{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:01:25Z","timestamp":1773014485204,"version":"3.50.1"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T00:00:00Z","timestamp":1742947200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea (NRF)","doi-asserted-by":"publisher","award":["2021R1F1A1046464"],"award-info":[{"award-number":["2021R1F1A1046464"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Microbial contamination of platelet concentrates (PC) remains a persistent challenge in transfusion medicine, necessitating robust preventive measures prior to product release. Differentially expressed gene (DEG) analysis of microbe inoculated PC offers a promising approach to identifying potential biomarkers for contamination detection. Within PC, each S. aureus (ATCC 29213) and S. epidermidis (ATCC 12228) was inoculated in a 103 CFU\/mL concentration. Total RNA was extracted from the samples at predetermined time points (0-, 1-, 3-, and 6-hours post-inoculation), followed by high-throughput RNA sequencing. DEG, gene enrichment, and pathway analysis were conducted. Diagnostic potential was evaluated through the calculation of area under the curve (AUC) values and the assessment of additional performance metrics. DEG identified 5884 and 974 DEGs in S. aureus and S. epidermidis samples, respectively. Pathway analysis revealed distinct biological responses: S. aureus-inoculated samples showed prominent enrichment in ribosomal and spliceosome pathways, while S. epidermidis-inoculated samples demonstrated significant activation of mitogen-activated protein kinase (MAPK) signaling pathways and natural killer (NK) cell-mediated cytotoxicity pathways. ROC analysis of the commonly differentially expressed genes in both S. aureus and S. epidermidis-inoculated samples demonstrated significant diagnostic potential. The genes H19, CAVIN1, A2M, and EPAS1 exhibited statistically significant adjusted p-values and AUC values exceeding 0.8, with the exception of the H19 gene in S. epidermidis, suggesting their utility as potential biomarkers for staphylococcal contamination detection. Interaction between PC and microbial contaminants resulted in DEG and genes could be analyzed for microbial contamination of PC. However, to establish the robustness and broader applicability of these findings, further studies encompassing a more diverse range of microbial species are necessary.<\/jats:p>","DOI":"10.3390\/ijms26073009","type":"journal-article","created":{"date-parts":[[2025,3,26]],"date-time":"2025-03-26T04:17:14Z","timestamp":1742962634000},"page":"3009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alterations in RNA Expression Profile Following S. aureus and S. epidermidis Inoculation into Platelet Concentrates"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0928-9109","authenticated-orcid":false,"given":"Jae Kwon","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taewon","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea"},{"name":"Research and Development Institute for In Vitro Diagnostic Medical Devices, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Youngeun","family":"Kweon","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1505-846X","authenticated-orcid":false,"given":"In Young","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5870-915X","authenticated-orcid":false,"given":"Eun-Jee","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea"},{"name":"Research and Development Institute for In Vitro Diagnostic Medical Devices, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeon-Joon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea"},{"name":"Research and Development Institute for In Vitro Diagnostic Medical Devices, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonggoo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8980-8177","authenticated-orcid":false,"given":"Hoon Seok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong Wook","family":"Jekarl","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Republic of Korea"},{"name":"Research and Development Institute for In Vitro Diagnostic Medical Devices, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Scridon, A. (2022). Platelets and Their Role in Hemostasis and Thrombosis-From Physiology to Pathophysiology and Therapeutic Implications. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232112772"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1182\/hematology.2020000135","article-title":"Does ABO and RhD matching matter for platelet transfusion?","volume":"2020","author":"Dunbar","year":"2020","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_3","first-page":"321","article-title":"The effect of platelet storage temperature on haemostatic, immune, and endothelial function: Potential for personalised medicine","volume":"17","author":"Shea","year":"2019","journal-title":"Blood Transfus."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1080\/09537104.2021.1961711","article-title":"Current challenges in platelet transfusion","volume":"33","author":"Smethurst","year":"2022","journal-title":"Platelets"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1186\/s13054-018-2212-9","article-title":"Bacterial contamination of platelets for transfusion: Strategies for prevention","volume":"22","author":"Levy","year":"2018","journal-title":"Crit. Care"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1159\/000499349","article-title":"Microbiological Screening of Platelet Concentrates in Europe","volume":"46","author":"Prax","year":"2019","journal-title":"Transfus. Med. Hemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1111\/trf.17136","article-title":"Assessment of polymicrobial interactions in bacterial isolates from transfused platelet units associated with sepsis","volume":"62","author":"Kerantzas","year":"2022","journal-title":"Transfusion"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1960","DOI":"10.1111\/trf.15951","article-title":"Sepsis from an apheresis platelet contaminated with Acinetobacter calcoaceticus\/baumannii complex bacteria and Staphylococcus saprophyticus after pathogen reduction","volume":"60","author":"Fridey","year":"2020","journal-title":"Transfusion"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1111\/vox.13272","article-title":"Isbt Transfusion-Transmitted Infectious Diseases Working Party SoB. Residual risks of bacterial contamination for pathogen-reduced platelet components","volume":"117","author":"Cloutier","year":"2022","journal-title":"Vox Sang."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/tme.12458","article-title":"Bacterial contamination of platelet components not detected by BacT\/ALERT\u00ae","volume":"28","author":"Abela","year":"2018","journal-title":"Transfus. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1111\/trf.15762","article-title":"Bacterial contamination rate of platelet components by primary culture: A systematic review and meta-analysis","volume":"60","author":"White","year":"2020","journal-title":"Transfusion"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1111\/trf.14085","article-title":"Bacterial screening of platelet components by National Health Service Blood and Transplant, an effective risk reduction measure","volume":"57","author":"McDonald","year":"2017","journal-title":"Transfusion"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Jacobs, M.R., Zhou, B., Tayal, A., and Maitta, R.W. (2024). Bacterial Contamination of Platelet Products. Microorganisms, 12.","DOI":"10.3390\/microorganisms12020258"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1586\/14737159.6.6.865","article-title":"Applications of real-time PCR in the screening of platelet concentrates for bacterial contamination","volume":"6","author":"Mohammadi","year":"2006","journal-title":"Expert. Rev. Mol. Diagn."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1111\/tme.12704","article-title":"Skin flora and bacterial contamination of diversion pouch and recovered platelet components in Moroccan blood donors","volume":"30","author":"Benajiba","year":"2020","journal-title":"Transfus. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1182\/hematology.2022000402","article-title":"Platelet components and bacterial contamination: Hospital perspective 2022","volume":"2022","author":"Szczepiorkowski","year":"2022","journal-title":"Hematol. Am. Soc. Hematol. Educ. Program"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1111\/trf.16776","article-title":"Acquired platelet storage container leaks and contamination with environmental bacteria: A preventable cause of bacterial sepsis","volume":"62","author":"Gammon","year":"2022","journal-title":"Transfusion"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1111\/vox.13283","article-title":"Isbt Transfusion-Transmitted Infectious Diseases Working Party SoB. Current status of rapid bacterial detection methods for platelet components: A 20-year review by the ISBT Transfusion-Transmitted Infectious Diseases Working Party Subgroup on Bacteria","volume":"117","author":"Schmidt","year":"2022","journal-title":"Vox Sang."},{"key":"ref_19","unstructured":"AABB (2024, May 24). Clinical Recognition and Investigation of Suspected Bacterial Contamination of Platelets. Available online: http:\/\/www.aabb.org\/programs\/publications\/bulletins\/Documents\/ab14-04.pdf."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/s41576-019-0150-2","article-title":"RNA sequencing: The teenage years","volume":"20","author":"Stark","year":"2019","journal-title":"Nat. Rev. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1101\/pdb.top084970","article-title":"RNA Sequencing and Analysis","volume":"2015","author":"Kukurba","year":"2015","journal-title":"Cold Spring Harb. Protoc."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Deshpande, D., Chhugani, K., Chang, Y., Karlsberg, A., Loeffler, C., Zhang, J., Muszy\u0144ska, A., Munteanu, V., Yang, H., and Rotman, J. (2023). RNA-seq data science: From raw data to effective interpretation. Front. Genet., 14.","DOI":"10.3389\/fgene.2023.997383"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1038\/s41596-019-0139-5","article-title":"RNA sequencing and swarm intelligence-enhanced classification algorithm development for blood-based disease diagnostics using spliced blood platelet RNA","volume":"14","author":"Best","year":"2019","journal-title":"Nat. Protoc."},{"key":"ref_24","first-page":"146","article-title":"Whole transcriptome analysis of platelet concentrates during storage","volume":"21","author":"Heililahong","year":"2023","journal-title":"Blood Transfus."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Supernat, A., Popeda, M., Pastuszak, K., Best, M.G., Gre\u0161ner, P., Veld, S.I.T., Siek, B., Bednarz-Knoll, N., Rondina, M.T., and Stokowy, T. (2021). Transcriptomic landscape of blood platelets in healthy donors. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-94003-z"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Nuhrenberg, T.G., Stockle, J., Marini, F., Zurek, M., Gr\u00fcning, B.A., Benes, V., Hein, L., Neumann, F.J., Stratz, C., and Cederqvist, M. (2022). Impact of high platelet turnover on the platelet transcriptome: Results from platelet RNA-sequencing in patients with sepsis. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0260222"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1182\/blood.2019000067","article-title":"Sepsis alters the transcriptional and translational landscape of human and murine platelets","volume":"134","author":"Middleton","year":"2019","journal-title":"Blood"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Schroeder, A., Mueller, O., Stocker, S., Salowsky, R., Leiber, M., Gassmann, M., Lightfoot, S., Menzel, W., Granzow, M., and Ragg, T. (2006). The RIN: An RNA integrity number for assigning integrity values to RNA measurements. BMC Mol. Biol., 7.","DOI":"10.1186\/1471-2199-7-3"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kim, J.T., Kim, Y., Kim, J.Y., Lee, S., Kim, M., and Jekarl, D.W. (2023). Regulatory Mechanism between Ferritin and Mitochondrial Reactive Oxygen Species in Spinal Ligament-Derived Cells from Ossification of Posterior Longitudinal Ligament Patient. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032872"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wang, B., Suen, C.W., Ma, H., Wang, Y., Kong, L., Qin, D., Lee, Y.W.W., and Li, G. (2020). The Roles of H19 in Regulating Inflammation and Aging. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.579687"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Vandooren, J., and Itoh, Y. (2021). Alpha-2-Macroglobulin in Inflammation, Immunity and Infections. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.803244"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.diagmicrobio.2016.01.003","article-title":"Centers for Disease Control and Prevention (CDC) Prevention Epicenters Program. Combined biomarkers discriminate a low likelihood of bacterial infection among surgical intensive care unit patients with suspected sepsis","volume":"85","author":"Kelly","year":"2016","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Schweizer, R.M., Velotta, J.P., Ivy, C.M., Jones, M.R., Muir, S.M., Bradburd, G.S., Storz, J.F., Scott, G.R., and Cheviron, Z.A. (2019). Physiological and genomic evidence that selection on the transcription factor Epas1 has altered cardiovascular function in high-altitude deer mice. PLoS Genet., 15.","DOI":"10.1371\/journal.pgen.1008420"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1038\/s41586-021-04131-9","article-title":"Accuracy mechanism of eukaryotic ribosome translocation","volume":"600","author":"Djumagulov","year":"2021","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1038\/s41392-022-01285-4","article-title":"Ribosome biogenesis in disease: New players and therapeutic targets","volume":"8","author":"Jiao","year":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2512","DOI":"10.18632\/aging.101922","article-title":"Impaired ribosome biogenesis: Mechanisms and relevance to cancer and aging","volume":"11","author":"Turi","year":"2019","journal-title":"Aging"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.bbapap.2005.08.017","article-title":"MAPK signalling pathways as molecular targets for anti-inflammatory therapy\u2014from molecular mechanisms to therapeutic benefits","volume":"1754","author":"Kaminska","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41568-022-00491-0","article-title":"Natural killer cells in antitumour adoptive cell immunotherapy","volume":"22","author":"Laskowski","year":"2022","journal-title":"Nat. Rev. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Elemam, N.M., Ramakrishnan, R.K., Hundt, J.E., Halwani, R., Maghazachi, A.A., and Hamid, Q. (2021). Innate Lymphoid Cells and Natural Killer Cells in Bacterial Infections: Function, Dysregulation, and Therapeutic Targets. Front. Cell Infect. Microbiol., 11.","DOI":"10.3389\/fcimb.2021.733564"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1080\/17474086.2016.1254546","article-title":"Role of natural killer cells in antibacterial immunity","volume":"9","author":"Schmidt","year":"2016","journal-title":"Expert. Rev. Hematol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.4049\/jimmunol.136.3.1081","article-title":"Natural cytotoxic effector cell activity against Shigella flexneri-infected HeLa cells","volume":"136","author":"Klimpel","year":"1986","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Kim, K.S., Kang, T., and Jekarl, D.W. (2024). Immune Gene Networks from Lung Cancer Patients Treated with Immune Checkpoint Inhibitors. Biomedicines, 12.","DOI":"10.3390\/biomedicines12030628"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ulgen, E., Ozisik, O., and Sezerman, O.U. (2019). pathfindR: An R Package for Comprehensive Identification of Enriched Pathways in Omics Data Through Active Subnetworks. Front. Genet., 10.","DOI":"10.3389\/fgene.2019.00858"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/3009\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:00:19Z","timestamp":1760029219000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/7\/3009"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,26]]},"references-count":44,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26073009"],"URL":"https:\/\/doi.org\/10.3390\/ijms26073009","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,26]]}}}