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The fungal organism Candida albicans is both a normal inhabitant of the human gastrointestinal tract and a potentially devastating nosocomial pathogen. Since infections by C. albicans arise from intestinal populations of organisms, successful establishment of intestinal colonization is a prerequisite for initiation of infection. Rosenbach et al. (p. 1075–1086) sought to understand how C. albicans colonizes the intestinal tract of a mammalian host. Transcriptome analysis showed that C. albicans cells colonizing a mammalian host had notable differences from more commonly studied laboratory-grown cells. For example, gene expression in colonizing cells both promoted the ability to grow rapidly (a characteristic of exponential-phase cells) and enhanced the ability to resist stresses (a characteristic of post-exponential-phase cells). In addition, sensing of environmental pH, oxygen levels, and carbon sources contributed to patterns of gene expression in colonizing cells. Similarities in gene expression in colonizing cells and cells invading host tissue during disease were found, showing that C. albicans cells adopt a particular cell surface when growing within a host in both situations. This increased understanding of colonization will contribute to our ability to detect, treat, and prevent C. albicans infection in susceptible individuals.