{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T15:04:35Z","timestamp":1792681475858,"version":"4.5.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T00:00:00Z","timestamp":1700784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIAID U01-AI124319"],"award-info":[{"award-number":["NIAID U01-AI124319"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIAID U19-AI172713-01"],"award-info":[{"award-number":["NIAID U19-AI172713-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R01-AI165671-01"],"award-info":[{"award-number":["1R01-AI165671-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Clinical outcomes in bacterial bloodstream infections (BSIs) are influenced by bacterial species, host immunity, and antibiotic therapy. The mechanisms by which such factors influence outcomes are poorly understood. We aimed to identify bacterial- and antibiotic-specific host transcriptional signatures in patients with bacterial BSI.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>RNA sequencing was performed on blood samples from patients with BSI due to gram-negative (GN) versus gram-positive (GP) pathogens: Escherichia coli (n = 30) or Klebsiella pneumoniae (n = 28) versus methicillin-susceptible Staphylococcus aureus (MSSA) (n = 24) or methicillin-resistant S. aureus (MRSA) (n = 58). Patients were matched by age, sex, and race.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>No significant host transcriptome differences were detected in patients with E. coli versus K. pneumoniae BSI, so these were considered together as GN BSI. Relative to S. aureus BSI, patients with GN BSI had increased activation of the classic complement system. However, the most significant signal was a reduction in host transcriptional signatures involving mitochondrial energy transduction and oxidative burst in MRSA versus MSSA. This attenuated host transcriptional signature remained after controlling for antibiotic therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Given the importance of immune cellular energetics and reactive oxygen species in eliminating hematogenous or intracellular MRSA, these findings may offer insights into its persistence relative to other bacterial BSIs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiad498","type":"journal-article","created":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T03:40:08Z","timestamp":1700883608000},"page":"1535-1545","source":"Crossref","is-referenced-by-count":7,"title":["Use of Transcriptional Signatures to Differentiate Pathogen-Specific and Treatment-Specific Host Responses in Patients With Bacterial Bloodstream Infections"],"prefix":"10.1093","volume":"229","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3250-0697","authenticated-orcid":false,"given":"Joshua T","family":"Thaden","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Duke University School of Medicine , Durham, North Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles , Los Angeles, California , USA"},{"name":"Institute for Quantitative and Computational Biosciences, University of California, Los Angeles , Los Angeles, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Ruffin","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Duke University School of Medicine , Durham, North Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W","family":"Gjertson","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of California, Los Angeles , Los Angeles, California , USA"},{"name":"Department of Pathology and Laboratory Medicine, University of California, Los Angeles , Los Angeles, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles , Los Angeles, California , USA"},{"name":"Institute for Quantitative and Computational Biosciences, University of California, Los Angeles , Los Angeles, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8048-0897","authenticated-orcid":false,"suffix":"Jr","given":"Vance G","family":"Fowler","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Duke University School of Medicine , Durham, North Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R","family":"Yeaman","sequence":"additional","affiliation":[{"name":"Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles , Los Angeles, California , USA"},{"name":"Department of Medicine, Divisions of Molecular Medicine and Infectious Diseases, Harbor-UCLA Medical Center , Torrance, California , USA"},{"name":"Institute for Infection & Immunity, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center , Torrance, California , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,11,24]]},"reference":[{"key":"2024051515183459600_jiad498-B1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.cmi.2019.10.031","article-title":"Burden of bacterial bloodstream infection\u2014a brief update on epidemiology and significance of multidrug-resistant pathogens","volume":"26","author":"Kern","year":"2020","journal-title":"Clin Microbiol Infect"},{"key":"2024051515183459600_jiad498-B2","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/AAC.01709-16","article-title":"Increased costs associated with bloodstream infections caused by multidrug-resistant gram-negative bacteria are due primarily to patients with hospital-acquired infections","volume":"61","author":"Thaden","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2024051515183459600_jiad498-B3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/AAC.02671-16","article-title":"Results from a 13-year prospective cohort study show increased mortality associated with bloodstream infections caused by Pseudomonas aeruginosa compared to other bacteria","volume":"61","author":"Thaden","year":"2017","journal-title":"Antimicrob Agents Chemother"},{"key":"2024051515183459600_jiad498-B4","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1093\/cid\/ciaa801","article-title":"Risk factors for recurrent Staphylococcus aureus bacteremia","volume":"72","author":"Choi","year":"2020","journal-title":"Clin Infect Dis"},{"key":"2024051515183459600_jiad498-B5","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/s13054-017-1696-z","article-title":"Timing of appropriate empirical antimicrobial administration and outcome of adults with community-onset bacteremia","volume":"21","author":"Lee","year":"2017","journal-title":"Crit Care"},{"key":"2024051515183459600_jiad498-B6","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1086\/313440","article-title":"Bacteremic pneumonia due to Staphylococcus aureus: a comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms","volume":"29","author":"Gonzalez","year":"1999","journal-title":"Clin Infect Dis"},{"key":"2024051515183459600_jiad498-B7","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2123017119","article-title":"Staphylococcus aureus induces a muted host response in human blood that blunts the recruitment of neutrophils","volume":"119","author":"Zwack","year":"2022","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024051515183459600_jiad498-B8","doi-asserted-by":"crossref","first-page":"6037","DOI":"10.1038\/s41598-021-84050-x","article-title":"Bacteria-host transcriptional response during endothelial invasion by Staphylococcus aureus","volume":"11","author":"Gronnemose","year":"2021","journal-title":"Sci Rep"},{"key":"2024051515183459600_jiad498-B9","doi-asserted-by":"crossref","first-page":"e0124877","DOI":"10.1371\/journal.pone.0124877","article-title":"RNA-Seq Analysis of the host response to Staphylococcus aureus skin and soft tissue infection in a mouse model","volume":"10","author":"Brady","year":"2015","journal-title":"PLoS One"},{"key":"2024051515183459600_jiad498-B10","doi-asserted-by":"crossref","first-page":"14268","DOI":"10.1038\/ncomms14268","article-title":"Host-inherent variability influences the transcriptional response of Staphylococcus aureus during in vivo infection","volume":"8","author":"Thanert","year":"2017","journal-title":"Nat Commun"},{"key":"2024051515183459600_jiad498-B11","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.chom.2017.10.020","article-title":"Antibiotic-induced changes to the host metabolic environment inhibit drug efficacy and alter immune function","volume":"22","author":"Yang","year":"2017","journal-title":"Cell Host Microbe"},{"key":"2024051515183459600_jiad498-B12","doi-asserted-by":"crossref","first-page":"4446","DOI":"10.1158\/0008-5472.CAN-15-1626","article-title":"Tetracycline antibiotics impair mitochondrial function and its experimental use confounds research","volume":"75","author":"Chatzispyrou","year":"2015","journal-title":"Cancer Res"},{"key":"2024051515183459600_jiad498-B13","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.molcel.2007.04.005","article-title":"The site of action of oxazolidinone antibiotics in living bacteria and in human mitochondria","volume":"26","author":"Leach","year":"2007","journal-title":"Mol Cell"},{"key":"2024051515183459600_jiad498-B14","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1002\/JLB.4HI0420-306R","article-title":"Frontline science: antibiotic treatment routes Mycobacterium avium to phagolysosomes without triggering proinflammatory cytokine production in human M\u03d5s","volume":"109","author":"Asberg","year":"2021","journal-title":"J Leukoc Biol"},{"key":"2024051515183459600_jiad498-B15","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1021\/acs.molpharmaceut.5b00035","article-title":"Phagocytosed clofazimine biocrystals can modulate innate immune signaling by inhibiting TNF\u03b1 and boosting IL-1RA secretion","volume":"12","author":"Yoon","year":"2015","journal-title":"Mol Pharm"},{"key":"2024051515183459600_jiad498-B16","doi-asserted-by":"crossref","first-page":"109750","DOI":"10.1016\/j.celrep.2021.109750","article-title":"Inappropriate use of antibiotics exacerbates inflammation through OMV-induced pyroptosis in MDR Klebsiella pneumoniae infection","volume":"36","author":"Ye","year":"2021","journal-title":"Cell Rep"},{"key":"2024051515183459600_jiad498-B17","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1038\/s41564-022-01237-2","article-title":"Integrated host-microbe plasma metagenomics for sepsis diagnosis in a prospective cohort of critically ill adults","volume":"7","author":"Kalantar","year":"2022","journal-title":"Nat Microbiol"},{"key":"2024051515183459600_jiad498-B18","doi-asserted-by":"crossref","first-page":"816631","DOI":"10.3389\/fmicb.2022.816631","article-title":"Metagenomic next-generation sequencing for the microbiological diagnosis of abdominal sepsis patients","volume":"13","author":"Li","year":"2022","journal-title":"Front Microbiol"},{"key":"2024051515183459600_jiad498-B19","doi-asserted-by":"crossref","first-page":"E12353","DOI":"10.1073\/pnas.1809700115","article-title":"Integrating host response and unbiased microbe detection for lower respiratory tract infection diagnosis in critically ill adults","volume":"115","author":"Langelier","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024051515183459600_jiad498-B20","doi-asserted-by":"crossref","first-page":"e1001916","DOI":"10.1371\/journal.pmed.1001916","article-title":"A molecular host response assay to discriminate between sepsis and infection-negative systemic inflammation in critically ill patients: discovery and validation in independent cohorts","volume":"12","author":"McHugh","year":"2015","journal-title":"PLoS Med"},{"key":"2024051515183459600_jiad498-B21","doi-asserted-by":"crossref","first-page":"e227299","DOI":"10.1001\/jamanetworkopen.2022.7299","article-title":"Prospective validation of a rapid host gene expression test to discriminate bacterial from viral respiratory infection","volume":"5","author":"Ko","year":"2022","journal-title":"JAMA Netw Open"},{"key":"2024051515183459600_jiad498-B22","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nrg2484","article-title":"RNA-Seq: a revolutionary tool for transcriptomics","volume":"10","author":"Wang","year":"2009","journal-title":"Nat Rev Genet"},{"key":"2024051515183459600_jiad498-B23","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1038\/nbt.3001","article-title":"The concordance between RNA-Seq and microarray data depends on chemical treatment and transcript abundance","volume":"32","author":"Wang","year":"2014","journal-title":"Nat Biotechnol"},{"key":"2024051515183459600_jiad498-B24","doi-asserted-by":"crossref","first-page":"eaax8978","DOI":"10.1126\/sciadv.aax8978","article-title":"Beyond mass spectrometry, the next step in proteomics","volume":"6","author":"Timp","year":"2020","journal-title":"Sci Adv"},{"key":"2024051515183459600_jiad498-B25","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1039\/C9RA08985C","article-title":"Mass spectrometry-based metabolomics in health and medical science: a systematic review","volume":"10","author":"Zhang","year":"2020","journal-title":"RSC Adv"},{"key":"2024051515183459600_jiad498-B26","author":"Andrews"},{"key":"2024051515183459600_jiad498-B27"},{"key":"2024051515183459600_jiad498-B28","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-Seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2024051515183459600_jiad498-B29","doi-asserted-by":"crossref","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"Gigascience"},{"key":"2024051515183459600_jiad498-B30","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Liao","year":"2014","journal-title":"Bioinformatics"},{"key":"2024051515183459600_jiad498-B31","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-Seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"2024051515183459600_jiad498-B32","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"2024051515183459600_jiad498-B33","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/j.molcel.2008.08.022","article-title":"Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation","volume":"32","author":"Pandey","year":"2008","journal-title":"Mol Cell"},{"key":"2024051515183459600_jiad498-B34","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.3390\/biom11111602","article-title":"KCNQ1OT1: an oncogenic long noncoding RNA","volume":"11","author":"Cagle","year":"2021","journal-title":"Biomolecules"},{"key":"2024051515183459600_jiad498-B35","doi-asserted-by":"crossref","first-page":"100165","DOI":"10.1016\/j.xjidi.2022.100165","article-title":"Peripheral blood gene expression profile of infants with atopic dermatitis","volume":"3","author":"Nousbeck","year":"2023","journal-title":"JID Innov"},{"key":"2024051515183459600_jiad498-B36","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1146\/annurev.iy.04.040186.002443","article-title":"The membrane attack complex of complement","volume":"4","author":"Muller-Eberhard","year":"1986","journal-title":"Annu Rev Immunol"},{"key":"2024051515183459600_jiad498-B37","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.chom.2018.10.005","article-title":"Mitochondria-derived vesicles deliver antimicrobial reactive oxygen species to control phagosome-localized Staphylococcus aureus","volume":"24","author":"Abuaita","year":"2018","journal-title":"Cell Host Microbe"},{"key":"2024051515183459600_jiad498-B38","doi-asserted-by":"crossref","first-page":"102225","DOI":"10.1016\/j.redox.2021.102225","article-title":"Mitochondria in human neutrophils mediate killing of Staphylococcus aureus","volume":"49","author":"Dunham-Snary","year":"2022","journal-title":"Redox Biol"},{"key":"2024051515183459600_jiad498-B39","doi-asserted-by":"crossref","first-page":"632","DOI":"10.4161\/hv.34414","article-title":"Efficacy profile of a bivalent Staphylococcus aureus glycoconjugated vaccine in adults on hemodialysis: phase III randomized study","volume":"11","author":"Fattom","year":"2015","journal-title":"Hum Vaccin Immunother"},{"key":"2024051515183459600_jiad498-B40","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1016\/j.vaccine.2003.11.034","article-title":"Development of StaphVAX, a polysaccharide conjugate vaccine against S. aureus infection: from the lab bench to phase III clinical trials","volume":"22","author":"Fattom","year":"2004","journal-title":"Vaccine"},{"key":"2024051515183459600_jiad498-B41","doi-asserted-by":"crossref","first-page":"1368","DOI":"10.1001\/jama.2013.3010","article-title":"Effect of an investigational vaccine for preventing Staphylococcus aureus infections after cardiothoracic surgery: a randomized trial","volume":"309","author":"Fowler","year":"2013","journal-title":"JAMA"},{"key":"2024051515183459600_jiad498-B42","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1093\/femsre\/fuz030","article-title":"Development of a vaccine against Staphylococcus aureus invasive infections: evidence based on human immunity, genetics and bacterial evasion mechanisms","volume":"44","author":"Miller","year":"2020","journal-title":"FEMS Microbiol Rev"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiad498\/53973943\/jiad498.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/229\/5\/1535\/57675598\/jiad498.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/229\/5\/1535\/57675598\/jiad498.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T15:19:16Z","timestamp":1715786356000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/229\/5\/1535\/7450149"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,24]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,11,24]]},"published-print":{"date-parts":[[2024,5,15]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiad498","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,5,15]]},"published":{"date-parts":[[2023,11,24]]}}}