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CANDIDA Species


Taxonomic Classifications

Kingdom: Fungi
Phylum: Ascomycota
Subphylum: Ascomycotina
Class: Ascomycetes
Order: Saccharomycetales
Family: Saccharomycetaceae
Genus: Candida

 

Candida species are yeast-like fungi that form moist, pasty, and usually white colonies. Spores are produced along the easily fragmented filaments and become so numerous that the filaments can be entirely obscured. the spores can reproduce themselves by "budding". The species are common in soil and organic debris and can also cause human disease. Holomorphs: Hyphopichia, Issatchenkia, Metschnikowia, Saccharomycopsis, Stephanoascus.
(Source: http://www.botany.utoronto.ca)

 

On Sabouraud's dextrose agar colonies are white to cream colored, smooth, glabrous and yeast-like in appearance. Microscopic morphology shows spherical to subspherical budding yeast-like cells or blastoconidia, 2.0-7.0 x 3.0-8.5 um in size. (Source: http://www.mycology.adelaide.edu.au)

Description and Habitats

Candida is a yeast-like fungi, which is normally present in the bowel. It feeds on sugars, simple carbohydrates and fermented products like alcohol and cheese. Everyone has candida in the gut but the problem with it only occurs when the numbers gets out of control. Causes for this can be: too many antibiotics, a hormone imbalance (the pill is a major factor in this) stress and poor nutrition. These affect the balance of organisms in the gut and allow the bad ones to multiply.

Candida proliferates in the intestines, it can change its anatomy and physiology from the yeast-like form to the mycelial fungal form. It is well recognized that Candida albicans is a dimorphic (two shapes and forms) organism and as such can exist in these two states. The yeast-like state in a non-invasive, sugar-fermenting organism, whereas the fungal state produces rhizoids, or very long root-like structures, which can penetrate the mucosa, and it is invasive.

Species

The genus Candida includes around 154 species. Among these, six are most frequently isolated in human infections. While Candida albicans is the most abundant and significant species, Candida tropicalis, Candida glabrata, Candida parapsilosis, Candida krusei, and Candida lusitaniae are also isolated as causative agents of Candida infections. Importantly, there has been a recent increase in infections due to non-albicans Candida spp., such as Candida glabrata and Candida krusei. Patients receiving fluconazole prophylaxis are particularly at risk of developing infections due to fluconazole-resistant Candida krusei and Candida glabrata strains.

Species Commonly Causing Invasive Candidiasis

Candida ablicans

  • Germ tube positive
  • Creamy colonies, as other yeasts
  • May display pseudohyphae and true hyphae
  • Most commonly isolated candidiasis
  • Virulence factors include rapid germination within tissue, protease production, surface integrin-like molecules for binding extracellular matrix, complement protein binding receptor, phenotypic switching, and surface variation and hydrophobicity.

candida albicans
Candida albicans in the cerebrospinal fluid of a patient with a malfunctioning ventriculoperitoneal shunt.

candida albicans
Candida albicans on blood agar; moist, opaque colonies are characteristic of yeast.


Candida tropicalis

  • May cause infection, especially of the immunocompromised; may also be isolated
    without evidence of disease
  • Creamy colonies with mycelial fringe
  • Blastoconidia arise singly or in small groups anywhere along long pseudohyphae


Candida parapsilosis

  • Relatively frequent cause of candidal endocarditis
  • Creamy colonies; sometime with lacy appearance
  • Blastoconidia arise singly or in small groups anywhere along pseudohyphae;
    at low power has characteristic shaggy star appearance
  • At high power, crooked or curved, short pseudohyphae and occasional large
    hyphal elements (termed "giant cells") can be seen

candida parapsilosis
Low power appearance of Candida parapsilosis on Dalmau plate.
Note the characteristic "shaggy star" morphology

The above mycological photo and caption came from  this website: http://pangloss.ucsfmedicalcenter.org

Health Effects

The Wadsworth Center of New York State, Department of Health reported, that members of the genus Candida are found in all areas of the intestinal tract, usually causing no medical problems. However, in patients with a compromised immune system, life threatening diseases may result. In the past two decades Candida species have become the fifth most common cause of hospital-acquired bloodstream infections. Advances in immunosuppression for organ transplants and cancer therapy has increased the susceptible population as has the advent of such diseases as AIDS which specifically target the immune system. Not only do these infections result in increased hospital stays, but they have become a significant cause of mortality in immunocompromised patients.

Pregnant women produce vaginal secretions with altered levels of glycogen.  This encourages the growth of Candida, and vaginal candidiasis is common in pregnant women. Their husbands sometimes contract candida balanitis, a nasty infection of the penis, though this may also be a consequence of diabetes.  If cutaneous candidiasis becomes chronic, it may be a sign of various abnormalities of the thymus, of the thyroid, of white blood cells (leucocytes), or be a symptom of AIDS. [from Bryce Kendrick, The Fifth Kingdom]

The Microbiology and Immunology Online of University of South Carolina states that Candida albicans is an endogenous organism. It can be found in 40-80% of normal human beings. It is present in the mouth, gut, and vagina. It may be present as a commensal or a pathogenic organism. Infections with Candida usually occur when a patient has some alteration in cellular immunity, normal flora or normal physiology. Patients with decreased cellular immunity have decreased resistance to fungal infections. Prolonged antibiotic or steroid therapy destroys the balance of normal flora in the intestine allowing the endogenous Candida to overcome the host. Invasive procedures, such as cardiac surgery and indwelling catheters, produce alterations in host physiology and some of these patients develop Candida infections. Although it most frequently infects the skin and mucosae, Candida can cause pneumonia, septicemia or endocarditis in the immuno-compromised patient. The establishment of infection with Candida species appears to be a property of the host - not the organism. The more debilitated the host, the more invasive the disease.

Macroscopic and Microscopic Features

The colonies of Candida spp. are cream colored to yellowish, grow rapidly and mature in 3 days. The texture of the colony may be pasty, smooth, glistening or dry, wrinkled and dull, depending on the species.

The microscopic features of Candida spp. also show species-related variations. All species produce blastoconidia singly or in small clusters. Blastoconidia may be round or elongate. Most species produce pseudohyphae which may be long, branched or curved. True hyphae and chlamydospores are produced by strains of some Candida spp.

Although they are the members of the same genus, the various species do have some degree of unique behavior with respect to their colony texture, microscopic morphology on cornmeal tween 80 agar at 25C (Dalmau method) and fermentation or assimilation profiles in biochemical tests.

Candida albicans

* Colony morphology

Candida albicans strains produce white to cream colored, pasty, smooth colonies on Sabouraud dextrose agar. On phloxine B agar plates, six different colony phenotypes (smooth, fuzzy, irregular, star, ring, and stipple) are observed. Significantly, fluconazole MICs of the stipple phenotype were found to be consistently high.

* Microscopic morphology

This can best be visualized when the test isolate is incubated on cornmeal tween 80 agar and at 25C for 72 h. Candida albicans produces clusters of round blastoconidia along the hyphae and particularly at points of septa. Pseudohyphae and true hyphae are also observed. Candida albicans, together with Candida dubliniensis, are the two Candida spp. which produce a typical asexual spore, chlamydoconidium. Chlamydoconidia are round, large, thick-walled and usually terminal. Candida albicans produces no surface growth when inoculated in Sabouraud broth.

Germ tube production is the other typical characteristic of this species. Germ tube is the beginning of true hyphae and observed by microscopic examination upon inoculation of the strain in serum. Similar to the chlamydoconidia production, the two Candida spp. that produce germ tube are Candida albicans and Candida dubliniensis. As will be discussed in the page on Candida dubliniensis , investigations on simple methods, as well as molecular studies are on the way to differentiate these two species. In the interim, in routine laboratory work, a strain that produces germ tube and chlamydoconidia is defined as Candida albicans.

Candida stellatoidea, once accepted to be a separate Candida species, is now classified as a subspecies of Candida albicans which differs from Candida albicans by not assimilating sucrose and not being resistant to cycloheximide.

Candida tropicalis

* Colony morphology

On Sabouraud dextrose agar, Candida tropicalis colonies are cream-colored with a slightly mycelial border. It may produce a thin surface film and bubbles when grown in Sabouraud broth.

* Microscopic morphology

On cornmeal tween 80 agar and at 25C after 72 h, it produces oval blastospores which are located along the long pseudohyphae. The blastospores may appear singly or in clusters. The pseudohyphae branch abundantly. Candida tropicalis may also produce true hyphae

Candida parapsilosis

* Colony morphology

Candida parapsilosis colonies are white, creamy, shiny, and smooth or wrinkled on Sabouraud dextrose agar. It does not grow on the surface when inoculated into Sabouraud broth.

* Microscopic morphology

On cornmeal tween 80 agar and at 25C after 72 h, it produces blastospores which are located along the pseudohyphae. Typically, the pseudohyphae may be curved and large mycelial (hyphal) elements which are called "giant cells" may be observed.

Laboratory Precautions

No special precautions other than general laboratory precautions are required.

Susceptibility

In Vitro Susceptibility

Amphotericin B and other polyenes

NCCLS method is yet insufficient in discrimination of amphotericin B-resistant isolates from the susceptible ones, primarily due to the narrow range of MICs that it generates for all test strains. Modifications of this method, such as the use of Antibiotic Medium 3 supplemented to 2% glucose (AM3) instead of the reference RPMI 1640 medium, and use of 24 h incubation instead of the standard 48 h readings, have yielded inconsistent results in various investigators' hands. While efforts to develop a novel relevant methodology for amphotericin B susceptibility testing are in progress, amphotericin B has proven to be fungicidal against Candida strains. Liposomal nystatin appeared active in vitro against some of the isolates with relatively high amphotericin B MICs.

Azoles and Allylamines

In vitro resistance to azoles is observed in various Candida spp. While Candida krusei is intrinsically resistant to fluconazole, Candida glabrata may be susceptible, dose-dependent susceptible, or resistant. Other species, such as Candida inconspicua and Candida tropicalis may also generate high fluconazole MIC. In systemic infections, fluconazole-resistant Candida albicans isolates are rare but do exist. On the other hand, patients with AIDS receiving fluconazole prophylaxis are particularly under risk to develop infections due to fluconazole-resistant Candida albicans. Genetic mechanisms involved in multidrug resistance of Candida albicans have recently been explore. Multidrug efflux pumps have been shown to be involved in fluconazole resistance in Candida albicans and Candida tropicalis. Mutation in sterol 14-demethylase P450 enzyme may also lead to azole resistance.

The most striking feature of itraconazole is its favorable in vitro activity against some of the fluconazole-resistant Candida strains. This property, as well as the availability of its parenteral formulation, now makes itraconazole a good candidate for treatment of systemic Candida infections. However, there is definitely cross-resistance between fluconazole and itraconazole remains relevant for a subset of Candida isolates, such as some Candida glabrata strains. Terbinafine, in combination with fluconazole and itraconazole may also yield enhanced in vitro activity against some azole-resistant Candida albicans strains. Candida lipolytica and Candida pelliculosa, on the other hand, generate high itraconazole MICs in general.

The novel triazoles have favorable in vitro activity against most Candida spp. Although voriconazole MICs are relatively high against Candida guilliermondii and Candida krusei, a recent animal study of therapy of C. krusei infections suggested good activity. Posaconazole (SCH56592) MICs in general appear low.

Flucytosine

While flucytosine is effective but now less commonly used against Candida infections, strains which are primarily resistant to flucytosine  or develop resistance during therapy have been identified.

Glucan Synthesis Inhibitors (Echinocandins)

In vitro data obtained so far against Candida for these novel agents are promising. Agents of this class are active and often appear fungicidal against both fluconazole-resistant and -susceptible isolates. Isolates of Candida parapsilosis consistently have elevated MICs, but the relevance of this is unclear.

In Vivo Efficacy

Amphotericin B, fluconazole, and itraconazole in general show favorable activity in vivo in treatment of Candida infections. Itraconazole alone, as well as itraconazole and flucytosine combination, proved to have good long term therapeutic efficacy in esophageal candidiasis in AIDS patients. Importantly and in general, improvement of unfavorable immune factors constitutes the major issue in successful clinical outcome of Candida infections. Removal of the predisposing medical devices, such as catheters or shunts are frequently required for clinical cure. Nevertheless, failure despite appropriate therapy with the agent that appears active in vitro, such as amphotericin B or fluconazole, may be observed. Ketoconazole is now less commonly used in treatment of Candida infections due to the availability of more efficacious and less toxic azole compounds.

The echinocandins in development, caspofungin and FK463 appear promising in treatment of oropharyngeal and esophageal candidiasis.

Although use of fluconazole might be beneficial for secondary prophylaxis in patients with AIDS who have recovered from the primary attack of esophageal candidiasis, the potential risk of emergence of fluconazole resistance [or appearance of candidiasis due to fluconazole-resistant species remains. Similarly, fluconazole prophylaxis following bone marrow transplantation has limited activity against some non-albicans Candida spp. and no activity against filamentous fungi.

The mycological information gathered and organized in this extensive research on the
different Pathogenic Molds was  sourced out from the list of websites below:

http://www.osha.gov | http://www.doctorfungus.org | http://www.mycology.adelaide.edu.au
http://www.mycology.net | http://www.dehs.umn.edu | http://www.mold-help.org | http://www.mycology.net
http://www.pfdb.net | http://www.clinical-mycology.com | http://www.botany.utoronto.ca | http://www.med.sc.edu
http://www.tigr.org | http://www.pangloss.ucsfmedicalcenter.org | http://www.dermnz.org | http://ncbi.nlm.nih.gov
http://www.wadsworth.org |
http://botit.botany.wisc.edu

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