Genome-Wide Identification of Conditionally Essential Genes Supporting Streptococcus suis Growth in Serum and Cerebrospinal Fluid
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB89170 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| ERR14954103.fastq.gz | Fastqsanger.gz | |||
| ERR14994925.fastq.gz | Fastqsanger.gz | |||
| ERR14994926.fastq.gz | Fastqsanger.gz | |||
| ERR14951772.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 11 |
Similar Datasets
Project description:Streptococcus suis is a Gram-positive bacterium and zoonotic pathogen that causes meningitis and sepsis in pigs and humans. The aim of this study was to identify genes required for S. suis infection. We created Tn-Seq libraries in a virulent S. suis strain 10, which was used to inoculate pigs in an intrathecal experimental infection. Comparative analysis of the relative abundance of mutants recovered from different sites of infection (blood, cerebrospinal fluid, and meninges of the brain) identified 361 conditionally essential genes, i.e. required for infection, which is about 18% of the genome. The conditionally essential genes were primarily involved in metabolic and transport processes, regulation, ribosomal structure and biogenesis, transcription, and cell wall membrane and envelope biogenesis, stress defenses, and immune evasion. Directed mutants were created in a set of 10 genes of different genetic ontologies and their role was determined in ex vivo models. Mutants showed different levels of sensitivity to survival in whole blood, serum, cerebrospinal fluid, thermic shock, and stress conditions, as compared to the wild type. Additionally, the role of three selected mutants was validated in co-infection experiments in which pigs were infected with both wild type and isogenic mutant strains. The genetic determinants of infection identified in this work contribute to novel insights in S. suis pathogenesis and could serve as targets for novel vaccines or antimicrobial drugs.
| S-EPMC7239030 | biostudies-literature
Project description:Streptococcus suis (SS) is an important pathogen of pigs, and it is also recognized as a zoonotic agent for humans. SS infection may result in septicemia or meningitis in the host. However, little is known about genes that contribute to the virulence process and survival within host blood or cerebrospinal fluid (CSF). Small RNAs (sRNA) have emerged as key regulators of virulence in several bacteria, but they have not been investigated in SS. Here, using a differential RNA-sequencing approach and RNAs from SS strain P1/7 grown in rich medium, pig blood, or CSF, we present the SS genome-wide map of 793 transcriptional start sites and 370 operons. In addition to identifying 29 sRNAs, we show that five sRNA deletion mutants attenuate SS virulence in a zebrafish infection model. Homology searches revealed that 10 sRNAs were predicted to be present in other pathogenic Streptococcus species. Compared with wild-type strain P1/7, sRNAs rss03, rss05, and rss06 deletion mutants were significantly more sensitive to killing by pig blood. It is possible that rss06 contributes to SS virulence by indirectly activating expression of SSU0308, a virulence gene encoding a zinc-binding lipoprotein. In blood, genes involved in the synthesis of capsular polysaccharide (CPS) and subversion of host defenses were up-regulated. In contrast, in CSF, genes for CPS synthesis were down-regulated. Our study is the first analysis of SS sRNAs involved in virulence and has both improved our understanding of SS pathogenesis and increased the number of sRNAs known to play definitive roles in bacterial virulence.
| S-EPMC4024642 | biostudies-literature
Project description:Streptococcus suis is a globally emerging zoonotic pathogen that can cause invasive disease commonly associated with meningitis in pigs and humans. To cause meningitis, S. suis must invade the central nervous system (CNS) by crossing the neurovascular unit, also known as the blood-brain barrier (BBB), or vascularized choroid plexus (ChP) epithelium known as the blood-cerebrospinal fluid barrier (BCSFB). Recently developed ChP organoids have been shown to accurately replicate the cytoarchitecture and physiological functions of the ChP epithelium in vivo. Here, we used human induced pluripotent stem cells (iPSC)-derived ChP organoids as an in vitro model to investigate S. suis interaction and infection at the BCSFB. Our study revealed that S. suis is capable of translocating across the epithelium of ChP organoids without causing significant cell death or compromising the barrier integrity. Plasminogen (Plg) binding to S. suis in the presence of tissue plasminogen activator (tPA), which converts immobilized Plg to plasmin (Pln), significantly increased the basolateral to apical translocation across ChP organoids into the CSF-like fluid in the lumen. S. suis was able to replicate at the same rate in CSF and laboratory S. suis culture medium but reached a lower final density. The analysis of transcriptomes in ChP organoids after S. suis infection indicated inflammatory responses, while the addition of Plg further suggested extracellular matrix (ECM) remodeling. To our knowledge, this is the first study using ChP organoids to investigate bacterial infection of the BCSFB. Our findings highlight the potential of ChP organoids as a valuable tool for studying the mechanisms of bacterial interaction and infection of the human ChP in vitro.
| S-EPMC11812244 | biostudies-literature
Project description:Streptococcus suis is a zoonotic pathogen that can cause severe pathologies such as septicemia and meningitis in its natural porcine host as well as in humans. Establishment of disease requires not only virulence of the infecting strain but also an appropriate metabolic activity of the pathogen in its host environment. However, it is yet largely unknown how the streptococcal metabolism adapts to the different host niches encountered during infection. Our previous isotopologue profiling studies on S. suis grown in porcine blood and cerebrospinal fluid (CSF) revealed conserved activities of central carbon metabolism in both body fluids. On the other hand, they suggested differences in the de novo amino acid biosynthesis. This prompted us to further dissect S. suis adaptation to porcine blood and CSF by RNA deep sequencing (RNA-seq). In blood, the majority of differentially expressed genes were associated with transport of alternative carbohydrate sources and the carbohydrate metabolism (pentose phosphate pathway, glycogen metabolism). In CSF, predominantly genes involved in the biosynthesis of branched-chain and aromatic amino acids were differentially expressed. Especially, isoleucine biosynthesis seems to be of major importance for S. suis in CSF because several related biosynthetic genes were more highly expressed. In conclusion, our data revealed niche-specific metabolic gene activity which emphasizes a selective adaptation of S. suis to host environments.
| S-EPMC5371895 | biostudies-literature
Project description:A protein microarray kit (QAR-INF-1-2, RayBiotech Life Inc., Norcross, GA, USA) was used to detect 10 kinds of inflammatory factors in the CSF and serum (nN=5 per group), including IFN-γ, IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-13, MCP-1, and TNF-α.
2023-04-03 | GSE228521 | GEO
Project description:BackgroundMultiple sclerosis (MS) is a chronic debilitating disorder characterized by persisting damage to the brain caused by autoreactive leukocytes. Leukocyte activation is regulated by cytokines, which are readily detected in MS serum and cerebrospinal fluid (CSF).ObjectiveSerum and CSF levels of forty-five cytokines were analyzed to identify MS diagnostic markers.MethodsCytokines were analyzed using multiplex immunoassay. ANOVA-based feature and Pearson correlation coefficient scores were calculated to select the features which were used as input by machine learning models, to predict and classify MS.ResultsTwenty-two and twenty cytokines were altered in CSF and serum, respectively. The MS diagnosis accuracy was ≥92% when any randomly selected five of these biomarkers were used. Interestingly, the highest accuracy (99%) of MS diagnosis was demonstrated when CCL27, IFN-γ, and IL-4 were part of the five selected cytokines, suggesting their important role in MS pathogenesis. Also, these binary classifier models had the accuracy in the range of 70-78% (serum) and 60-69% (CSF) to discriminate between the progressive (primary and secondary progressive) and relapsing-remitting forms of MS.ConclusionWe identified the set of cytokines from the serum and CSF that could be used for the MS diagnosis and classification.
| S-EPMC7607285 | biostudies-literature
Project description:BackgroundSyringomyelia is a spinal cord cavity containing cerebrospinal fluid (CSF)-like fluid. If syringomyelia asymmetrically involves the dorsal horn grey matter of the spinal cord, affected dogs show increased signs of dysesthesia and neuropathic pain, like increased itching behaviour. In the dorsal horn, amongst others, receptors for Interleukin-31 (IL-31) can be found. IL-31 is one of the main cytokines involved in the pathogenesis of pruritus in atopic dermatitis in different species. This study investigates suspected elevated levels of IL-31 in serum and CSF of dogs showing signs of pain or increased itching behaviour related to syringomyelia. The IL-31 were measured in archived samples (52 serum and 35 CSF samples) of dogs with syringomyelia (n = 48), atopic dermatitis (n = 3) and of healthy control dogs (n = 11) using a competitive canine IL-31 ELISA.ResultsMean serum IL-31 level in dogs with syringomyelia was 150.1 pg/ml (n = 39), in dogs with atopic dermatitis 228.3 pg/ml (n = 3) and in healthy dogs 80.7 pg/ml (n = 10). Mean CSF IL-31 value was 146.3 pg/ml (n = 27) in dogs with syringomyelia and 186.2 pg/ml (n = 8) in healthy dogs. Individual patients with syringomyelia (especially dogs with otitis media or otitis media and interna or intervertebral disc herniation) showed high IL-31 levels in serum and CSF samples, but the difference was not statistically significant. IL-31 serum and CSF levels did not differ significantly in dogs with syringomyelia with or without itching behaviour and with or without signs of pain.ConclusionBased on this study, increased IL-31 levels seem not to be correlated with itching behaviour or signs of pain in dogs with syringomyelia, but might be caused by other underlying diseases.
| S-EPMC10666301 | biostudies-literature
Project description:The development of non-invasive diagnostic methods is crucial in early disease detection and thus better treatment options. Small RNAs have been identified as good candidates for such diagnostic markers due to their small size, which allows ease of transport from live cells. Correlating small RNAs in bodily fluid with those in tissue cells of interest may even shed light on disease mechanisms and the development of therapeutic targets. tRNA-derived RNA fragments (tRFs), a family of recently discovered small non-coding RNAs (sncRNAs), have been found to be significantly changed in various disease states, including Alzheimer's disease (AD), the most common type of dementia. Previously, tRFs have been found to be significantly enhanced in human AD hippocampus tissues. However, whether tRFs change in body fluids is unknown. In this study, we planned to identify baselines for potential usage of tRFs as biomarkers in cerebrospinal fluid and blood serum for future development of AD biomarkers. Towards this goal, we used T4 polynucleotide kinase-RNA-seq, a modified next-generation sequencing technique, to identify detectable tRFs in human cerebrospinal fluid (CSF) and serum samples. Interestingly, we found an abundance of tRFs in both CSF and serum samples in comparison to microRNAs, well-known small RNAs (about 3-10 times higher in read counts). This clearly indicates the significant potential of tRFs as non-invasive biomarkers in CSF and serum.
2023-12-01 | GSE241686 | GEO
Project description:Streptococcus suis is a zoonotic pathogen that can invade the central nervous system (CNS) and cause meningitis in pigs and humans. The vascularized choroid plexus (ChP) epithelium, known as the blood-cerebrospinal fluid barrier (BCSFB), serves as a route for S. suis invasion of the CNS. In this study, we aimed to use human induced pluripotent stem cells (iPSC)-derived ChP organoids as an in vitro model to investigate S. suis interaction and infection at the BCSFB and the responses of ChP organoids to S. suis using transcriptomics. We also investigated whether the known plasminogen (Plg) binding to S. suis surface enolase and its conversion to proteolytic plasmin (Pln) would facilitate S. suis translocation across the ChP organoid epithelium and alter the ChP response to infection.
2025-02-13 | E-MTAB-14229 | biostudies-arrayexpress