{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T18:59:38Z","timestamp":1772218778399,"version":"3.50.1"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005326","name":"Yale University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005326","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Infection in diabetic foot ulcers (DFUs) is one of the major complications associated with patients with diabetes. <jats:italic>Staphylococcus aureus<\/jats:italic> is the most common offending pathogen in patients with infected DFU. Previous studies have suggested the application of species-specific antibodies against <jats:italic>S. aureus<\/jats:italic> for diagnosis and monitoring treatment response. Early and accurate identification of the main pathogen is critical for management of DFU infection. Understanding the host immune response against species-specific infection may facilitate diagnosis and may suggest potential intervention options to promote healing infected DFUs. We sought to investigate evolving host transcriptome associated with surgical treatment of <jats:italic>S. aureus<\/jats:italic>\u2013 infected DFU.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study compared the transcriptome profile of 21 patients with <jats:italic>S. aureus<\/jats:italic>\u2013 infected DFU who underwent initial foot salvage therapy with irrigation and debridement followed by intravenous antibiotic therapy. Blood samples were collected at the recruitment (0 weeks) and 8 weeks after therapy to isolate peripheral blood mononuclear cells (PBMCs). We analyzed the PBMC expression of transcriptomes at two different time points (0 versus 8 weeks). Subjects were further divided into two groups at 8 weeks: healed (n = 17, 80.95%) versus non-healed (n = 4, 19.05%) based on the wound healing status. DESeq2 differential gene analysis was performed. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results and discussion<\/jats:title><jats:p>An increased expression of <jats:italic>IGHG1<\/jats:italic>, <jats:italic>IGHG2<\/jats:italic>, <jats:italic>IGHG3<\/jats:italic>, <jats:italic>IGLV3-21<\/jats:italic>, and <jats:italic>IGLV6-57<\/jats:italic> was noted during active infection at 0 weeks compared with that at 8 weeks. Lysine- and arginine-rich histones (<jats:italic>HIST1H2AJ<\/jats:italic>, <jats:italic>HIST1H2AL<\/jats:italic>, <jats:italic>HIST1H2BM<\/jats:italic>, <jats:italic>HIST1H3B<\/jats:italic>, and <jats:italic>HIST1H3G<\/jats:italic>) were upregulated at the initial phase of active infection at 0 weeks. <jats:italic>CD177<\/jats:italic> and <jats:italic>RRM2<\/jats:italic> were also upregulated at the initial phase of active infection (0 weeks) compared with that at 8 weeks of follow-up. Genes of heat shock protein members (<jats:italic>HSPA1A<\/jats:italic>, <jats:italic>HSPE1<\/jats:italic>, and <jats:italic>HSP90B1<\/jats:italic>) were high in not healed patients compared with that in healed patients 8 weeks after therapy. The outcome of our study suggests that the identification of genes evolution based on a transcriptomic profiling could be a useful tool for diagnosing infection and assessing severity and host immune response to therapies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2023.1198115","type":"journal-article","created":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T18:06:35Z","timestamp":1687802795000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Transcriptomic identification of genes expressed in invasive S. aureus diabetic foot ulcer infection"],"prefix":"10.3389","volume":"13","author":[{"given":"Taiwo Samuel","family":"Agidigbi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyuk-Kwon","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James R.","family":"Knight","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dejian","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francis Y.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irvin","family":"Oh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1056\/NEJMra1615439","article-title":"Diabetic foot ulcers and their recurrence","volume":"376","author":"Armstrong","year":"2017","journal-title":"N Engl. 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