气候变化领域集成服务门户(CCPortal): Human DNA methylation signatures differentiate persistent from resolving MRSA bacteremia

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DOI	10.1073/pnas.2000663118
	Human DNA methylation signatures differentiate persistent from resolving MRSA bacteremia
	Chang Y.-L.; Rossetti M.; Gjertson D.W.; Rubbi L.; Thompson M.; Montoya D.J.; Morselli M.; Ruffin F.; Hoffmann A.; Pellegrini M.; Fowler V.G.; Jr.; Yeaman M.R.; Reed E.F.; MRSA Systems Immunology Group
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	DNA methylation; Epigenetics; MRSA; Persistence; Staphylococcus aureus
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180368
作者单位	Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, United States; Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, CA 90095, United States; Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, CA 90095, United States; School of Medicine, University of California, Davis, CA 95616, United States; Division of Infectious Diseases, Duke University, Durham, NC 27710, United States; Institute for Quantitative and Computational Biosciences, University of California, Los Angeles, CA 90095, United States; Division of Molecular Medicine, Harbor–University of California, Los Angeles Medical Center, Torrance, CA 90502, United States; Division of Infectious Diseases, Harbor–University of California, Los Angeles Medical Center, Torrance, CA 90502, United States; Lundquist Institute for Biomedical Innovation, Harbor–University of California,...
推荐引用方式 GB/T 7714	Chang Y.-L.,Rossetti M.,Gjertson D.W.,et al. Human DNA methylation signatures differentiate persistent from resolving MRSA bacteremia[J],2021,118(10).
APA	Chang Y.-L..,Rossetti M..,Gjertson D.W..,Rubbi L..,Thompson M..,...&MRSA Systems Immunology Group.(2021).Human DNA methylation signatures differentiate persistent from resolving MRSA bacteremia.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Chang Y.-L.,et al."Human DNA methylation signatures differentiate persistent from resolving MRSA bacteremia".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).