Infections caused by pathogenic yeasts, including Candida species, are becoming increasingly prevalent, infecting billions of people every year. Candida species rank as the fourth most common microbial agent causing bloodstream infections, with C. albicans and C. glabrata being the two most prominent species, followed by C. parapsilosis complex and C. tropicalis. Together, these four species are responsible for 90% of all Candida diseases and infections are generally nosocomial and associated with the use of intravascular catheters, abdominal surgery and corticosteroid therapy. A median value of 5.9 per 100,000 inhabitants allows an estimate5 of the annual global incidence of Candida infections at 400,000 cases, with most occurring in economically developed regions. Crude and attributable mortality rates of 42% and 27%, respectively, are high. The exact epidemiology of Invasive Fungal Diseases (IFDs) is unknown, since they are extremely difficult to diagnose. Major patient affected groups are leukaemia, transplant, and critical care patients. IFDs remain understudied and underdiagnosed as compared to other infectious diseases as those caused by bacteria. Currently there is no sensitive, rapid and accurate diagnostic assay for IFDs, nor is there an efficient way to monitor the success of antifungal therapy.

Current in vitro diagnostic (IVD) approaches have major limitations; direct observation of yeasts and the detection of diagnostic antigens, such as mannan, lack sensitivity and specificity. Without reliable IFD tests, treatment is delayed and non-targeted, and the outcome is devastating. Rates of acute respiratory failure, prolonged mechanical ventilation and days on intensive care unit (ICU) are increased by IFD10. Delayed treatment increases mortality of candidaemia by 10% per day.

Cost is largely driven by the current empirical treatment approach given the difficulty of determining the infective agent. Due to the frequent need to treat suspected cases, fungal infections are the most expensive opportunistic infections in immunosuppressed patients with annual costs of ~200€ million in Europe. In-hospital stays are complicated by additional costs underlining the socio-economic relevance of IFD. In fact, in a common clinical scenario, patients with fever and high risk for sepsis receive antibiotics to treat an assumed bacterial infection. This treatment, however, removes the protective gut microbiota and may trigger ​overgrowth by Candida, followed by translocation into the bloodstream and spread to organs. In addition, prolonged treatment is costly and leads to drug resistance. Importantly, some Candida species are inherently more resistant to certain antifungals, such as C. glabrata and C. krusei to fluconazole, or C. parapsilosis and C. glabrata to echinocandins. This growing resistance has serious implications for the management of infections, as a limited number of drugs are available. Finally, the specific and temporal infection-associated interactions between the human host and the yeast, and expression of disease-related biomarkers remain largely uncharacterized, which makes it difficult to distinguish the different stages of a threatening infection from those of harmless colonization. Candida infections are predominantly endogenous, which implies a transition from harmless commensal growth to either superficial infections or invasive infection. This may result from (a) direct invasion into epithelial tissues, (b) damage of barriers caused by surgery, polytrauma or drug treatment, or (c) spread from biofilms on medical devices. The transition from colonization to invasive growth is a dynamic process with distinct stages, each of which is characterized by the expression of specific factors. Therefore, it should be possible to discriminate, on a molecular level, between colonizing, superficial infecting and invasive cells.