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Salem Health: Infectious Diseases & Conditions, 2nd Edition

Candida

by Richard W. Cheney Jr.

Category: Pathogen

Transmission route: Direct contact

Definition

Candida is a genus of often polymorphic yeasts that consists of more than 350 species. Some species of Candida live on and inside the human body. These organisms can cause disease in healthy individuals but can cause severe infections in persons with compromised immune systems.

Causes

Many species of Candida have been isolated from humans and other animals (e.g., birds, arthropods, fish, etc.), animal wastes, mushrooms, plants, soil, freshwater, seawater, fermentation and dairy products, high-sugar substrates (e.g., honey, grapes, nectar), and airborne particles. They are so common that most humans support commensal (i.e. associated with another organism without harming it) Candida spp. on their skin and exposed mucous membranes, and virtually all human gastrointestinal tracts host at least one species of Candida. C. guilliermondii and C. parapsilosis are common microbial residents on human skin, and C. albicans, C. glabrata, C. krusei, C. kefyr, C. tropicalis, and many others, are common symbionts in the human gastrointestinal tract.

Taxonomic Classification for Candida

Kingdom: Fungi

Phylum: Ascomycota

Subphylum: Saccharomycotina

Class: Saccharomycetes (Hemiascomycetes)

Order: Saccharomycetales

Family: Saccharomycetaceae

Post Whole-Genome Duplication clade

Genus: Candida

Species:

C. glabrata

C. nivariensis

C. castelii

C. bracarensis

Pre-Whole Genome Duplication

KLE clade

C. kefyr

CTG clade

Family: Debaryomycetacae

C. africana

C. albicans

C. dubliniensis

C. famata

C. guilliermondii

C. metapsilosis

C. orthopsilosis

C. parapsilosis

C. tropicalis

Family: Metchnikowiaceae

C. auris

C. intermedia

C. lusitaniae

Methylotroph clade

Family: Pichiaeae

C. krusei

C. norvegensis

Some Candida spp. can move from their original site, invade underlying tissue, and cause an infectious disease. Most species fail to do so because the host’s immune system recognize and remove them before they establish an infection. As many as 30 Candida species can cause disease in humans.

All Candida spp. can exist in the yeast form and reproduce by budding, but some species (e.g., C. krusei and C. parapsilosis) can form “pseudohyphae” that consist of chains of budding cells that do not separate. Still other Candida species, such as C. albicans and C. tropicalis, can form “hyphae,” which are filamentous, branched, vegetative structures that elongate at their tips without budding.

The cell-walls of Candida species are a filigree of sugar polymers with proteins anchored to or entrapped within them. Cell wall-specific sugar polymers include chitin (2-6% by weight), which is chemically identical to the compound found in insect exoskeletons, linked to long chains of glucose collectively known as “β-glucans” (54-60% by weight). Cell wall-specific proteins include “GPI-linked proteins” that are anchored in the cell membrane by an assemblage of carbohydrates linked to membrane phospholipids, and other proteins linked to either β-glucans or “mannans” (polymers of the sugar mannose). Other cell wall proteins are bound to other proteins by means of disulfide bonds (-S-S-) or are associated with the cell wall by less specific means. Cell wall proteins include enzymes (e.g., chitinases, glucanases, trehalases, and others), adhesins, which allow the yeast cells to adhere to specific cells in the human body, cell wall assembly and maturation factors, and virulence factors that allow Candida to cause disease.

Deoxyribonucleic acid (DNA) sequence comparisons between pathogenic Candida have grouped them into four main groups: 1) the “CTG clade,” consists of organisms that use the codon CUG (CTG in DNA) to encode the amino acid serine rather than leucine and contains most pathogenic species of Candida (C. albicans, C. dubliniensis, C. tropicalis, C. parapsilosis, and others); 2) the “KLE clade,” whose genomes show no signs of having undergone wholesale duplication (C. kefyr); 3) the post-WGD group, whose genomes display wholesale duplication, and includes C. glabrata and those species closely related to it (C. castelii, C. bracarensis, and C. nivariensis); and 4) the Pichiaceae, which includes C. krusei and C. norvegensis.

The genomes of Candida spp. differ, as do their modes of reproduction. C. albicans normally contains eight chromosomes and members of the CTG clade typically have seven-eight chromosomes. Members of the post-WGD clade possess between eight-sixteen chromosomes. C. albicans and its close relatives (C. dubliniensis, C. tropicalis, C. parapsilosis, C. orthopsilosis, C. metapsilosis) are usually diploid (two copies of each chromosome) organisms, although variants with more or fewer chromosomes have been isolated. Candida reproduce asexually but modified sexual reproduction in which cells can exchange genetic material without undergoing meiosis (parasexual mating) has been observed in some members of the CTG clade. A few other Candida spp. (e.g., C. famata, C. krusei, C. guilliermondii, and others). that usually reproduce asexually can go through a normal fungal sexual cycle with meiosis, which results in haploid (one copy of each chromosome) spores (ascospores) born in a sac-like structure called an “ascus.” Several Candida species can only reproduce by asexual means (e.g., C. glabrata, C. parapsilosis, and others).

Pathogenicity and Clinical Significance

Candida spp. are usually opportunistic pathogens. Most of the time, they live with their hosts as commensals. The five Candida species most commonly associated with human disease (candidiasis) are C. albicans (65.3%), C. glabrata (11.3%), C. tropicalis (7.2%), C. parapsilosis (6.0%), and C. krusei (2.4%). There are over 30 species of Candida that can cause disease in human patients with compromised immune systems. Endogenous yeast populations in the mouth, throat, gastrointestinal tract, and vagina are usually held in check on the skin and in the digestive and reproductive systems by competing bacteria.

Healthy individuals can experience Candida infections (candidiasis). Vaginal candidiasis tends to occur in women who have recently taken antibiotics, are pregnant, use hormonal contraceptives, or have diabetes or a compromised immune system. The main symptoms are vaginal itching, pain or discomfort during urination or sexual intercourse, and an abnormal vaginal discharge. A less common infection in healthy persons is oral candidiasis (thrush), which may affect the oral cavity, throat, or esophagus. Babies less than one-month-old and adults who wear dentures, smoke, take antibiotics or inhaled corticosteroids, or have cancer, diabetes, a chronically dry mouth, or acquired immune deficiency syndrome (AIDS) are at risk for thrush. The main symptoms of thrush are white patches inside the mouth or throat, loss of taste, pain while eating or swallowing, cracking or redness at the corners of the mouth, and a cottony feeling, redness, or soreness in the mouth.

Suppression of the immune system allows fungal overgrowth and permits the invasion of deeper tissues. Patients who lack T-cell-mediated immunity (i.e. persons with DiGeorge syndrome, or severe combined immune deficiency syndrome) are at particularly high risk for developing chronic Candida infections, as are persons who take immunosuppressive drugs after transplants, or have AIDS. Chronic mucocutaneous candidiasis (CMC) refers to recurrent or persistent superficial infections of the skin, mucous membranes, and nails by Candida species. 60%-80% of CMC cases occur in infants and young children (mean age of onset is 3 years). Adult CMC cases are usually associated with thymus tumors (thymomas), bone marrow abnormalities, and myasthenia gravis. Invasive candidiasis is a serious infection in which the fungi penetrate underlying tissues and may infect multiple organs of the body. Untreated, systemic infections are always fatal.

Candidemia, a bloodstream infection with Candida, is a common infection in hospitalized patients. Approximately 8% of all nosocomial bloodstream infections are caused by Candida species. Patients in intensive care units (ICU) have the highest incidence of candidemia. Other risk factors for candidemia include the use of central venous catheters, total parenteral nutrition, broad-spectrum antibiotics, acute kidney failure, prior abdominal surgery, or abdominal perforation and/or leaks.

Magnified image of Candida albicans growing on cornmeal agar. Certain elements of the yeast are here identified. Photo by Y tambe via Wikimedia Commons.

Infect2e_p0192_1.jpg

In 2016, the United States Centers for Disease Control and Prevention (CDC) and Public Health England warned about the emergence of a multidrug-resistant Candida species, C. auris, which causes invasive health care-associated infections with high mortality rates. As of late September 2018, in the United States, more than 430 cases from 11 states had been reported.

Candida infections of the central nervous system most often involve the meningeal coverings of the brain and spinal cord (meningitis). Premature neonates and patients who have had neurosurgical procedures most often suffer from Candida meningitis. Patients who develop Candida CNS infections are often immunocompromised.

Drug Susceptibility

For candidal vaginitis, a host of over-the-counter agents are available, including clotrimazole (Gyne-Lotrimin), miconazole (Monistat), and tioconazole (Vagistat). Prescription agents include topical butoconazole (Gynazole), and terconazole (Terazole/Zazole), and oral fluconazole (Diflucan). Oral candidiasis is treated with either clotrimazole lozenges (Mycelex troche), miconazole mucoadhesive buccal tablets (Oravig), or liquid nystatin. If these treatments do not work, then oral Diflucan is prescribed. Diflucan is the treatment of choice for most cases of uncomplicated, noninvasive candidiasis, and CMC. If fluconazole is ineffective, then other azole drugs are used, beginning with itraconazole (Sporonox), then voriconazole (Vfend), and then posaconazole (Noxafil). Fungi do not have cholesterol in their membranes, but instead use a different sterol called ergosterol. Azole drugs inhibit ergosterol biosynthesis, which makes them relatively specific for fungi. However, liver function should be monitored in patients on azoles.

Another class of drugs that are effective against many Candida species is the echinocandin class, which inhibits β-glucan synthesis, and includes anidulafungin (Eraxis), caspofungin (Cancidas), and micafungin (Mycamine). All three echinocandins are available as parenteral medications, are effective against localized and systemic infections, and are the treatment of choice for candidemias.

The treatment of Candida infections of the central nervous system depends on the age of the patient. Adults are treated with an intravenous lipid formulation of amphotericin B, with or without oral flucytosine (Ancobon). Liposomal amphotericin B (AmBisome) gives higher concentrations in the brain compared with other formulations. Neonates are treated with amphotericin B deoxycholate (Fungizone), which is better tolerated by neonates. Flucytosine is too toxic for neonatal patients. Amphotericin B binds to ergosterol in fungal membranes and causes membrane leakage and cell death. Because amphotericin B also binds to cholesterol, this drug has severe adverse effects. Flucytosine interferes with DNA and RNA synthesis in fungal cells, and also has worrisome side effects.

C. krusei shows reduced susceptibility to amphotericin B and is intrinsically resistant to fluconazole but is usually susceptible to voriconazole and echinocandins.

Further Reading

1 

Bernard, H. & Oliver, K. (2018). Candida Species. In C. C. Kibbler, R. Barton, N. A. R. Gow, S. Howell, D. M. MacCallum, & R. J. Manuel (Eds.), Oxford Textbook of Medical Mycology (pp. 77-82). New York, NY: Oxford University Press.

2 

Center for Disease Control and Prevention. (2018, December 21). Recommendations for treatment of Candida auris. Retrieved from https://www.cdc.gov/fungal/candida-auris/c-auris-treatment.html.

3 

Dujon, B. A. & Louis E. J. (2017). Genome diversity and evolution in the budding yeasts (Saccharomycotina). Genetics, 206, 717-750.

4 

Pappas, P. G., Kauffman, C. A., Andes, D. R., Clancy, C. J., Marr, K. A., Ostrosky-Zeichner, L., … Sobel, J. D. (2016). Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clinical Infectious Diseases, 62(4), e1–e50, 2016. https://doi:10.1093/cid/civ933.

5 

Public Health England. (2018, September 21). Candidaemia: annual data from voluntary surveillance. Retrieved from https://www.gov.uk/government/publications/candidaemia-annual-data-from-voluntary-surveillance.

Web Sites of Interest

Microbiology and Immunology On-line: Mycology

http://pathmicro.med.sc.edu/book/mycol-sta.htm

National Candida Center

http://www.nationalcandidacenter.com

See also: AIDS; Antifungal drugs: Types; Bacterial vaginosis; Candidiasis; Fungi: Classification and types; Mouth infections; Oral transmission; Pathogens; Pelvic inflammatory disease; Skin infections; Thrush; Trichomonas; Urinary tract infections; Vaginal yeast infection; Women and infectious disease.

Citation Types

Type
Format
MLA 9th
Cheney Jr., Richard W. "Candida." Salem Health: Infectious Diseases & Conditions, 2nd Edition, edited by H. Bradford Hawley, Salem Press, 2020. Salem Online, online.salempress.com/articleDetails.do?articleName=Infect2e_0100.
APA 7th
Cheney Jr., R. W. (2020). Candida. In H. B. Hawley (Ed.), Salem Health: Infectious Diseases & Conditions, 2nd Edition. Salem Press. online.salempress.com.
CMOS 17th
Cheney Jr., Richard W. "Candida." Edited by H. Bradford Hawley. Salem Health: Infectious Diseases & Conditions, 2nd Edition. Hackensack: Salem Press, 2020. Accessed September 16, 2025. online.salempress.com.