II: FUNGI

B. YEAST

Fundamental Statements for this Learning Object:

1. Yeasts are eukaryotic unicellular fungi
2. Some yeast are dimorphic in that they can grow as an oval, budding yeast, but under certain culture conditions, they may produce filament-like structures called hyphae similar to molds.
3. Components of the yeast cell wall that function as pathogen-associated molecular patterns or PAMPs include lipoteichoic acids, zymosan, and mannose-rich glycans.
4. These PAMPs bind to pattern-recognition receptors or PRRs on a variety of body defense cells and triggers innate immune defenses.
5.
Cell wall molecules can also trigger adaptive immunity such as the production of antibody molecules against bacterial cell wall antigens.
6.
Yeasts reproduce asexually by a process called budding.
7. Candida albicans is found as normal flora on the mucous membranes and in the gastrointestinal tract but is usually held in check by the body’s normal microbiota and normal body defenses.
8. Candida can cause a variety of opportunistic infections in people who are debilitated, immunosuppressed, or have received prolonged antibacterial therapy, and infect the lungs, blood, heart, and meninges, especially in the compromised or immunosuppressed host.
9. Cryptococcus neoformans infections are usually mild or subclinical but, when symptomatic, usually begin in the lungs after inhalation of the yeast in dried bird feces.
10. Pneumocystis jiroveci can cause a severe pneumonia called PCP (Pneumocystis pneumonia).
11. Malassezia globosa is  the most frequent cause of a superficial skin infection called tinea versicolor and also the most common cause of dandruff.

 

LEARNING OBJECTIVES FOR THIS SECTION


Mycology (def) is the study of fungi. Fungi include yeasts, molds, and fleshy fungi. They:

1. are eukaryotic;
2. have a rigid cell wall;
3. are chemoheterotrophs (organisms that require organic compounds for both carbon and energy sources);
4. obtain their nutrients by absorption;
5. obtain nutrients as saprophytes, organisms that live off of decaying matter, or as parasites, organisms that live off of living matter.

We will be concerned mainly with the yeasts and molds, especially those causing mycoses (fungal infections).

In this section we will look at yeasts.


Yeasts

    A. Yeast Morphology

    1. Yeast (def) (see Fig. 1) are unicellular fungi which usually appear as oval cells 1-5 µm wide by 5-30 µm long.

    2. They have typical eukaryotic structures (see Fig. 2).

    3. They have a thick polysaccharide cell wall.

    4. They are facultative anaerobes (def).

    5. The yeast Candida is said to be dimorphic (def)in that it can grow as an oval, budding yeast, but under certain culture conditions, the budding yeast may elongate and remain attached producing filament-like structures called pseudohyphae (def). C. albicans may also produce true hyphae (def) similar to molds (see Fig. 3). In this case long, branching filaments lacking complete septa form. The pseudohyphae and hyphae help the yeast to invade deeper tissues after it colonizes the epithelium. Asexual spores called blastoconidia (blastospores) develop in clusters along the hyphae, often at the points of branching. Under certain growth conditions, thick-walled survival spores called chlamydoconidia (chlamydospores) may also form at the tips or as a part of the hyphae (see Fig. 4.)

     

B. The Role of Fungal Cell Wall Components in Initiating Body Defense

Initiation of innate immunity

In order to protect against infection, one of the things the body must initially do is detect the presence of microorganisms. The body does this by recognizing molecules unique to microorganisms that are not associated with human cells. These unique molecules are called pathogen-associated molecular patterns or PAMPs (def). (Because all microbes, not just pathogenic microbes, possess PAMPs, pathogen-associated molecular patterns are sometimes referred to as microbe-associated molecular patterns or MAMPs.)

Components of the yeast cell wall that function as PAMPs include lipoteichoic acids, and zymosan. In addition, bacteria and other microorganisms also possess  mannose-rich glycans (short carbohydrate chains with the sugar mannose or fructose as the terminal sugar) that function as PAMPs. These mannose-rich glycans are common in microbial glycoproteins and glycolipids but rare in those of humans. These PAMPs bind to pattern-recognition receptors (def) on a variety of defense cells of the body and triggers innate immune defenses such as inflammation (def), fever, and phagocytosis.

    by Gary E. Kaiser, Ph.D.
    Professor of Microbiology, The Community College of Baltimore County, Catonsville Campus
    This work is licensed under a Creative Commons Attribution 4.0 International License.
    Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html.

    Creative Commons License

    Last updated: August, 2019
    Please send comments and inquiries to Dr. Gary Kaiser

     

Yeast cell wall components also activate the alternative complement pathway and the lectin pathway, defense pathways that play a variety of roles in body defense.

 

Initiation of adaptive immunity

Cell wall molecules can also trigger adaptive immunity such as the production of antibody molecules against bacterial cell wall antigens. An antigen is defined as a substance that reacts with antibody molecules and antigen receptors on lymphocytes. An immunogen is an antigen that is recognized by the body as non-self and stimulates an adaptive immune response.

The body recognizes an antigen as foreign when epitopes of that antigen bind to B-lymphocytes (def) and T-lymphocytes (def) by means of epitope-specific receptor molecules having a shape complementary to that of the epitope. The epitope receptor on the surface of a B-lymphocyte is called a B-cell receptor and is actually an antibody molecule. The receptor on a T-lymphocyte is called a T-cell receptor (TCR).

 

C. Reproduction of yeasts

    1. Yeasts reproduce asexually by a process called budding (see Fig. 1 and Fig. 5). A bud is formed on the outer surface of the parent cell as the nucleus divides. One nucleus migrates into the elongating bud. Cell wall material forms between the bud and the parent cell and the bud breaks away.

    2. A few yeasts, such as Candida albicans, also produce clusters of asexual reproductive spores called blastoconidia (blastospores) (def) and thick-walled survival spores called chlamydoconidia (chlamydospores) (def) ; see Fig. 4.

    3. Yeasts can also reproduce sexually by means of sexual spores called ascospores which result from the fusion of the nuclei from two cells followed by meiosis (def). Sexual reproduction is much less common than asexual reproduction but does allow for genetic recombination (def).

     

    D. Yeast infections

    1. Candida albicans

    Candida albicans is found as normal flora on the mucous membranes and in the gastrointestinal tract but is usually held in check by:

    a) normal flora bacteria; and
    b) normal body defenses.

    Candida can cause a variety of opportunistic infections in people who are debilitated, immunosuppressed, or have received prolonged antibacterial therapy. Women who are diabetic, pregnant, taking oral contraceptives, or having menopause are also more prone to vaginitis. These conditions alter the sugar concentration and pH of the vagina making it more favorable for the growth of Candida. People who are immunosuppressed frequently develop thrush, vaginitis, and sometimes disseminated infections.

    Any Candida infection is called candidiasis. Candida most commonly causes vaginitis (def) (see Fig. 6 and Fig. 6A); thrush (def) (an infection of the mouth) (see Fig. 7 and Fig. 7A); balantitis (def) (an infection of the foreskin and head of the penis) (see Fig. 8); onchomycosis (def) (an infection of the nails) (see Fig. 9); and dermatitis (def) (diaper rash and other infections of moist skin). Less commonly, Candida can infect the lungs, blood, heart, and meninges (def), especially in the compromised or immunosuppressed host. Candida now causes about 10% of all cases of septicemia (def). Candidiasis of the esophagus, trachea, bronchi, or lungs, in conjunction with a positive HIV antibody test, is one of the indicator diseases for AIDS.

    Candida is said to be dimorphic, that is it has two different growth forms. It can grow as an oval, budding yeast, but under certain culture conditions, the budding yeast may elongate and remain attached producing filament-like structures called pseudohyphae (see Fig. 10). C. albicans may also produce true hyphae (see Fig. 3) similar to molds. In this case long, branching filaments lacking complete septa form. The pseudohyphae and hyphae help the yeast to invade deeper tissues after it colonizes the epithelium. Asexual spores called blastoconidia are reproductive units produced by budding in yeasts. Under certain growth conditions, thick-walled survival spores called chlamydoconidia (def) may also form at the tips or as a part of the hyphae (see Fig. 5)

    The most common Candida species causing human infections is C. albicans, causing 50-60% of all Candida infections. Candida glabrata is second, causing 15-20% of Candida infections; Candida parapsilosis is third, responsible for 10-20%. More recently, Candida auris has been causing relatively rare but severe infections in patients that have been hospitalized for long periods of time, sometimes entering the bloodstream causing invasive infections throuout the body. C. auris is often resistant to common antifungal drugs and kills as many as 1 out of 3 patients with invasive infections.

    2. Cryptococcus neoformans

    A lesser known but often more serious pathogenic yeast is Cryptococcus neoformans. Like many fungi, this yeast can also reproduce sexually and the name given to the sexual form of the yeast is Filobasidiella neoformans. It appears as an oval yeast 5-6 µm in diameter, forms buds with a thin neck, and is surrounded by a thick capsule (see Fig. 11). It does not produce pseudohyphae and chlamydospores. The capsule enables the yeast to resist phagocytic engulfment. The yeast is dimorphic. In its sexual form, as well as in its asexual form under certain conditions, it can produce a hyphal form.

    Cryptococcus infections are usually mild or subclinical but, when symptomatic, usually begin in the lungs after inhalation of the yeast in dried bird feces. It is typically associated with with pigeon and chicken droppings and soil contaminated with these droppings. Cryptococcus, found in soil, actively grows in the bird feces but does not grow in the bird itself. Usually the infection does not proceed beyond this pulmonary stage. In the immunosuppressed host, however, it may spread through the blood to the meninges and other body areas, often causing cryptococcal meningoencephalitis. Any disease by this yeast is usually called cryptococcosis.

    Dissemination of the pulmonary infection can result in a very severe and often fatal cryptococcal meningoencephalitis. Cutaneous and visceral infections are also found. Although exposure to the organism is probably common, large outbreaks are rare, indicating that an immunosuppressed host is usually required for the development of severe disease. Extrapulmonary cryptococcosis, in conjunction with a positive HIV antibody test, is another indicator disease for AIDS.

    3. Pneumocystis jiroveci

    Pneumocystis jiroveci (formerly called Pneumocystis carinii) (see Fig. 7 and Fig. 8) is thought to be transmitted from person to person by the respiratory route and is almost always asymptomatic. However, in persons with highly depressed immune responses, such as people with leukemias or infected with the Human Immunodeficiency Virus (HIV), P. jiroveci can cause a severe pneumonia called PCP (Pneumocystis pneumonia).

    P. jiroveci can be found in 3 distinct morphologic stages:

    • The trophozoite (trophic form), a haploid amoeboid form 1-4 µm in diameter that replicates by mitosis and binary fission. The trophic forms are irregular shaped and often appears in clusters.
    • A precystic form or early cyst. Haploid trophic forms conjugate and produce a zygote or sporocyte (early cyst). 
    • The cyst form, which contains several intracystic bodies or spores are 5-8 µm in diameter. It has been postulated that in formation of the cyst form (late phase cyst), the zygote undergoes meiosis and subsequent mitosis to typically produce eight haploid ascospores (sporozoites) (see Fig. 12). As the haploid ascospores are released the cysts often collapse forming crescent-shaped bodies (see Fig. 12A). P. jiroveci is usually transmitted by inhalation of the cyst form. Released ascospores then develop into replicating trophic forms that attach to the wall of the alveoli and replicate to fill the alveoli.
    • Proposed life cycle for Pneumocystis jiroveci.

    In biopsies from lung tissue or in tracheobronchial aspirates, both a trophic form about 1-4 µm in diameter with a distinct nucleus and a cyst form between 5-8 µm in diameter with 6-8 intracystic bodies (ascospores) can be seen.

    4. Malassezia globosa

    Malassezia globosa is a (see Fig. 13) dimorphic yeast that is the most frequent cause of a superficial skin infection called tinea versicolor that commonly appears as a hypopigmentation of the infected skin. M. globosa is also the most common cause of dandruff and seborrheic dermatitis. The yeast is naturally found on the skin.

     

     

     

    Medscape article on infections associated with organisms mentioned in this Learning Object. Registration to access this website is free.

 


Gary E. Kaiser, Ph.D.
Professor of Microbiology
The Community College of Baltimore County, Catonsville Campus
This work is licensed under a Creative Commons Attribution 4.0 International License.
Based on a work The Grapes of Staph at https://cwoer.ccbcmd.edu/science/microbiology/index_gos.html.

Creative Commons License

Last updated: Feb., 2020
Please send comments and inquiries to Dr. Gary Kaiser