Proteome Remodelling in Candida auris During Early Host Adaptation In Vitro and In Vivo

Candida auris is an emerging fungal pathogen that is posing a serious global health threat due to its high transmissibility and multidrug resistance profile. Despite recent molecular advances in scrutinizing this enigmatic microbe, much of our understanding regarding its pathomechanisms remains unelucidated. Since microbial pathogenesis is modulated by a dynamic interplay between the host and the pathogen, dissecting such host-pathogen interactions involving C. auris can shed novel insights into its pathogenic cascade. As such, to characterize the virulence repertoire of C. auris, this study applied an integrated quantitative proteomics strategy to scrutinize the early phase of infection. In vitro and in vivo experimental setups based on macrophage co-culture and murine intraperitoneal infection were utilized. Integrated proteomic analysis revealed a coordinated remodelling of cellular processes by C. auris during the early host-pathogen interaction phase, including downregulation of translational machinery, modulation of molecules involved in metabolic rewiring, stress responses, and structural rearrangements. Several proteins associated with oxidative stress adaptation, alternative carbon metabolism, and cytoskeletal regulation were differentially abundant during host interactions. Collectively, these findings demonstrate that early adaptation of C. auris to host immune pressure involves rapid and context-dependent proteome remodelling that may contribute to fungal survival and persistence during infection.