Candida  (Fungus)

The opportunistic fungal pathogen Candida is the most common cause of invasive fungal disease in the world. Systemic candidiasis increases mortality and hospital length of stay, resulting in an estimated $1.7 billion in additional cost of care. In susceptible populations, the frequent and repeated use of a limited arsenal of antifungal drugs has led to the increasing incidence of antifungal-resistant candidiasis. Patients with multi-drug resistant Candida infections are less likely to survive. 

The Pathogen

Although there are hundreds of Candida species, only six cause major human disease: C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei and the emergent multidrug-resistant C. auris. In healthy adults, Candida  are normal microbiota of the gut, genitourinary tract and skin. Infection is held in check by robust host defenses and microbial antagonism between Candida and other commensals. If this balance between Candida, host response and bacterial microflora is disrupted via antibiotic treatment or immunosuppression, the fungus can cause localized or invasive disease. Virulence is mediated by factors including adhesins that allow Candida to bind host and artificial substrates, hydrolytic enzymes that degrade host immune components and tissues, and rapid adaptations to environmental changes (e.g. nutrient availability,  pH levels). These attributes allow Candida to colonize host surfaces, evade and survive immune responses, and persist in the patient. 



Thrush (superficial candidiasis) was first describe by Hippocrates in the 4th century B.C. as a symptom of severe underlying disease. However, it wasn’t until the early 1980s, when medical progress increased the use of immunosuppressive drugs, antibiotics, cytotoxic chemotherapies and transplantation, that invasive candidiasis was recognized as a major clinical threat to vulnerable patients. Despite antifungal treatment, bloodstream infection has an attributable mortality of 30-40% due to delay in diagnosis and initiation of appropriate treatment.  Examples of dangerous invasive forms of Candida include deep tissue abscesses in cancer patients, eye and central nervous infections in premature infants, and severe esophageal infections in AIDS patients.

Antifungal Resistance in Candida

Increasing antifungal resistance  has made Candida infections a problematic clinical challenge, especially with populations of susceptible patients on the rise. Some Candida species are intrinsically more resistant to fluconazole treatment, e.g. C. glabrata. Others acquire resistance rapidly, especially in patients with recurrent infection that must be repeatedly treated. Resistance mechanisms include efflux pumps (e.g. MDR1), enzyme mutations that prevent drug binding (e.g. the FKS1 mutation negating echinocandin function), overexpression antifungal target genes (e.g. ERG11) to overcome antifungal activity, and the evolution of compensatory survival pathways (e.g. Candida species that survive despite lower cell membrane ergosterol thereby reducing polyene susceptibility). The recent emergence of C. auris, overwhelmingly resistant to fluconazole, and occasionally resistant to echinocandins and AmpB, has led to outbreaks in hospital ICUs that are surprisingly difficult to contain.


Protein Controls Candida UTI

Candida UTI is prevalent in hospitalized patients who have received antibiotics or with indwelling catheters.  Tamm-Horsfall glycoprotein (THP) is the most abundant urine protein. CHARM investigators showed THP restricts urinary tract colonization by C. albicans. THP binds to C. albicans hyphae, but not the yeast form, in a manner dependent on fungal expression of the Als3 adhesion glycoprotein.

Read at Infection and Immunity