<i>Ocimum gratissimum</i> (Linnaeus) essential oil disrupts <i>Candida albicans</i> biofilms via morphogenetic suppression and stress reprogramming: translational implications for antifungal prophylaxis

<i>Ocimum gratissimum</i> L. (African basil) is widely used in ethnomedicine to treat infectious and inflammatory conditions, yet its antifungal mechanisms remain unclear. In this study, we evaluated the essential oil of <i>O. gratissimum</i> L. (OGEO) against <i>Candida albicans</i> biofilms, a clinically relevant driver of antifungal resistance in device-associated infections. Gas chromatography-mass spectrometry identified eugenol as the predominant constituent (59.5%), supported by terpenoid and sesquiterpene derivatives. Functional assays demonstrated potent antibiofilm activity, as exposure to 1% and 2% OGEO reduced viable biofilm cells by >2 log₁₀ CFU/biofilm at Day 1 and sustained ∼70% inhibition at Day 3, with corresponding biomass reductions of ∼65% and ∼80%, respectively. Confocal microscopy revealed marked thinning and fragmentation of hyphal networks, while scanning electron microscopy confirmed collapse of extracellular matrix architecture. Kinetic modeling showed that OGEO induced an intermediate suppression profile, delaying biofilm recovery compared to untreated controls and fluconazole (which permitted ∼90% regrowth by Day 7), but without the sustained fungicidal effect observed with caspofungin (>80% suppression). Transcriptomic profiling at Day 3 identified 463 differentially expressed genes, with strong repression of hyphal regulators (<i>HWP1, ALS3, EFG1, BCR1</i>) and extracellular matrix-associated genes (<i>FKS1, ZAP1</i>), alongside upregulation of oxidative and proteotoxic stress pathways (<i>SOD5</i>, <i>HSP90</i>, MAPK signaling). Together, these data suggest that OGEO functions as a biofilm modulator rather than a fungicidal agent, weakening structural resilience and redirecting <i>C. albicans</i> into a stress-adaptive state. Clinically, this modulatory activity-marked by early biomass suppression, matrix destabilization, and transcriptional remodeling-highlights OGEO's potential as a prophylactic or adjunctive strategy in device-associated candidiasis. Applications may include medical device coatings or topical formulations that prevent biofilm initiation and enhance susceptibility to existing antifungal drugs.