Sporothrix schenckii- An Overview

What is Sporothrix schenckii?

Sporothrix schenckii is a dimorphic fungus that is widely distributed in soil and in and on living and dead decaying environments.

• It is a pathogenic fungus that causes an infection known as sporotrichosis, in both animals and humans.
• Sporotrichosis is a chronic mycotic infection that affects the cutaneous and subcutaneous tissues.
• The fungal infection is associated with the formation of small, ulcerative, and suppurative lesions on and in the skin tissues.
• It can also affect the lymphatic system by forming nodular lesions which can be ulcerative and suppurative.
• The fungus gains entry into the host through skin abrasions and sometimes through inhalation into the lungs.
• Evidence of secondary spread to the muscles and bones is rare, with occasional infection of the central nervous system, lungs, and the genitourinary tract have been reported.
• Sporothrix schenckii was first isolated in 1896 by Benjamin Schenck, a medical student at the Johns Hopkins Hospital in Baltimore, MD, from a 36-year-old male patient presenting lesions on the right hand and arm.

Habitat of Sporothrix schenckii

• This fungus is commonly found in soil.
• It can also be found on living plants such as barberry shrubs and roses or in plant debris such as sphagnum moss and pine bark mulch.
• Sporothrix schenckii grows as a mold in the environment and at temperatures below 35°C.
• It transforms into a yeast form in vivo and at temperatures above 35°C.
• Sporotrichosis, an infection caused by Sporotrix schenckii is an occupational disease to florists, gardeners, and foresty workers.
• It is commonly prevalent in Tropical and subtropical regions.

Morphology of Sporothrix schenckii

• Sporothrix schenckii is a dimorphic fungus.
• In the basic mycological culture at 25°C, it has a filamentous form that is composed of hyaline, septate hyphae 1 to 2 μm wide.
• The fungal growth in the colonies is characterized by branched septate hyphae which produce small distinct asexual spores known as conidia of 3–5 μm, which are brown in color.
• The conidia are produced by conidiophores, which arise at right angles from the septate hyphae.
• The conidiophore, are tapered at the ends.
• The formed conidia are clustered on tiny denticles at the apex of the conidiophore forming a flower-like appearance.
• The conidia are ovoid or elongated, 3-6 x 2-3 µm, hyaline, single-celled, and smooth-walled.
• Large singly occurring conidia may also be formed as the fungal culture ages.
• The large conidia are dark, thick-walled obovate to angular.
• In rich media budding yeast cells which are fusiform of about 1–3 × 3–10 μm are formed which are spherical, or oval-shaped.

Figure: Culture of Sporothrix schenckii (Sabouraud media, 28 °C) Filamentous state with thin hyphae and denticle microconidia like “daisy flowers” (Erythrosine, 40×). Image Source: MDPI.

Cultural Characteristics of Sporothrix schenckii

• In routine mycological agar media such as malt extract agar and potato dextrose agar, at room temperature 25°C, they grow slowly, forming blackish/greyish and shiny colonies that mature to moist, glabrous, wrinkled, and fuzzy colonies, colored in black.
• In a rich medium such as brain heart infusion media (BHI) at  35-37°C, Sporotrix schenckii is thermally dimorphic whose growth is characterized by multiple budding yeast cells.
• In the BHI medium, they produce colonies that are glabrous, white-greyish to yellowish color,  yeast cells.

Transmission of Sporothrix schenckii

• The fungus inoculation into the host is via traumatic implantation of the fungus from contaminated soil, plants, and organic matter with the fungus.
• It is common in florists, gardeners, miners, and forest workers.
• Zoonotic transmission from cats has also been reported in a few cases in Brazil.
• It has a 1-12 week incubation period.

Pathogenesis of Sporothrix schenckii

Virulence Factors of Sporothrix schenckii

Thermotolerance

• Sporothrix schenckii has the ability to grow in temperatures of 35-37°C.
• At 35°C, it can cause lymphatic sporotrichosis and at 37°C, it can cause disseminated and extracutaneous lesions of sporotrichosis.

Melanin synthesis

• Sporothrix schenckii has the ability to synthesize melanin, an insoluble compound that has been linked to the virulence of many fungal groups.
• The melanin is found on the dematiaceous conidia of the fungus
• Conidial melanization enhances the resistance of Sporotrix schenckii to macrophage phagocytosis initiating the first stage of infection by the conidia spores, the infective particle of the fungus.
•  The melanin pigmentation plays a major role in causing cutaneous sporotrichosis by enhancing the invasiveness of the fungus into the host.

Figure: Structures of some intermediates in the pentaketide pathway of melanin biosynthesis in S. schenckii. Image Source: Wikipedia.

Adherence

• Sporotrix schenckii has adhesins such as integrins and adhesin lectin-like molecules that are able to recognize the glycoproteins on the extracellular matrix of the cutaneous tissues i.e fibronectin, laminin and type II collagen.
• The fibronectin adhesins are located on the surface of yeast cells and they attribute to the fungal adherence factors to the host.
• Laminin receptors are located on the fungus hyphae and yeasts which have the ability to bind to the extracellular matrix.
• The presence of these adhesins favors the fungus adherence to the host tissues and enhance disease dissemination.

Clinical Manifestations of Sporotrichosis

Lymphocutaneous infection

• It is the most common manifestation of Sporotrix schenckii
• Lesions occur on the hands and arms, lower extremities, trunk, and face.
• Primary lesions occur within the first few weeks of fungal inoculation.
• The lesions are small nodules that progress to ulceration
• The lesions are a bit painful and nonpruritic.
• New nodules spread on the lymphatics and become ulcerated.
• Lymphangitis may develop, making the lymph nodes swollen and painful.

Cutaneous Infection

• Sporothrix schenckii is a common causative agent of suppurative and granulomatous inflammatory reaction in the dermis and subcutaneous tissue.
• It is characterized by microabscess and fibrosis, hyperkeratosis, parakeratosis, and pseudoepitheliomatous hyperplasia.

Fixed Cutaneous Infection

• This is the development of a single lesion normally on the face.
• The lesion may be ulcerated or verrucous
• The lesion only disappears on antifungal therapy.

Osteoarticular sporotrichosis

• It is a rare condition of sporotrichosis, commonly affecting alcoholics
• It is characterized by septic arthritis which occurs due to traumatic inoculation which spreads to the joints.
• Bursitis and tenosynovitis can occur presented with carpal tunnel syndrome.

Pulmonary sporotrichosis

• It is a subacute to chronic infections
• It is common in persons with Chronic Obstructive Pulmonary Disease (COPD).
• It occurs after the inhalation of conidia.
• It is characterized by fever, fatigue, weight loss, coughing, sputum productions, and hemoptysis
• Infected individuals often have chronic cavitary pulmonary histoplasmosis, tuberculosis, or atypical mycobacterial infection.

Diagnosis of Sporotrichosis

Specimen: Tissue biopsy,  pus from lesions, sputum, urine, blood, and cerebrospinal and synovial fluids.

Direct Examination

• 10% potassium hydroxide (KOH) wet mount to observe for budding yeast cells
• Gram staining stains the yeast cells gran positive.

Figure: Sporothrix schenckii conidiophores and conidia at 25°C. Image Source: The University of Adelaide.

Histological Examination 

• Hematoxylin and eosin (H&E) stain,
• Gomori methenamine silver (GMS)
• Periodic acid-Schiff (PAS) stain

Figure: Sporothrix schenckii PAS stained tissue section showing budding yeast-like cells. Image Source: The University of Adelaide.

Cultural Examination

• Sabouraud agar with chloramphenicol and on media with cycloheximide, such as mycobiotic agar, growth occurs in 5-7 days at 25°C, forming filamentous hyaline colonies which become dark at the center as the culture ages. Dematiaceous conidia are also observed.
• Potato Dextrose Agar and Cornmeal agar are used to show conidiogenesis.
• Brain Heart Infusion Agar, Chocolate agar and blood agar are used to show dimorphism at 35 to 37°C. Growth of colonies develops within 5-7 days to form yeast cell colonies which are creamy and yellow, to tan color.

Figure: Sporothrix schenckii culture at 25C and budding yeast cells in BHI at 37°C. Image Source: The University of Adelaide.

Molecular Detection

• Detection of PCR amplicons
• Oligonucleotide primers for differentiation of Sporortrix schenckii from other fungal species.

Serological Test

• Tube agglutination test to detect for agglutinin antibodies (high titers)
• Latex Agglutination – Antigen-coated latex particle to detect for sporotrichin antigen in the sera of infected patients

Sporotrichin Skin Test

• This test is meant to detect delayed hypersensitivity (cellular immune response).
• It can detect and confirm the present and previous infection by Sporothrix schenckii.
• The sporotrichin skin test has been used to confirm the diagnosis of bulbar conjunctival sporotrichosis.

Figure: Recognition of Sporothrix species using classical and molecular approaches. Image Source: https://doi.org/10.1093/mmy/myx103

Treatment of Sporotrichosis

• Oral administration of a saturated solution of potassium iodide
• Itraconazole is currently the first-choice treatment
• Systemic infection can be treated with amphotericin B

Prevention and Control of Sporotrichosis

• Putting on protective clothing such as gloves and long sleeves during high-risk activities, for example, handling sphagnum moss, wires, rose bushes, hay bales, conifer (pine) seedlings, or other materials that may facilitate the exposure to the fungus
• Cats with sporotrichosis should be correctly treated and kept isolated in a proper place to prevent zoonotic transmission.

References and Sources

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