The fascinating ability of Candida albicans to undergo dramatic changes in cellular morphology has invited speculation that this plasticity in form contributes to the virulence of the organism. Molecular genetic analyses have confirmed this hypothesis and further demonstrated that genes that govern cellular morphology are co-regulated with genes encoding conventional virulence factors such as proteases and adhesins. The transcriptional regulatory networks of C. albicans thus ensure that hyphae are produced concomitantly with virulence factors, resulting in cells that are adapted for invading the tissues of an immunocompromised host. Hyphae are able to exert mechanical force, aiding penetration of epithelial surfaces, and hyphae damage endothelial cells, aiding escape of C. albicans from the host bloodstream into deeper tissue. Hyphal morphogenesis is thus an integral part of the overall virulence strategy of C. albicans.

Candida albicans, an opportunistic fungal pathogen, causes a wide variety of human diseases such as oral thrush and disseminated candidiasis. Many aspects of C. albicans physiology have been studied during liquid growth, but in its natural environment, the gastrointestinal tract of a mammalian host, the organism associates with surfaces. Growth on a surface triggers several behaviors, such as biofilm formation, invasion, and thigmotropism, that are important for infection. Recent discoveries have identified factors that regulate these behaviors and revealed the importance of these behaviors for pathogenesis.

For mammalian cells, contact-dependent regulatory controls are crucially important for controlling cellular proliferation and preventing diseases such as cancer. Candida albicans , an opportunistic fungal pathogen that normally resides within a mammalian host, also exhibits contact-dependent cellular behaviors such as invasive hyphal growth and biofilm development. Results reported here demonstrate that, in C. albicans , physical contact results in activation of the mitogen-activated protein kinase Mkc1p. This kinase is part of the fungal cell integrity pathway, a signal transduction pathway known to be activated by cell wall stress. It is demonstrated here that Mkc1p is required for invasive hyphal growth and normal biofilm development. Therefore, Mkc1p signaling contributes to contact-dependent regulation. Because responding to contact appropriately allows coordinated cellular behavior in a metazoan, commensal C. albicans cells behave like a part of the host, using contact-activated signaling to regulate fungal behavior.

Interactions between colonizing commensal microorganisms and their hosts play important roles in health and disease. The opportunistic fungal pathogen Candida albicans is a common component of human intestinal flora. To gain insight into C. albicans colonization, genes expressed by fungi grown within a host were studied. The EFH1 gene, encoding a putative transcription factor, was highly expressed during growth of C. albicans in the intestinal tract. Counterintuitively, an efh1 null mutant exhibited increased colonization of the murine intestinal tract, a model of commensal colonization, whereas an EFH1 overexpressing strain exhibited reduced colonization of the intestinal tract and of the oral cavity of athymic mice, the latter situation modeling human mucosal candidiasis. When inoculated into the bloodstream of mice, both efh1 null and EFH1 overexpressing strains caused lethal infections. In contrast, other mutants are attenuated in virulence following intravenous inoculation but exhibited normal levels of intestinal colonization. Finally, although expression of several genes is dependent on transcription factor Efg1p during laboratory growth, Efg1p-independent expression of these genes was observed during growth within the murine intestinal tract. These results show that expression of EFH1 regulated the level of colonizing fungi, favoring commensalism as opposed to candidiasis. Also, different genes are required in different host niches and the pathway(s) that regulates gene expression during host colonization can differ from well-characterized pathways used during laboratory growth. Although the fungus Candida albicans commonly colonizes the human gastrointestinal tract as a commensal, the organism is also an opportunistic pathogen, responsible for a wide range of infections in immunocompromised persons. While numerous studies of infection have been conducted, few studies have analyzed the commensal state. The studies described here analyze C. albicans cells colonizing the intestinal tract of immunocompetent mice in the absence of disease, a model for commensalism. Results showed that expression of the putative transcription factor Efh1p by cells colonizing the intestinal tract was relatively high, but paradoxically, expression of Efh1p was associated with lower colonization. Efh1p had no detectable effect on the ability of C. albicans to cause lethal disseminated infection in mice. In contrast, Rbt1p and Rbt4p, two proteins of poorly defined function required for normal disseminated infection, were not required for intestinal colonization. These results argue that the commensal state is distinct from the pathogenic state and that different factors are important in different states. Also, the regulation of expression of genes RBT1, RBT4, and ECE1 during intestinal colonization differed from their well-characterized regulation during laboratory growth. Further studies of commensal colonization are needed to understand this important stage of C. albicans biology.