{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:59:27Z","timestamp":1793642367201,"version":"4.5.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Extracellular vesicles (EVs) are important mediators of host\u2013microorganism communication at epithelial surfaces. However, their role in shaping corneal epithelial responses to ocular-associated bacteria remains poorly understood. Here, we investigated the species-specific effects of\n                      <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                      and\n                      <jats:italic>Staphylococcus epidermidis<\/jats:italic>\n                      on human corneal epithelial cells, focusing on bacterial extracellular vesicles (BEVs), direct microbial contact, and epithelial exosomal remodeling.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Human corneal epithelial cells were exposed to BEVs or co-cultured with\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      or\n                      <jats:italic>S. epidermidis<\/jats:italic>\n                      . Transcriptomic, proteomic, and extracellular vesicle RNA analyses were performed together with functional assays evaluating epithelial metabolic activity, motility, and apoptosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BEVs from\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      induced a strong pro-inflammatory epithelial response associated with IL-17, TNF, and NF-\u03baB signaling, extracellular matrix remodeling, and increased cell motility. Direct bacterial contact further amplified these effects, triggering extensive transcriptional reprogramming and remodeling of epithelial exosomal cargo, including enrichment of proteasome-associated proteins and apoptosis-related microRNAs. Functional apoptosis assays confirmed that exosomes released following\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      exposure acquired a modest but significant pro-apoptotic activity. In contrast,\n                      <jats:italic>S. epidermidis<\/jats:italic>\n                      induced a substantially milder transcriptional response characterized by limited differential gene expression, preferential detection of regulatory non-coding RNAs, and distinct exosomal remodeling associated with cell cycle and signaling pathways. Notably, responses induced by BEVs and direct bacterial contact showed limited overlap, indicating complementary mechanisms of epithelial regulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Together, these findings demonstrate that BEVs and direct microbial contact act as complementary and species-specific drivers of corneal epithelial reprogramming. Our results further support a model in which BEVs function as early signaling mediators, whereas epithelial-derived exosomes contribute to the propagation and modulation of these responses across the corneal epithelium.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1899147","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T05:55:21Z","timestamp":1786514121000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Bacterial extracellular vesicles and direct microbial contact drive species-specific corneal epithelial reprogramming"],"prefix":"10.3389","volume":"16","author":[{"given":"Noelia","family":"Blanco-Agud\u00edn","sequence":"first","affiliation":[{"name":"Instituto Universitario Fern\u00e1ndez-Vega (IUFV), Fundaci\u00f3n de Investigaci\u00f3n Oftalmol\u00f3gica","place":["Oviedo, Spain"]},{"name":"Departamento de Biolog\u00eda Funcional, University of Oviedo","place":["Oviedo, Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","place":["Oviedo, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suhui","family":"Ye","sequence":"additional","affiliation":[{"name":"Instituto Universitario Fern\u00e1ndez-Vega (IUFV), Fundaci\u00f3n de Investigaci\u00f3n Oftalmol\u00f3gica","place":["Oviedo, Spain"]},{"name":"Departamento de Biolog\u00eda Funcional, University of Oviedo","place":["Oviedo, Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","place":["Oviedo, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Gonz\u00e1lez-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Instituto Universitario Fern\u00e1ndez-Vega (IUFV), Fundaci\u00f3n de Investigaci\u00f3n Oftalmol\u00f3gica","place":["Oviedo, Spain"]},{"name":"Departamento de Biolog\u00eda Funcional, University of Oviedo","place":["Oviedo, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"Fern\u00e1ndez-Vega","sequence":"additional","affiliation":[{"name":"Instituto Universitario Fern\u00e1ndez-Vega (IUFV), Fundaci\u00f3n de Investigaci\u00f3n Oftalmol\u00f3gica","place":["Oviedo, Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","place":["Oviedo, Spain"]},{"name":"Department of Pathology, Hospital Universitario Central de Asturias (HUCA)","place":["Oviedo, Spain"]},{"name":"Biobank of Principality of Asturias","place":["Oviedo, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jes\u00fas","family":"Merayo-Lloves","sequence":"additional","affiliation":[{"name":"Instituto Universitario Fern\u00e1ndez-Vega (IUFV), Fundaci\u00f3n de Investigaci\u00f3n Oftalmol\u00f3gica","place":["Oviedo, Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","place":["Oviedo, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis M.","family":"Quir\u00f3s","sequence":"additional","affiliation":[{"name":"Instituto Universitario Fern\u00e1ndez-Vega (IUFV), Fundaci\u00f3n de Investigaci\u00f3n Oftalmol\u00f3gica","place":["Oviedo, Spain"]},{"name":"Departamento de Biolog\u00eda Funcional, University of Oviedo","place":["Oviedo, Spain"]},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA)","place":["Oviedo, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10123465","article-title":"Killing by degradation: regulation of apoptosis by the ubiquitin-proteasome system","volume":"10","author":"Abbas","year":"2021","journal-title":"Cells"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/vision5020027","article-title":"Ocular surface microbiota in contact lens users and contact-lens-associated bacterial keratitis","volume":"5","author":"Andersson","year":"2021","journal-title":"Vision"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00036-23","article-title":"Pseudomonas aeruginosa-derived extracellular vesicles modulate corneal inflammation: role in microbial keratitis","volume":"91","author":"Ayilam Ramachandran","year":"2023","journal-title":"Infect. 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