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

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 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, while whole-genome sequencing (WGS) of a global isolate collection demonstrated that the LBP phenotype has arisen independently multiple times.