{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:37:40Z","timestamp":1792197460957,"version":"4.4.0"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"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. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p><jats:italic>Cryptococcus neoformans (Cn)<\/jats:italic> is an encapsulated, neurotrophic\u00a0fungus that can cause life-threatening meningoencephalitis in immunocompromised individuals. Phospholipase B1 (PLB1) promotes <jats:italic>Cn<\/jats:italic> adhesion and colonization, however its role in fungal biofilm formation is not entirely clear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated how PLB1 is involved in <jats:italic>Cn<\/jats:italic> infection using a stereotaxic intracerebral infection mouse model, microscopy, whole-genome sequencing, and biophysical methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results showed that the <jats:italic>PLB1-<\/jats:italic>disrupted strain exhibited reduced survival and capsular polysaccharide (CPS) dissemination throughout brain tissue and elicited a stronger microglial response <jats:italic>in vivo<\/jats:italic>. Moreover, <jats:italic>Cn<\/jats:italic> adhesion to SH-SY5Y human neuroblastoma cells was weakened in the <jats:italic>PLB1-<\/jats:italic>disrupted strain, and <jats:italic>in vitro<\/jats:italic> biofilm formation showed reduced metabolic activity and thickness. Both the <jats:italic>PLB1-<\/jats:italic>disrupted and -reconstituted strains showed structural alterations; nevertheless, CPS production was increased in the <jats:italic>PLB1<\/jats:italic>-disrupted cells. We show that PLB1 is essential for maintaining capsular elasticity, regulating CPS secretion, and biofilm formation, which are critical for fungal colonization and cryptococcoma formation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results emphasize the need for further investigation into the mechanisms underlying the pathogenicity of <jats:italic>Cn<\/jats:italic>. In addition, our findings provide further evidence to validate PLB1 as an important antifungal target.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1681033","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T05:42:14Z","timestamp":1760506934000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Cryptococcus neoformans phospholipase B1 is critical for cryptococcoma formation in the mouse brain"],"prefix":"10.3389","volume":"16","author":[{"given":"Melissa E.","family":"Munzen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glauber R.","family":"de Sousa Ara\u00fajo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed 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