Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Dual RNA-seq of clinical adult sepsis samples (TOPS study) to characterize host-pathogen interactions

ABSTRACT: Blood samples (0.5 ml) of 8 adults with blood culture-confirmed bacterial sepsis and 3 healthy adults were collected. A previously optimized host-bacterial RNA extraction protocol was used to isolate leukocyte and bacterial RNA. Purified RNA was depleted or rRNA and underwent deep sequencing using a 150 bp paired-end sequencing run on a NovaSeq 6000 (Illumina). Host and bacterial sequencing reads were aligned in silico and bioinformatic analyses were used to explore host and bacterial transcriptional responses during sepsis.

INSTRUMENT(S): NA, Illumina NovaSeq 6000

ORGANISM(S): Homo sapiens

SUBMITTER:

PROVIDER: E-MTAB-14713 | biostudies-arrayexpress |

SECONDARY ACCESSION(S): ERP167341

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Similar Datasets

Project description:Polymorphonuclear leukocytes (PMN) from patients with chronic granulomatous disease (CGD) fail to produce microbicidal concentrations of reactive oxygen species due to mutations in NOX2. Patients with CGD suffer from severe, life-threatening infections and inflammatory complications. Granulibacter bethesdensis is an emerging Gram-negative pathogen in CGD that resists killing by CGD PMN and inhibits PMN apoptosis through unknown mechanisms. Microarray analysis was used to study mRNA expression in normal and CGD PMN during incubation with G. bethesdensis and, simultaneously, in G. bethesdensis with normal and CGD PMN. We detected upregulation of anti-apoptotic genes (e.g., XIAP, GADD45B) and downregulation of pro-apoptotic genes (e.g., CASP8, APAF1) in infected PMN. Transcript and protein levels of inflammation and immunity-related genes were also altered. Upon interaction with PMN, G. bethesdensis altered expression of ROS-resistance genes in the presence of normal but not CGD PMN. Bacterial stress response genes, including ClpB, increased during phagocytosis by both normal and CGD PMN demonstrating responses to oxygen-independent PMN antimicrobial systems. Antisense knock down demonstrated that ClpB is dispensable for extracellular growth but is essential for bacterial resistance to both normal and CGD PMN. Metabolic adaptation of Granulibacter growth in PMN included upregulation of pyruvate dehydrogenase. Pharmacologic inhibition of pyruvate dehydrogenase by triphenylbismuthdichloride was lethal to Granulibacter. This study expands knowledge of microbial pathogenesis by Granulibacter in cells from permissive (CGD) and non-permissive (normal) hosts and identifies potentially druggable microbial factors, such as pyruvate dehydrogenase and ClpB, to help combat this antibiotic-resistant pathogen. pathogen time series 0-1-4-24 in CGD subjects and normals : host time series 0-1-4-24 in CGD subjects and normals non-infected and infected with Gb

Dataset Information

Dual RNA-seq of clinical adult sepsis samples (TOPS study) to characterize host-pathogen interactions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets