Cryptococci and Cryptococcosis

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Cryptococci and cryptococcosis

Cryptococcus is a yeast that has a capsule surrounding the cell. In the yeast classification system, Cryptococcus is a member of the Phylum Basidimycota, Subphylum Basidimycotina, Order Sporidiales, and Family Sporidiobolaceae.

There are 37 species in the genus Cryptococcus. One of these, only one species is disease-causing, Cryptococcus neoformans. There are three so-called varieties of this species, based on antigenic differences in the capsule, some differences in biochemical reactions such as the use of various sugars as nutrients, and in the shape of the spores produced by the yeast cells. The varieties are Cryptococcus neoformans var. gatti, grubii, and neoformans. The latter variety causes the most cryptococcal infections in humans.

Cryptococcus neoformans has a worldwide distribution. It is normally found on plants, fruits and in birds, such as pigeons and chicken. Transmission via bird waste is a typical route of human infection.

Cryptococcus neoformans causes an infection known as cryptococcosis. Inhalation of the microorganism leads to the persistent growth in the lungs. For those whose immune system is compromised, such as those having Acquired Immunodeficiency Syndrome (AIDS ), the pulmonary infection can be life-threatening. In addition, yeast cells may become distributed elsewhere in the body, leading to inflammation of nerve lining in the brain (meningitis ). A variety of other infections and symptoms can be present, including infections of the eye (conjunctivitis), ear (otitis), heart (myocarditis), liver (hepatitis ), and bone (arthritis).

The most common illness caused by the cryptococcal fungus is cryptococcal meningitis. Those at most risk of developing cryptococcosis are AIDS patients. Those who have received an organ, are receiving chemotherapy for cancer or have Hodgkin's disease are also at risk, since frequently their immune systems are suppressed. As the incidence of AIDS and the use of immunosupressant drugs have grown over the past decade, the number of cases of cryptococcosis has risen. Until then, cases of cryptococcus occurred only rarely. Even today, those with a well-functioning immune system are seldom at risk for cryptococcosis. For these individuals a slight skin infection may be the only adverse effect of exposure to Cryptococcus.

Cryptococcus begins with the inhalation of Cryptococcus neoformans. Likely, the inhaled yeast is weakly encapsulated and is relatively small. This allows the cells to penetrate into the alveoli of the lungs. There the production of capsule occurs. The capsule surrounding each yeast cell aids the cell in avoiding the immune response of the host, particularly the engulfing of the yeast by macrophage cells (which is called phagocytosis ). The capsule is comprised of chains of sugars, similar to the capsule around bacteria . The capsule of Cryptococcus neoformans is very negatively charged. Because cells such as macrophages are also negatively charged, repulsive forces will further discourage interaction of macrophages with the capsular material.

Another important virulence factor of the yeast is an enzyme called phenol oxidase. The enzyme operates in the production of melanin. Current thought is that the phenol oxidase prevents the formation of charged hydroxy groups, which can be very damaging to the yeast cell. The yeast may actually recruit the body's melanin producing machinery to make the compound.

Cryptococcus neoformans also has other enzymes that act to degrade certain proteins and the phospholipids that make up cell membranes. These enzymes may help disrupt the host cell membrane, allowing the yeast cells penetrate into host tissue more easily.

Cryptococcus neoformans is able to grow at body temperature. The other Cryptococcus species cannot tolerate this elevated temperature.

Yet another virulence factor may operate. Evidence from laboratory studies has indicated that antigens from the yeast can induce a form of T cells that down regulates the immune response of the host. This is consistent with the knowledge that survivors of cryptococcal meningitis display a poorly operating immune system for a long time after the infection has ended. Thus, Cryptococcus neoformans may not only be capable of evading an immune response by the host, but may actually dampen down that response.

If the infection is treated while still confined to the lungs, especially in patients with a normally operative immune system, the prospects for full recovery are good. However, spread to the central nervous system is ominous, especially in immunocompromised patients.

The standard treatment for cryptococcal meningitis is the intravenous administration of a compound called amphotericin B. Unfortunately the compound has a raft of side effects, including fever, chills, headache, nausea with vomiting, diarrhea, kidney damage, and suppression of bone marrow. The latter can lead to a marked decrease in red blood cells. Studies are underway in which amphotericin B is enclosed in bags made of lipid material (called liposomes). The use of liposomes can allow the drug to be more specifically targeted to the site where treatment is most needed, rather than flooding the entire body with the drug. Hopefully, the use of liposome-delivered amphotericin B will lessen the side effects of therapy.

See also Fungi; Immunomodulation; Yeast, infectious