Host Adaptation at the Cost of Biofilm Formation Drives Outbreak Persistence of a Major Human Fungal Pathogen

However, the microbiological traits underlying the persistence of these outbreak strains remain poorly understood. Here, we show that DR-Cp isolates responsible for prolonged outbreaks across multiple countries exhibit a striking low-biofilm-producing (LBP) phenotype.

Unexpectedly, LBP strains (29T and 49B) display enhanced stress tolerance, cell wall masking, and immune evasion, leading to resistance against neutrophil and macrophage killing and increased survival in immune cell-rich organs during systemic infection. Genome-wide transcriptomic profiling revealed extensive metabolic and regulatory rewiring in LBP strains. Together, our findings challenge the prevailing view that robust biofilm formation underlies Candida outbreak persistence and instead reveal that host immune pressure selects for biofilm attenuation as an adaptive strategy promoting long-term persistence.