{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:59:55Z","timestamp":1780898395147,"version":"3.54.1"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Fungal Biol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetes mellitus significantly increases susceptibility to opportunistic fungal colonization; however, the genetic architecture underlying this vulnerability in Middle Eastern populations remains underexplored. Caspase recruitment domain-containing protein 9 (CARD9) is a fundamental adaptor in fungal sensing. While CARD9 deficiency is traditionally viewed as a rare pediatric immunodeficiency, we hypothesize that common CARD9 variants serve as significant predisposing factors for fungal burden in the adult diabetic population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A cohort of 107 diabetic participants (49.5% overweight\/obese) was screened for fungal colonization across multiple anatomical sites. Targeted sequencing of the\n                      <jats:italic>CARD9<\/jats:italic>\n                      gene was performed, using a bioinformatics pipeline for heterozygous peak calling (IUPAC ambiguity codes) and Ensembl VEP for variant annotation. Functional impacts were predicted using SIFT, PolyPhen-2, and PyMOL structural modeling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fungal colonization was prevalent, with\n                      <jats:italic>Aspergillus niger<\/jats:italic>\n                      complex (27.9%) being the most frequently identified organism. Genomic analysis identified the N-terminal CARD domain as a mutational \u201chotspot.\u201d We identified a high prevalence of homozygous damaging variants (52.7%), including p.Arg47His and p.Gly49Asp, which disrupt CARD domain stability. An additional 24.8% of the cohort displayed significant IUPAC-mixed heterozygous signals. Despite these genetic findings, a \u201cparadox of stability\u201d emerged: individuals with the highest microbial scores (4\u20135) often carried the reference sequence, while multivariate analysis identified obesity (OR: 1.85, p &amp;lt; 0.05) as the primary independent predictor of fungal burden.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings demonstrate that the diabetic population harbors a widespread, previously unrecognized deficiency in the Dectin-1\/CARD9 signaling pathway. This shifts the clinical narrative of\n                      <jats:italic>CARD9<\/jats:italic>\n                      from a \u201crare pediatric disease\u201d to a common genetic predisposition in adult patients with diabetes. While metabolic dysregulation may override genetic factors, the high frequency of CARD domain \u201chotspot\u201d mutations supports a precision medicine approach integrating\n                      <jats:italic>CARD9<\/jats:italic>\n                      genotyping with metabolic profiling to risk-stratify patients for early antifungal prophylaxis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/ffunb.2026.1825667","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:36:23Z","timestamp":1780896983000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Interplay between CARD9 genetic variants and fungal colonization patterns among patients with diabetes"],"prefix":"10.3389","volume":"7","author":[{"given":"Aiah M.","family":"Khateb","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Science, Taibah University","place":["Madina, Saudi Arabia"]},{"name":"Health and Life Research Center, Taibah University","place":["Medina, Saudi Arabia"]},{"name":"Special Infectious Agents Unit, King Fahd Medical Research Center, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahaf Ghazi","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Clinical Trial Management, King Abdullah International Medical Research Center (KAIMRC), King Saud Bin Abdulaziz University for Health Sciences, Ministry of National Guard - Health Affairs","place":["Jeddah, Saudi Arabia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lujain","family":"Alsweed","sequence":"additional","affiliation":[{"name":"Laboratory Department, Dr. Hamid S. 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