Human DNA methylation signatures differentiate persistent from resolving MRSA bacteremia
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA631270 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11741700.fastq.gz | Fastqsanger.gz | |||
| SRR11741701.fastq.gz | Fastqsanger.gz | |||
| SRR11741702.fastq.gz | Fastqsanger.gz | |||
| SRR11741703.fastq.gz | Fastqsanger.gz | |||
| SRR11741704.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 398 |
Similar Datasets
Project description:Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is life-threatening and occurs in up to 30% of MRSA bacteremia cases despite appropriate antimicrobial therapy. Isolates of MRSA that cause antibiotic-persistent MRSA bacteremia (APMB) typically have in vitro antibiotic susceptibilities equivalent to those causing antibiotic-resolving MRSA bacteremia (ARMB). Thus, persistence reflects host-pathogen interactions occurring uniquely in context of antibiotic therapy in vivo. However, host factors and mechanisms involved in APMB remain unclear. We compared DNA methylomes in circulating immune cells from patients experiencing APMB vs. ARMB. Overall, methylation signatures diverged in the distinct patient cohorts. Differentially methylated sites intensified proximate to transcription factor binding sites, primarily in enhancer regions. In APMB patients, significant hypo-methylation was observed in binding sites for CCAAT enhancer binding protein (C/EBP) and signal transducer / activator of transcription 1 (STAT1). In contrast, hypo-methylation in ARMB patients localized to glucocorticoid receptor and histone acetyltransferase p300 binding sites. These distinct methylation signatures were enriched in neutrophils and achieved a mean area under the curve of 0.85 when used to predict APMB using a classification model. These findings differentiate epigenotypes in patients experiencing APMB vs. ARMB, and suggest a risk stratification strategy for antibiotic persistence in patients treated for MRSA bacteremia.
2021-03-01 | GSE150144 | GEO
Project description:Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is life threatening and occurs in up to 30% of MRSA bacteremia cases despite appropriate antimicrobial therapy. Isolates of MRSA that cause antibiotic-persistent methicillin-resistant S. aureus bacteremia (APMB) typically have in vitro antibiotic susceptibilities equivalent to those causing antibiotic-resolving methicillin-resistant S. aureus bacteremia (ARMB). Thus, persistence reflects host-pathogen interactions occurring uniquely in context of antibiotic therapy in vivo. However, host factors and mechanisms involved in APMB remain unclear. We compared DNA methylomes in circulating immune cells from patients experiencing APMB vs. ARMB. Overall, methylation signatures diverged in the distinct patient cohorts. Differentially methylated sites intensified proximate to transcription factor binding sites, primarily in enhancer regions. In APMB patients, significant hypomethylation was observed in binding sites for CCAAT enhancer binding protein-β (C/EBPβ) and signal transducer/activator of transcription 1 (STAT1). In contrast, hypomethylation in ARMB patients localized to glucocorticoid receptor and histone acetyltransferase p300 binding sites. These distinct methylation signatures were enriched in neutrophils and achieved a mean area under the curve of 0.85 when used to predict APMB using a classification model. These findings validated by targeted bisulfite sequencing (TBS-seq) differentiate epigenotypes in patients experiencing APMB vs. ARMB and suggest a risk stratification strategy for antibiotic persistence in patients treated for MRSA bacteremia.
| S-EPMC7958259 | biostudies-literature
Project description:Persistent bacteremia caused by Staphylococcus aureus (SA), especially methicillin-resistant SA (MRSA), is a significant cause of morbidity and mortality. Despite susceptibility phenotypes in vitro, persistent MRSA strains fail to clear with appropriate anti-MRSA therapy during bacteremia in vivo. Thus, identifying the factors that cause such MRSA persistence is of direct and urgent clinical relevance. To address the dynamics of MRSA persistence in the face of host immunity and typical antibiotic regimens, we developed a mathematical model based on the overarching assumption that phenotypic heterogeneity is a hallmark of MRSA persistence. First, we applied an ensemble modeling approach and obtained parameter sets that satisfied the condition of a minimum inoculum dose to establish infection. Second, by simulating with the selected parameter sets under vancomycin therapy which follows clinical practices, we distinguished the models resulting in resolving or persistent bacteremia, based on the total SA exceeding a detection limit after five days of treatment. Third, to find key determinants that discriminate resolving and persistent bacteremia, we applied a machine learning approach and found that the immune clearance rate of persister cells is a key feature. But, fourth, when relapsing bacteremia was considered, the growth rate of persister cells was also found to be a key feature. Finally, we explored pharmacological strategies for persistent and relapsing bacteremia and found that a persister killer, but not a persister formation inhibitor, could provide for an effective cure the persistent bacteremia. Thus, to develop better clinical solutions for MRSA persistence and relapse, our modeling results indicate that we need to better understand the pathogen-host interactions of persister MRSAs in vivo.
| S-EPMC6622483 | biostudies-literature
Project description:Interventions: Analysis of bacteremia after ESD of the colon.
Primary outcome(s): Identification of bacteremia after ESD testing blood culture and 16SrRNA gene sequencing.
Study Design: Single arm Non-randomized
| 2623655 | ecrin-mdr-crc
Project description:DNA Methylation Signatures Differentiate Meningiomas from Normal Dura
| PRJNA737450 | ENA
Project description:The role of the host in development of persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is not well understood. A cohort of prospectively enrolled patients with persistent methicillin-resistant S. aureus bacteremia (PB) and resolving methicillin-resistant S. aureus bacteremia (RB) matched by sex, age, race, hemodialysis status, diabetes mellitus, and presence of implantable medical device was studied to gain insights into this question. One heterozygous g.25498283A > C polymorphism located in the DNMT3A intronic region of chromosome 2p with no impact in messenger RNA (mRNA) expression was more common in RB (21 of 34, 61.8%) than PB (3 of 34, 8.8%) patients (P = 7.8 × 10-6). Patients with MRSA bacteremia and g.25498283A > C genotype exhibited significantly higher levels of methylation in gene-regulatory CpG island regions (Δmethylation = 4.1%, P < 0.0001) and significantly lower serum levels of interleukin-10 (IL-10) than patients with MRSA bacteremia without DNMT3A mutation (A/C: 9.7038 pg/mL vs. A/A: 52.9898 pg/mL; P = 0.0042). Expression of DNMT3A was significantly suppressed in patients with S. aureus bacteremia and in S. aureus-challenged primary human macrophages. Small interfering RNA (siRNA) silencing of DNMT3A expression in human macrophages caused increased IL-10 response upon S. aureus stimulation. Treating macrophages with methylation inhibitor 5-Aza-2'-deoxycytidine resulted in increased levels of IL-10 when challenged with S. aureus In the murine sepsis model, methylation inhibition increased susceptibility to S. aureus These findings indicate that g.25498283A > C genotype within DNMT3A contributes to increased capacity to resolve MRSA bacteremia, potentially through a mechanism involving increased methylation of gene-regulatory regions and reduced levels of antiinflammatory cytokine IL-10.
| S-EPMC6778225 | biostudies-literature
Project description:DNA Methylation Signatures Differentiate Meningiomas from Normal Dura [OmniSNP]
| PRJNA737456 | ENA
Project description:DNA Methylation Signatures Differentiate Meningiomas from Normal Dura [HumanMethylation450]
| PRJNA737457 | ENA
Project description:We have performed a comprehensive transcriptional analysis of specific monocyte and macrophage (MM-CM-^X) subsets during an acute self-resolving inflammatory insult. Following initial induction of acute inflammation, tissue resident (Resident) MM-CM-^X are rapidly M-bM-^@M-^XclearedM-bM-^@M-^Y from the inflammatory foci, only becoming recoverable as inflammation resolves. Monocytes are recruited to the inflammatory lesion where they differentiate into MM-CM-^X. We term these monocyte-derived MM-CM-^X M-bM-^@M-^Xinflammation-associatedM-bM-^@M-^Y to distinguish them from Resident MM-CM-^X which are present throughout the inflammatory response and can renew during the resolution of inflammation by proliferation. Comparative analysis of the Mo and MM-CM-^X populations (both M-bM-^@M-^Xinflammation-associatedM-bM-^@M-^Y and Resident MM-CM-^X) identifies select genes expressed in subsets of M-bM-^@M-^Xinflammation-associatedM-bM-^@M-^Y and Resident MM-CM-^X that play important roles in the resolution of inflammation and/or for immunity, including molecules involved in antigen presentation, cell cycle and others associated with M-bM-^@M-^XimmaturityM-bM-^@M-^Y and MM-CM-^X activation. We purified monocyte and macrophage populations from the peritoneal cavity of C57BL/6 mice 4, 18, 72 and 168 hours after the induction of inflammation with intraperitoneal administration of zymosan (2x10^7 particles). We also purified tissue resident macrophages and Ly-6B+ bone marrow monocytes from naive mice as reference populations.
2014-05-09 | E-GEOD-28621 | biostudies-arrayexpress
Project description:We have performed a comprehensive transcriptional analysis of specific monocyte and macrophage (MØ) subsets during an acute self-resolving inflammatory insult. Following initial induction of acute inflammation, tissue resident (Resident) MØ are rapidly ‘cleared’ from the inflammatory foci, only becoming recoverable as inflammation resolves. Monocytes are recruited to the inflammatory lesion where they differentiate into MØ. We term these monocyte-derived MØ ‘inflammation-associated’ to distinguish them from Resident MØ which are present throughout the inflammatory response and can renew during the resolution of inflammation by proliferation. Comparative analysis of the Mo and MØ populations (both ‘inflammation-associated’ and Resident MØ) identifies select genes expressed in subsets of ‘inflammation-associated’ and Resident MØ that play important roles in the resolution of inflammation and/or for immunity, including molecules involved in antigen presentation, cell cycle and others associated with ‘immaturity’ and MØ activation.
2014-05-09 | GSE28621 | GEO