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

Abstract

Candida auris is an emerging fungal pathogen 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 in regards to its pathomechanisms still remain unelucidated. Since, microbial pathogenesis is modulated by a dynamic interplay between the host and the pathogen, dissecting such host-pathogen interaction involving C. auris can shed novel insights into its pathogenic cascade. As such, to further characterize the virulence repertoire of C. auris, this study applied an integrated quantitative proteomics strategy to scrutinize early-phase of infection. We utilized an in-vitro and an in-vivo experimental setup based on immune cells and murine model. Integrated proteomic analysis revealed a coordinated remodelling of cellular processes by C. auris during host-pathogen interaction, including downregulation of translational machinery, and modulation of molecules involved in metabolic rewiring, stress-response, and structural rearrangements. Collectively, these findings suggests that survival of C. auris under host-immune pressure is accompanied by rapid context-dependent molecular adaptations. Importance Candida auris is a critical high priority fungal pathogen classified by the World Health Organization (WHO) that constitute a serious threat to global health. Often termed as a ‘superbug’ due to its high transmissibility and multidrug resistant profile, the microbe has spread across the globe and is capable of causing high mortality rates. Molecular studies scrutinizing the pathogenic mechanisms of C. auris are limited and represents a major bottleneck to decipher and device intervention strategies against this enigmatic pathogen. As such, this study is aimed at widening the molecular knowledge spectrum of C. auris in regards to its virulence and pathogenesis. Here we dissect the host-pathogen interaction of C. auris by establishing experimental infection models and subsequently applying an integrated proteomics strategy to capture the organism’s virulence repertoire modulating fungal pathogenesis.