Candida albicans Virulence Traits in Commensalism and Disease

Abstract Purpose of Review Candida albicans is a common constituent of the normal human microbiota of the oro-gastrointestinal and vaginal tract. The immune system and the microbiota work together to maintain stable colonization and prevent excessive fungal growth and disease. Disruption of the delicate balance between C. albicans and the host can result in superficial and disseminated infections, as observed in individuals with a compromised immune system or dysbiosis. Invasive candidiasis accounts for a million deaths every year. C. albicans -intrinsic factors promoting stable commensalism in the human host are poorly established. Understanding the processes that regulate microbial homeostasis is important for evaluating novel intervention strategies that aim at targeting fungal virulence but at the same time prevent eradication of commensal organisms, which ultimately benefit the host. Recent Findings C. albicans commensalism is generally associated with a lack of filamentation, epithelial invasion and host cell damage. Fungal isolates recovered from healthy individuals are however not completely avirulent. In contrast, they exhibit varying degrees of virulence attributes and retain the capacity to cause disease, thereby challenging the notion that avirulence is a hallmark of superior commensal fitness. Recent advances in the field provide insights in how virulence traits, which are primarily known for inducing disease in the host, such as hyphae formation and candidalysin production, play an unexpected active part in establishing C. albicans gut commensalism. Overt filamentation and tissue damage is in turn prevented by adaptive antifungal immunity, which is induced in response to fungal virulence. Summary This review discusses the emerging paradigm shift in our understanding of how fungal virulence determinants are not per se inconsistent with commensalism but are actually a prerequisite for colonization and for triggering a host-protective homeostatic immunity through mutual adaptation with the host.