Sporothrix schenckii

# Overview
Sporothrix schenckii is a fungus that can be found throughout the world. Areas characterized by warm, humid climates, are ideal for the fungus to thrive. The species is present in soil as well as in and on living and decomposing plant material such as peat moss. It can infect humans as well as animals and is the causative agent of sporotrichosis, commonly known as "rose handler's disease". Posttraumatic inoculation of S. schenckii is the typical method of infection. However, sporotrichosis may also develop as a result of spore inhalation, although this mode of transmission is infrequent. Infection commonly occurs in otherwise healthy individuals but is rarely life-threatening and can be treated with antifungals. In the environment, Sporothrix schenckii exists as a filamentous hyphae. In host tissue, S. schenckii thrives as a yeast. The transition from its hyphal form to yeast form is temperature dependent, making S. schenckii a thermally dimorphic fungus.

# Morphology
Sporothrix schenckii can be found in one of two morphologies, mold or yeast, making it a dimorphic fungus. The saprophytic form is found in the environment on plants and decaying matter. When the fungus infects a host, the yeast form predominates as a result of its temperature dependent morphology.

## Saprophytic/Hyphal Form
- At 25 C (77 F), in the environment or grown in the laboratory (in malt extract agar or potato dextrose agar), S. schenckii assumes its saprophytic stage.
- Macroscopically, colonies are characterized by apparent filaments, a smooth to leathery texture, and a finely wrinkled surface. Initially appearing off-white to creamy, the color may later become dark brown to black (dirty candle-wax color). Some strains are capable of growing darkly colored colonies from initial formation.
- Microscopically, composed of hyaline, hyphae are septate and approximately 1 to 2m in diameter. Arising from undifferentiated hyphae, conidiogenous cells form clusters of conidia on denticles. Conidia, which do not generate chains, are tear to clavate shaped and glass-like in appearance. They may be colorless or darkly colored. Conidia are sometimes referred to as resembling a flower.
Frequently, dark thick-walled conidia form adjacent to hyphae, and serve as a tool to distinguish S. schenckii from alternative, nonpathogenic species of Sporothrix.
- Frequently, dark thick-walled conidia form adjacent to hyphae, and serve as a tool to distinguish S. schenckii from alternative, nonpathogenic species of Sporothrix.

## Yeast
- At 37 C (98.6 F) either in a laboratory or in host tissue, S. schenckii assumes its yeast form.
- Macroscopically, the yeast form grows as smooth, white to tan colonies.
- Microscopically, yeast cells are 2 to 6m in diameter and have a round to oval shape. Typically, the cells appear to have elongated cigar-shaped buds stemming from a narrow origin. 

# Virulence Factors
Virulence factors of S. schenckii are the microbial characteristics that catalyze or augment microbial growth in host tissue.

## Melanin Production
- S. schenckii synthesizes melanin both in vitro and in vivo, meaning that both morphologies, yeast and mold, have the capacity to produce melanin.
- Melanin production is a virulence factor found in many pathogenic fungi and its production in S. schenckii protects the fungus from  oxidative stress as well as ultraviolet light and macrophage killing.
- Melanin has been shown to be synthesized using the 1,8-DHN pentaketide pathway.
- Melanization in S. schenckii is dependent on environmental factors such as, pH, temperature, and nutrient availability. Conidial menanization helps to enable the first stage of host infection, as it increases microbial resistance to macrophage phagocytosis.

## Adhesins
- Primary adhesion to extracellular matrix components and to epithelial and endothelial cells are necessary steps to effective pathogenesis.
- Both the yeast and conidia cells of S. schenckii display an increased ability to recognize and subsequently bind to extracellular matrix glycoproteins, fibronectin, type II collagen, and laminin, using separate receptors that are specific for these proteins.
- The fibronectin adhesions, which are found on the surface of yeast cells, are directly connected to virulence.
- S. schenckii  is capable of crossing intercellular space, enabling hematogenous dissemination.

## Proteases
- S. schenckii breaks down proteins by producing two separate proteases, a serine protease and an aspartic protease.
- These proteases appear to be essential for fungal growth, however, they have some functional overlap. The inactivation of either protein does not affect growth, but inactivation of both inhibits the fungus.
- Protease activity has been shown to be important in in vivo infection of mice. Substrates for these proteases include the skin proteins type-I collagen, stratum corneum, and elastin.

## Heat Tolerance
- Growing at host body temperature (37 C (98.6 F)) is an important requirement for pathogenesis.
- Strains of S. schenckii that are capable of growth at 35 C (95 F), but not 37 C (98.6 F), are only capable of causing the fixed cutaneous form of Sporotrichosis, as this form manifests with epidermal lesions (the skin is cooler than the body's interior).
- Strains that are able to thrive at 37 C (98.6 F) are responsible for lymphatic, disseminated, and extracutaneous/systematic forms of Sporotrichosis. 

# Immune Response
Infection by S. schenckii is generally self-limiting in immunocompetent hosts. The immune response prevents fungal dissemination and is the reason that most Sporothrix infections are cutaneous.

## Innate
The yeast form of S. schenckii is effectively phagocytosed by cells of the innate immune system and are recognized based on the sugars displayed on their surface or lipids in the yeast cell membrane. Although they are taken up, they are not efficiently killed. It is hypothesized that ergosterol peroxide reacts with and detoxifies reactive oxygen species generated by the respiratory burst used by phagocytes to kill cells they have ingested. S. schenckii is also capable of modulating the immune response to promote its own survival by blocking cytokine production by macrophages.

## Specific
The specific immune response becomes active at later stages of infection and involves both B cells and T cells. Severe sporotrichosis is rare in endemic areas where humans are in near constant contact with S. schenckii spores. This fact, combined with the increased severity of disease in immunocompromised patients, suggests an important role for specific immunity in S. schenckii infection. Patients with sporotrichosis have been shown to produce antibodies specific to S. schenckii and these antibodies may actually be protective against the disease.

## Culture and Identification