Candida auris uses nutrient sensing to titrate its virulence potential and modulate immune response for host colonisation

Candida auris uses nutrient sensing to titrate its virulence potential and modulate immune response for host colonisation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Candida auris uses nutrient sensing to titrate its virulence potential and modulate immune response for host colonisation Ana Traven, Irma Tedja, Harshini Weerasinghe, Garrett Bryak, Aysha Sezmis, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8008141/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract The emergence of Candida auris as a pathogen required host adaptation and evasion of mammalian immunity, but the mechanisms are poorly understood. We discovered that C. auris uses nutrient sensing to tune its virulence potential and control immune activation in changing environments. In glucose-rich conditions (relevant to blood), C. auris suppresses its virulence traits and evades immune detection. Conversely, carbon sources prevalent in skin activate adhesion and filamentation, thereby triggering robust macrophage responses. In-depth phenotyping of multiple clinical strains revealed that C. auris generates phenotypic heterogeneity by titrating expression of key transcriptional regulators dependent on nutrient inputs and genetic background. This dials-up or -down its virulence potential and controls proportional immune responses and host colonisation. Therefore, metabolic flexibility enables C. auris to optimise a critical trade-off: expressing traits for tissue colonization while minimizing immune recognition. This establishes how C. auris adjusts its virulence and immune evasion to thrive in host environments. Biological sciences/Microbiology/Fungi/Fungal pathogenesis Biological sciences/Microbiology/Fungi/Fungal host response Full Text Additional Declarations There is NO Competing Interest. Supplementary Files TedjaetalFigureS8.pdf Supplementary Figure 8 TedjaetalDatasetS1Genomicanalyses.xlsx Dataset S1 TedjaetalDatasetS3Datausedinfigures.xlsx Dataset S3 TedjaetalDatasetS2RNAseqanalyses.xlsx Dataset S2 TedjaetalMovieS1.mp4 Movie S1 Cite Share Download PDF Status: Under Review Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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