic roles of tauopathy, pyroptosis, and microglial inflammation

description: <i>Talaromyces marneffei</i> (<i>T. marneffei</i>) is an opportunistic, dimorphic fungus that has been clinically reported to involve the central nervous system (CNS). However, its neuroinvasive capacity and the underlying pathogenic mechanisms remain poorly understood. In this study, <i>T. marneffei</i> infection was found to impair learning, memory, and motor balance in mice, as demonstrated by Morris water maze and accelerating rotarod assays. Viable <i>T. marneffei</i> was subsequently isolated from hippocampus and cortex through fungal cultures, confirming its ability to invade the CNS. Histopathological analysis revealed CNS damage following infection, characterized by neuronal pyknosis, neurofibrillary tangles, and an increased presence of glial cells in the cortex. To investigate the underlying mechanisms, transcriptomic profiling showed significant enrichment of neurodegeneration pathways, with elevated Tau and GSDMD expression in hippocampal and cortical regions as well as N2a cells. Additionally, neuronal damage was exacerbated by indirect neurotoxicity mediated by microglial M1 polarization, accompanied by increased levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). In conclusion, our findings uncover for the first time a dual-pathogenic mechanism by which <i>T. marneffei</i> induces CNS injury: direct neuronal damage via Tau pathology and GSDMD-dependent pyroptosis and indirect inflammation-mediated injury via M1-polarized microglia. These insights not only advance our understanding of fungal neuroinvasion but also provide a foundation for the development of targeted therapies.
DOI: 10.6084/m9.figshare.29126897
title: Genetic evolution and alterations in pathogenicity of highly pathogenic porcine reproductive and respiratory syndrome virus

description: Highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) and HP-PRRSV variant strains remain prevalent in China and Southeast Asian countries. However, their epidemiological aspects, genomic characteristics, relationships with vaccine strains, and changes in pathogenicity remain unclear. In this study, 2509 global L8.7 ORF5 sequences were utilized for analysis, we classified L8.7 into 7 groups (L8.7.1-L8.7.7). L8.7.1-L8.7.3 strains corresponded to previously reported classical PRRSVs, intermediate strains, and HP-PRRSVs, respectively, whereas L8.7.4-L8.7.7 were designated HP-like PRRSVs. Statistical analysis revealed that HP-like PRRSVs were the most prevalent among L8.7 strains, and L8.7.5 and L8.7.6 strains accounted for the highest proportions in recent years. A comprehensive analysis of the genome revealed that the majority (72.15%) of L8.7 strains presented a wild-type phenotype. Evolution rate analysis revealed that the evolution rate of L8.7.3-L8.7.7 PRRSV in China was reduced by about 4.1 times after the use of HP-PRRSV MLV. Pathogenicity test results indicate that in comparison with HP-PRRSV (L8.7.3: HuN4), the HP-like PRRSV strains (L8.7.5: DLF; L8.7.6: DLW) presented reduced pathogenicity in piglets while maintaining relatively high virulence. In summary, this study systematically elucidated the epidemiological dynamics, evolutionary trends, relationships with vaccine strains, and changes in pathogenicity associated with L8.7 strains, providing crucial data to support prevention and control strategies against L8.7 PRRSV.