| Sporothrix schenckii | |
|---|---|
 | |
| Conidiophores and conidia | |
Scientific classification | |
| Domain: | Eukaryota |
| Kingdom: | Fungi |
| Division: | Ascomycota |
| Class: | Sordariomycetes |
| Order: | Ophiostomatales |
| Family: | Ophiostomataceae |
| Genus: | Sporothrix |
| Species: | S. schenckii |
| Binomial name | |
| Sporothrix schenckii Hektoen & C.F.Perkins (1900) | |
Sporothrix schenckii, afungus that can be found worldwide in the environment, is named for medical student Benjamin Schenck, who in 1896 was the first to isolate it from a human specimen.[1] Thespecies is present in soil as well as in and on living and decomposing plant material such aspeat moss. It can infect humans as well as animals and is the causative agent ofsporotrichosis, commonly known as "rose handler's disease."[2] The most common route of infection is the introduction ofspores to the body through a cut or puncture wound in the skin. Infection commonly occurs in otherwisehealthy individuals but is rarely life-threatening and can be treated withantifungals. In the environment it is found growing as filamentoushyphae. In host tissue it is found as ayeast. The transition between the hyphal and yeast forms is temperature dependent makingS. schenckii athermally dimorphic fungus.[1]
Sporothrix schenckii can be found in one of twomorphologies, hyphal or yeast. The hyphal form is found in the environment on plants and decaying matter. When the fungus makes the transition into a host, the yeast morphology predominates.
When in the environment or grown in the laboratory at 25 °C (77 °F)S. schenckii assumes its hyphal form.[5] Macroscopically, filaments are apparent and colonies are moist, leathery to velvety, and have a finely wrinkled surface. The colour is white initially and may change color over time to become cream to dark brown ("dirty candle-wax" color).[1] Microscopically, hyphae areseptate approximately 1 to 2 μm in diameter.Conidia are oval shaped and glass like (hyaline) in appearance. They may be colorless or darkly colored. Conidia are sometimes referred to as resembling a flower.[6]
At 37 °C (99 °F) either in the laboratory or in host tissue,S. schenckii assumes its yeast form.Macroscopically, the yeast form grows as smooth white or off-white colonies. Microscopically, yeast cells are 2 to 6 μm long and show an elongated cigar-shaped morphology.[1]
S. schenckii has a worldwide distribution[1] but certain areas of the world includingPeru, have a higher incidence of disease.[7] Based onsequence analysis[8] it has been found thatS. schenckii isolates can be placed inphylogenetic groups that reflect the region from which they were isolated.S. schenckii is often isolated from plants and associated packing material.[9]Gardeners,[10]landscapers,[11] andforesters[9] are at high risk of infection.Sporothrix infection can also be transmitted by cat bites or scratches. This mode of transmission has been responsible for epidemics of sporotrichosis.[12]Immunocompromised individuals are at increased risk of infection and such patients often exhibit more severe forms of disease.[13][14][15]
S. schenckii most commonly enters the body through minor trauma that compromises theskin barrier.[13] It is this route of infection, coupled with its presence onroses that give sporotrichosis its common name of "rose-handler's disease"[16] or "rose thorn disease".[17] Inhalation of spores is a rare route of infection largely associated with immunocompromised hosts.[18]
Thecutaneous form of disease is caused by introduction ofS. schenckii into the body through disruption of the skin barrier.[13] The first symptom of cutaneous sporotrichosis is a small skinlesion. These lesions may showulceration and/orerythema.[1] Commonly, infection spreads through thelymph alonglymphatic vessels and causes lymphocutaneous sporotrichosis. This form of disease is characterized by the appearance of lesions at sites distant to the initial infection.[1] Infection can occur in nonhuman animals and may be transmitted to humans through contact.Veterinarians are at particularly high risk of contracting disease from animals (zoonotic infection).[19]
Disseminated disease occurs when the fungus spreads throughout the body. Found only in immunocompromised patients,[1][14][18] it is a very severe condition. When infection becomes disseminated,S. schencki can afflict joints, the brain, and the spine.[1] Patients with this condition must be treated aggressively withantifungals and may remain onprophylactic antifungal drugs for life to prevent recurrence or reinfection.[13]
Sporothrix infection presents macroscopically with nonspecificsymptoms.[20] In the clinical laboratory, many fungi isolated in culture are disregarded ascontaminants.[21] Therefore, accurate patient histories are important[2] to establish suspicion of sporotrichosis and to inform which diagnostic tests are required.[1]S. schenckii infection may also be confused with other diseases such aspyoderma gangrenosum[20] orsarcoidosis[22] further underscoring the need for accurate diagnoses.
Growing the fungus in pure culture is the most reliable way to identifySporothrix infection.[2] A patient swab orbiopsy is used to inoculateSabouraud agar[18] orbrain heart infusion agar.[16] Sabouraud agar is incubated at room temperature for macroscopic observation of the off-white or dark brown/blackhyphal form of the fungus and microscopic examination of hyphae and conidia.[2][18] The yeast form is grown on brain heart infusion agar at 37 °C (99 °F).[16] Observation of yeast colonies in addition to the hyphal form is required to confirm diagnosis ofS. schenckii.[20] Growth on media occurs in approximately one to three weeks[16] meaning that results from patient cultures will not be immediately available to make treatment decisions.
A skin test uses anantigen generated from laboratory grownS. schenckii to challenge the patient's immune system. The antigen isintradermally injected and the test is interpreted 48 hours later. Erythema at the site of injection indicates a positive response.[1][16] The major advantage of this test is its rapidity and ease of use. Although it provides results more quickly than a fungal culture, the sporotrichin skin test has some important limitations.Cross reactions with other fungal species[23] as well as positive reactions in healthy individuals[1] have been observed. In addition, the term "sporotrichin" does not indicate a specific molecule but only any antigen derived fromS. schenckii. The specific antigen used in skin testing is not standardized with multiple studies being conducted with widely varying preparations. However, owing to its simplicity, skin testing remains the method of choice for large-scale epidemiological investigations.[1]
Molecular diagnostic techniques have been used as rapid,sensitive, and specific tests for the presence ofS. schenckii.[24]PCR methods that specifically amplify theribosomal RNA gene have been shown to detectS. schenckii in clinical samples with minimal interference from host or bacterial sequences.[25] Serumantibody reactivity toS. schenckii antigens can also be quantified byELISA.[26] Although molecular biology techniques are promising in their use as diagnostic tools, their cost as well as requirement for specialized equipment and expertise means that more traditional diagnostic methods still play an important role inSporothrix schenckii treatment.
Where available and tolerated by the patient, antifungal drugs are indicated as the primary treatment of sporotrichosis. For cutaneous infectionitraconazole orterbinafine are the primary treatment withfluconazole being recommended if primary antifungals are not well tolerated. When infection isdisseminated throughout the body,Amphotericin B is the drug of choice. To completely clear the fungus, the course of treatment generally lasts from 3 to 6 months.[13]In vitro susceptibility to antifungal drugs has been shown to be dependent on the growth phase (hyphal or yeast) of the fungus.[27]
Oral administration of a saturatedpotassium iodide solution was the first effective treatment for sporotrichosis and remains the drug of choice in many parts of the world owing to its low cost and availability.[28] Although effective, it has since been supplanted by antifungal drugs[13] due to the requirement for multiple daily doses as well side effects including gastrointestinal upset orthyroid imbalance.[28]
S. schenckii synthesizesmelanin bothin vitro andin vivo[5] Melanin production is a virulence factor found in many fungi that cause disease[29] and its production inS. schenckii protects the fungus from oxidative stress as well asultraviolet light andmacrophage killing. Melanin has been shown to be synthesized using the 1,8-DHNpentaketide pathway (below).[5]
Adhesion is an important component of pathogenesis. The yeast form ofS. schenckii shows an increased ability to bind[1] to the host extracellular matrix proteinsfibronectin andlaminin using two separate receptors specific for these proteins.[31]
S. schenckii breaks down proteins by producing two separateproteases, aserine protease and anaspartic protease.[32] These proteases appear to be essential for fungal growth. However, they have some functional overlap as the inactivation of either protein does not affect growth but inactivation of both inhibits the fungus.[33] Protease activity has been shown to be important inin vivo infection of mice.[32] Substrates for these proteases include the skin proteinstype-I collagen,stratum corneum, andelastin.[32]
Growing at host body temperature (37 °C (99 °F)) is an important requirement for pathogenesis. Some strains ofS. schenckii are restricted to growing at 35 °C (95 °F) and consequently usually cause disease only on the skin as it is cooler than the body's interior. Those that are capable of growth at body temperature are more often associated with disseminated disease.[32]
Infection byS. schenckii is generallyself-limiting in immunocompetent hosts. The immune response prevents fungal dissemination and is the reason that mostSporothrix infections arecutaneous.[34]
The yeast form ofS. schenckii is effectivelyphagocytosed bycells of the innate immune system[34] and are recognized based on the sugars displayed on their surface[35] or lipids in the yeast cell membrane.[34] Although they are taken up, they are not efficiently killed. It is hypothesized thatergosterol peroxide reacts with and detoxifiesreactive oxygen species generated by therespiratory burst used by phagocytes to kill cells they have ingested.[34]S. schenckii is also capable of modulating the immune response to promote its own survival by blockingcytokine production by macrophages.[34]
The specific immune response is active later in infection and involves bothB cells andT cells. Severe sporotrichosis is rare in endemic areas where humans are in near constant contact withS. schenckii spores. This fact, combined with the increased severity of disease in immunocompromised patients points to an important role forspecific immunity inS. schenckii infection.[34] Patients with sporotrichosis have been shown to produce antibodies specific toS. schenckii[36] and these antibodies may actually be protective against the disease.[1]