Ontology highlight
ABSTRACT:
PROVIDER: PRJNA768849 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR16212000_1.fastq.gz | Fastqsanger.gz | |||
| SRR16212000_2.fastq.gz | Fastqsanger.gz | |||
| SRR16212001_1.fastq.gz | Fastqsanger.gz | |||
| SRR16212001_2.fastq.gz | Fastqsanger.gz | |||
| SRR16212002_1.fastq.gz | Fastqsanger.gz |
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Project description:A refined, controlled 16S rRNA gene sequencing approach reveals limited detection of cerebrospinal fluid microbiota in children with bacterial meningitis
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Project description:Cerebrospinal fluid transcriptional profiles in children with tuberculous meningitis (TBM) or other infections were compared using RNA-Seq and a biomarker signature driven by NMDA-receptor activation was identified
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Project description:Background: Meningitis can be caused by several viruses and bacteria. Identifying the causative pathogen as quickly as possible is crucial to initiate the most optimal therapy, as acute bacterial meningitis is associated with a significant morbidity and mortality. Bacterial meningitis requires antibiotics, as opposed to enteroviral meningitis, which only requires supportive therapy. Clinical presentation is usually not sufficient to differentiate between viral and bacterial meningitis, thereby necessitating cerebrospinal fluid (CSF) analysis by PCR and/or time-consuming bacterial cultures. However, collecting CSF in children is not always feasible and a rather invasive procedure. Methods: In 12 Belgian hospitals, we obtained acute blood samples from children with signs of meningitis (49 viral and 7 bacterial cases). (aged between 3 months and 16 years). After pathogen confirmation on CSF, the patient was asked to give a convalescent sample after recovery. 3’mRNA sequencing was performed to determine differentially expressed genes (DEGs) to create a host transcriptomic profile. Results: Enteroviral meningitis cases displayed the largest upregulated fold change enrichment in type I interferon production, response and signaling pathways. Patients with bacterial meningitis showed a significant upregulation of genes related to macrophage and neutrophil activation. We found several significantly DEGs between enteroviral and bacterial meningitis. Random forest classification showed that we were able to differentiate enteroviral from bacterial meningitis with an AUC of 0.982 on held-out samples. Conclusions: Enteroviral meningitis has an innate immunity signature with type 1 interferons as key players. Our classifier, based on blood host transcriptomic profiles of different meningitis cases, is a possible strong alternative for diagnosing enteroviral meningitis.
2019-06-27 | GSE133378 | GEO
Project description:Meningitis is a complex disease which can be caused by infection with either viral or bacterial pathogens. Viral meningitis is usually a sterile self-limiting disease with a good clinical prognosis, while bacterial meningitis is a potentially more serious disease with a higher mortality rate. Early diagnosis of bacterial meningitis is of paramount importance, as intervention with antimicrobial therapy increases the likelihood of a favourable clinical outcome. Routine diagnosis in many laboratories is still dependent to some degree on traditional methods e.g. culture, though molecular methods have been developed which can give a shorter time to diagnosis. However, there is not as yet a single test format that can detect all bacterial pathogens capable of causing meningitis. In addition, many tests e.g. real-time PCR have a finite limit for multiplexing and do not provide additional information such as strain or serogroup which is useful during outbreaks and for retrospective epidemiological surveillance. To this end we have developed a microarray probe set for detection of meningitis-associated bacterial pathogens including those in the N. meningitidis serogroups. Here we demonstrate utility of this array in specific detection of represented bacterial species and strains and in detection of pathogen signals in cerebrospinal fluid samples from patients with suspected bacterial meningitis. This method shows promise for development as a diagnostic tool; however, we discuss the technical issues encountered and suggest mechanisms to improve resolution of pathogen-specific signals in complex clinical samples.
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Project description:Meningitis is a complex disease which can be caused by infection with either viral or bacterial pathogens. Viral meningitis is usually a sterile self-limiting disease with a good clinical prognosis, while bacterial meningitis is a potentially more serious disease with a higher mortality rate. Early diagnosis of bacterial meningitis is of paramount importance, as intervention with antimicrobial therapy increases the likelihood of a favourable clinical outcome. Routine diagnosis in many laboratories is still dependent to some degree on traditional methods e.g. culture, though molecular methods have been developed which can give a shorter time to diagnosis. However, there is not as yet a single test format that can detect all bacterial pathogens capable of causing meningitis. In addition, many tests e.g. real-time PCR have a finite limit for multiplexing and do not provide additional information such as strain or serogroup which is useful during outbreaks and for retrospective epidemiological surveillance. To this end we have developed a microarray probe set for detection of meningitis-associated bacterial pathogens including those in the N. meningitidis serogroups. Here we demonstrate utility of this array in specific detection of represented bacterial species and strains and in detection of pathogen signals in cerebrospinal fluid samples from patients with suspected bacterial meningitis. This method shows promise for development as a diagnostic tool; however, we discuss the technical issues encountered and suggest mechanisms to improve resolution of pathogen-specific signals in complex clinical samples. We designed as part of a larger pan-pathogen microarray a sub-set of probes to meningitis-associated bacterial pathogens. We present here data confirming the pathogen-specificity of many of these probes and their potential use in clinical diagnosis through testing on a small number of patient clinical samples using human DNA and no added nucleic acid controls. These data are from single channel Cy3-labelled nucleic acids. Four technical replicates for each feature are included on the array.
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Project description:Neutrophils are crucial mediators of host defense and are recruited to the central nervous system in large numbers during acute bacterial meningitis caused by S. pneumoniae. Neutrophils can release neutrophil extracellular traps (NETs) during infections to trap and kill bacteria. Intact NETs are fibrous structures and mainly consist of decondensed DNA and neutrophil-derived antimicrobial proteins. We report the extensive presence of NETs in the cerebrospinal fluid of patients with pneumococcal meningitis, and absence of NETs in other forms of meningitis caused by viruses, Borrelia and subarachnoid hemorrhage. In a rat model of meningitis, a clinical strain of pneumococci induced NET formation in the cerebrospinal fluid. Importantly, disrupting NETs using DNase I significantly reduced bacterial load, demonstrating that NETs contribute to the pathogenesis of pneumococcal meningitis in vivo. Targeting NETs using DNase may represent a novel indication for an already approved drug as a non-antibiotic therapeutic option to treat acute pneumococcal meningitis.
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Project description:Bacterial meningitis is usually fatal without treatment. Prompt and accurate diagnosis coupled with the timely administration of parenteral antibiotics is necessary in order to save lives. We used label-free mass spectrometry based quantitative proteomics to identify specific protein signatures in cerebrospinal fluid from Malawian children with Streptococcus pneumoniae infection, the leading cause of bacterial meningitis in children, elderly and people infected with Human Immunodeficiency Virus. Samples were analysed in two independent cohorts (cases and controls, n=12 for the discovery cohort and n=16 for the verification cohort). The protein profiles clearly discriminated cases and controls. Proteins involved in the immune response and exosome cell signaling were significantly enriched in the infected samples. Several S. pneumoniae membrane proteins were identified suggesting these as potential therapeutic targets. For both cohorts, over 200 human proteins were up and down-regulated in children with confirmed S. pneumoniae infection in comparison with controls. Compiling proteins up- and down- regulated in both discovery and verification cohorts, we generated a comprehensive list of over 140 proteins from which diagnostic biomarkers could be nominated. For a panel of five selected proteins (cathelicidin, ceruloplasmin, myeloperoxidase, cystatin C and protein S100A8/S100 A9), we additionally verified the label-free results by automated quantitative western blot immunoassays (Simple Western™), with excellent agreement between the two experimental approaches. The proteins identified in our study could form the basis of development of a biomarker panel for rapid diagnosis. Our results could lead to the development of point-of-care assays to inform diagnosis, and to nominate new targets for drugs and vaccines to improve disease management and consequently to enhance the prognosis of children with bacterial meningitis.
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