biostudies-literatureUnknown14(1)Yang DCandida albicans is a benign member of gut microbiota, but also causes life-threatening disseminated infections, suggesting that this fungus commensalism has evolved with retention of virulence traits. Here we reveal that N-acetylglucosamine (GlcNAc) enables C. albicans to balance between commensalism and pathogenesis. Although GlcNAc catabolism is beneficial for commensal growth of C. albicans, deleting GlcNAc sensor-transducer Ngs1 confers enhanced fitness, indicating that GlcNAc signaling is detrimental to commensalism. Interestingly, addition of GlcNAc attenuates commensal fitness of gut-evolved C. albicans but retains its disease-causing potential. We further demonstrate that GlcNAc is a major inducer of hypha-associated transcription in the gut, which represents the key determinant fNature communications3796https://www.ebi.ac.uk/biostudies/studies/S-EPMC10293180biostudies-literatureCandida albicans exploits N-acetylglucosamine as a gut signal to establish the balance between commensalism and pathogenesis.PMC10293180Su CLu YZhang MYang DDong BfalseCandida albicans exploits N-acetylglucosamine as a gut signal to establish the balance between commensalism and pathogenesis.Candida albicans is a benign member of gut microbiota, but also causes life-threatening disseminated infections, suggesting that this fungus commensalism has evolved with retention of virulence traits. Here we reveal that N-acetylglucosamine (GlcNAc) enables C. albicans to balance between commensalism and pathogenesis. Although GlcNAc catabolism is beneficial for commensal growth of C. albicans, deleting GlcNAc sensor-transducer Ngs1 confers enhanced fitness, indicating that GlcNAc signaling is detrimental to commensalism. Interestingly, addition of GlcNAc attenuates commensal fitness of gut-evolved C. albicans but retains its disease-causing potential. We further demonstrate that GlcNAc is a major inducer of hypha-associated transcription in the gut, which represents the key determinant f2023-01-01T00:00:00Z2023 Jun2025-04-04T22:17:46.581Z2025-04-04T22:17:46.581ZS-EPMC102931803736516010.1038/s41467-023-39284-w