{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:05:28Z","timestamp":1789643128181,"version":"4.0.0"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"40","license":[{"start":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T00:00:00Z","timestamp":1568592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"National Institute of Health","award":["U01-AI124319"],"award-info":[{"award-number":["U01-AI124319"]}]},{"name":"National Institute of Health","award":["R01-AI068804"],"award-info":[{"award-number":["R01-AI068804"]}]},{"name":"National Institute of Health","award":["K24-AI093969"],"award-info":[{"award-number":["K24-AI093969"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:p>\n                    The role of the host in development of persistent methicillin-resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (MRSA) bacteremia is not well understood. A cohort of prospectively enrolled patients with persistent methicillin-resistant\n                    <jats:italic>S. aureus<\/jats:italic>\n                    bacteremia (PB) and resolving methicillin-resistant\n                    <jats:italic>S. aureus<\/jats:italic>\n                    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 &gt; C polymorphism located in the\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    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 (\n                    <jats:italic>P<\/jats:italic>\n                    = 7.8 \u00d7 10\n                    <jats:sup>\u22126<\/jats:sup>\n                    ). Patients with MRSA bacteremia and g.25498283A &gt; C genotype exhibited significantly higher levels of methylation in gene-regulatory CpG island regions (\u0394methylation = 4.1%,\n                    <jats:italic>P<\/jats:italic>\n                    &lt; 0.0001) and significantly lower serum levels of interleukin-10 (IL-10) than patients with MRSA bacteremia without\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    mutation (A\/C: 9.7038 pg\/mL vs. A\/A: 52.9898 pg\/mL;\n                    <jats:italic>P<\/jats:italic>\n                    = 0.0042). Expression of\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    was significantly suppressed in patients with\n                    <jats:italic>S. aureus<\/jats:italic>\n                    bacteremia and in\n                    <jats:italic>S. aureus<\/jats:italic>\n                    -challenged primary human macrophages. Small interfering RNA (siRNA) silencing of\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    expression in human macrophages caused increased IL-10 response upon\n                    <jats:italic>S. aureus<\/jats:italic>\n                    stimulation. Treating macrophages with methylation inhibitor 5-Aza-2\u2032-deoxycytidine resulted in increased levels of IL-10 when challenged with\n                    <jats:italic>S. aureus<\/jats:italic>\n                    . In the murine sepsis model, methylation inhibition increased susceptibility to\n                    <jats:italic>S. aureus<\/jats:italic>\n                    . These findings indicate that g.25498283A &gt; C genotype within\n                    <jats:italic>DNMT3A<\/jats:italic>\n                    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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1909849116","type":"journal-article","created":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T20:35:58Z","timestamp":1568666158000},"page":"20087-20096","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":32,"title":["Genetic variation of DNA methyltransferase-3A contributes to protection against persistent MRSA bacteremia in patients"],"prefix":"10.1073","volume":"116","author":[{"given":"Felix","family":"Mba Medie","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Duke University 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