Sporothrix schenckii: Difference between revisions

Jump to navigation Jump to search
No edit summary
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{Sporotrichosis}}{{Taxobox
{{Sporotrichosis}}
{{Taxobox
| image = Conidiophores and conidia of the fungus Sporothrix schenckii PHIL 4208 lores.jpg
| image = Conidiophores and conidia of the fungus Sporothrix schenckii PHIL 4208 lores.jpg
| image_width = 220px
| image_width = 220px
Line 19: Line 20:


==Overview==
==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 [[sphagnum|peat moss]]. It can infect humans as well as animals and is the causative agent of [[sporotrichosis]], commonly known as "rose handler's disease".<ref name = "Vasquez">{{cite journal |author=Vásquez-del-Mercado E, Arenas R, Padilla-Desgarenes C |title=Sporotrichosis |journal=Clin. Dermatol. |volume=30 |issue=4 |pages=437–43 |date=July 2012 |pmid=22682194 |doi=10.1016/j.clindermatol.2011.09.017}}</ref> 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 [[immunocompetence|healthy]] individuals but is rarely life-threatening and can be treated with [[#Treatment|antifungals]]. In the environment, ''Sporothrix schenckii'' exists as a filamentous [[hypha]]e. 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]].<ref name = "Barros">{{cite journal |author=Barros MB, de Almeida Paes R, Schubach AO |title=''Sporothrix schenckii'' and Sporotrichosis |journal=Clin. Microbiol. Rev. |volume=24 |issue=4 |pages=633–54 |date=October 2011 |pmc=3194828 |doi=10.1128/cmr.00007-11 |pmid=21976602}}</ref>
'''''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 [[sphagnum|peat moss]]. It can infect humans as well as animals and is the causative agent of [[sporotrichosis]], commonly known as "rose handler's disease".<ref name="Vasquez">{{cite journal |author=Vásquez-del-Mercado E, Arenas R, Padilla-Desgarenes C |title=Sporotrichosis |journal=Clin. Dermatol. |volume=30 |issue=4 |pages=437–43 |date=July 2012 |pmid=22682194 |doi=10.1016/j.clindermatol.2011.09.017}}</ref> 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 [[immunocompetence|healthy]] individuals but is rarely life-threatening and can be treated with [[#Treatment|antifungals]]. In the environment, ''Sporothrix schenckii'' exists as a filamentous [[hypha]]e. 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]].<ref name="Barros">{{cite journal |author=Barros MB, de Almeida Paes R, Schubach AO |title=''Sporothrix schenckii'' and Sporotrichosis |journal=Clin. Microbiol. Rev. |volume=24 |issue=4 |pages=633–54 |date=October 2011 |pmc=3194828 |doi=10.1128/cmr.00007-11 |pmid=21976602}}</ref>


==Morphology==
==Morphology==
Line 26: Line 27:


===Hyphal===
===Hyphal===
When in the environment or grown in the laboratory at {{convert|25|C|F}} ''S. schenckii'' assumes its hyphal form.<ref name = Morris-Jones /> 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).<ref name = Barros /> Microscopically, hyphae are [[hypha#Structure|septate]] approximately 1 to 2μm 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.<ref name = "MycologyOnline">[http://www.mycology.adelaide.edu.au/Fungal_Descriptions/Hyphomycetes_%28dematiaceous%29/Sporothrix/] Mycology Online - University of Adelaide</ref>
When in the environment or grown in the laboratory at {{convert|25|C|F}} ''S. schenckii'' assumes its hyphal form.<ref name="Morris-Jones" /> 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).<ref name="Barros" /> Microscopically, hyphae are [[hypha#Structure|septate]] approximately 1 to 2μm 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.<ref name="MycologyOnline">[http://www.mycology.adelaide.edu.au/Fungal_Descriptions/Hyphomycetes_%28dematiaceous%29/Sporothrix/] Mycology Online - University of Adelaide</ref>


===Yeast===
===Yeast===
At {{convert|37|C|F}} either in the laboratory or in host tissue, ''S. schenckii'' assumes its yeast form. [[Macroscopic scale|Macroscopically]], the yeast form grows as smooth white or off-white colonies. Microscopically, yeast cells are 2 to 6μm long and show an elongated cigar-shaped morphology.<ref name = Barros />
At {{convert|37|C|F}} either in the laboratory or in host tissue, ''S. schenckii'' assumes its yeast form. [[Macroscopic scale|Macroscopically]], the yeast form grows as smooth white or off-white colonies. Microscopically, yeast cells are 2 to 6μm long and show an elongated cigar-shaped morphology.<ref name="Barros" />
 
==Epidemiology and Risk Factors==
''S. schenckii'' has a worldwide distribution<ref name = Barros /> but certain areas of the world including [[Peru]], have a higher incidence of disease.<ref name = "Pappas">{{cite journal |author=Pappas PG, Tellez I, Deep AE, Nolasco D, Holgado W, Bustamante B |title=Sporotrichosis in Peru: description of an area of hyperendemicity |journal=Clin. Infect. Dis. |volume=30 |issue=1 |pages=65–70 |date=January 2000 |pmid=10619735 |doi=10.1086/313607}}</ref> Based on [[sequence analysis]]<ref name = "Marimon">{{cite journal |author=Marimon R, Gené J, Cano J, Trilles L, Dos Santos Lazéra M, Guarro J |title=Molecular phylogeny of ''Sporothrix schenckii'' |journal=J. Clin. Microbiol. |volume=44 |issue=9 |pages=3251–6 |date=September 2006 |pmc=1594699 |doi=10.1128/jcm.00081-06 |pmid=16954256}}</ref> it has been found that ''S. schenckii'' isolates can be placed in [[phylogenetics|phylogenetic groups]] that reflect the region from which they were isolated. ''S. schenckii'' is often isolated from plants and associated packing material.<ref name = "Dixon">{{cite journal |author=Dixon DM, Salkin IF, Duncan RA, ''et al.'' |title=Isolation and characterization of ''Sporothrix schenckii'' from clinical and environmental sources associated with the largest U.S. epidemic of sporotrichosis |journal=J. Clin. Microbiol. |volume=29 |issue=6 |pages=1106–13 |date=June 1991 |pmc=269953 |pmid=1864926}}</ref> [[gardening|Gardeners]],<ref name = "Wisconsin">{{cite journal |author= |title=Sporotrichosis associated with Wisconsin sphagnum moss |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=31 |issue=40 |pages=542–4 |date=October 1982 |pmid=6817054}}</ref> [[landscape contracting|landscapers]],<ref name = "Seedlings">{{cite journal |author= |title=Multistate outbreak of sporotrichosis in seedling handlers, 1988 |journal=MMWR Morb. Mortal. Wkly. Rep. |volume=37 |issue=42 |pages=652–3 |date=October 1988 |pmid=2971870}}</ref> and [[forestry|foresters]]<ref name = Dixon /> 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.<ref name = "Cats">{{cite journal |author=Barros MB, Schubach Ade O, do Valle AC, ''et al.'' |title=Cat-transmitted sporotrichosis epidemic in Rio de Janeiro, Brazil: description of a series of cases |journal=Clin. Infect. Dis. |volume=38 |issue=4 |pages=529–35 |date=February 2004 |pmid=14765346 |doi=10.1086/381200}}</ref> [[Immunodeficiency|Immunocompromised]] individuals are at increased risk of infection and such patients often exhibit more severe forms of disease.<ref name = Kauffman /><ref name = "al-Tawfiq">{{cite journal |author=al-Tawfiq JA, Wools KK |title=Disseminated sporotrichosis and ''Sporothrix schenckii'' fungemia as the initial presentation of human immunodeficiency virus infection |journal=Clin. Infect. Dis. |volume=26 |issue=6 |pages=1403–6 |date=June 1998 |pmid=9636870 |doi=10.1086/516356}}</ref><ref name = "Galhardo">{{cite journal |author=Galhardo MC, Silva MT, Lima MA, ''et al.'' |title=''Sporothrix schenckii'' meningitis in AIDS during immune reconstitution syndrome |journal=J. Neurol. Neurosurg. Psychiatr. |volume=81 |issue=6 |pages=696–9 |date=June 2010 |pmid=20392979 |doi=10.1136/jnnp.2009.173187}}</ref>
 
==Sporotrichosis==
[[File:Feline sporotrichosis 3.jpg|thumb|100px|Cutaneous sporotrichosis of a cat's paw showing ulcerations.]]
''S. schenckii'' most commonly enters the body through minor trauma that compromises the [[epidermis (skin)#Function|skin barrier]].<ref name = Kauffman /> It is this route of infection, coupled with its presence on [[rose]]s that give sporotrichosis its common name of "rose-handler's disease"<ref name = IowaState /> or "rose thorn disease".<ref name = "RoseSociety">[http://www.ars.org/pdfs/thorn_disease.pdf] American Rose Society</ref> Inhalation of spores is a rare route of infection largely associated with immunocompromised hosts.<ref name = Medscape />
 
===Cutaneous and Lymphocutaneous===
The [[cutaneous condition|cutaneous]] form of disease is caused by introduction of ''S. schenckii'' into the body through disruption of the skin barrier.<ref name = Kauffman /> The first symptom of cutaneous sporotrichosis is a small skin [[lesion]]. These lesions may show [[ulcer (dermatology)|ulceration]] and/or [[erythema]].<ref name = Barros /> Commonly, infection spreads through the [[lymph]] along [[lymphatic vessel]]s and causes lymphocutaneous sporotrichosis. This form of disease is characterized by the appearance of lesions at sites distant to the initial infection.<ref name = Barros /> Infection can occur in nonhuman animals and may be transmitted to humans through contact. [[Veterinary physician|Veterinarians]] are at particularly high risk of contracting disease from animals ([[zoonosis|zoonotic infection]]).<ref name = "AVMA">[https://www.avma.org/News/Journals/Collections/Documents/javma_223_8_1123.pdf] American Veterinary Medical Association</ref>
 
===Disseminated===
[[Disseminated disease]] occurs when the fungus spreads throughout the body. Found only in immunocompromised patients,<ref name = Barros/><ref name = al-Tawfiq /><ref name = Medscape /> it is a very severe condition. When infection becomes disseminated, ''S. schencki'' can afflict joints, the brain, and the spine.<ref name = Barros /> Patients with this condition must be treated aggressively with [[antifungal medication|antifungals]] and may remain on [[antimicrobial prophylaxis|prophylactic]] antifungal drugs for life to prevent recurrence or reinfection.<ref name = Kauffman />
 
==Diagnostic Tests==
''Sporothrix'' infection presents macroscopically with nonspecific [[#Sporotrichosis|symptoms]].<ref name = "DrFungus">[http://www.doctorfungus.org/Thefungi/sporothrix.php ''Sporothrix'' spp.] Doctor Fungus</ref> In the clinical laboratory, many fungi isolated in culture are disregarded as [[contamination|contaminants]].<ref name = "Ban-Ami">{{cite journal |author=Ben-Ami R, Lewis RE, Raad II, Kontoyiannis DP |title=Phaeohyphomycosis in a tertiary care cancer center |journal=Clin. Infect. Dis. |volume=48 |issue=8 |pages=1033–41 |date=April 2009 |pmid=19267655 |doi=10.1086/597400}}</ref> Therefore, accurate patient histories are important<ref name = Vasquez /> to establish suspicion of sporotrichosis and to inform which diagnostic tests are required.<ref name = Barros /> ''S. schenckii'' infection may also be confused with other diseases such as [[pyoderma gangrenosum]]<ref name = DrFungus /> or [[sarcoidosis]]<ref name = "Singh">{{cite journal |author=Singh MF, Fernandes SR, Samara AM |title=''Sporothrix schenckii'' infection mimicking sarcoidosis |journal=Rheumatology (Oxford) |volume=43 |issue=2 |pages=248–9 |date=February 2004 |pmid=14739470 |doi=10.1093/rheumatology/keh010}}</ref> further underscoring the need for accurate diagnoses.
 
===Primary Cultures===
Growing the fungus in pure culture is the most reliable way to identify ''Sporothrix'' infection.<ref name = Vasquez /> A patient swab or [[biopsy]] is used to inoculate [[Sabouraud agar]]<ref name = "Medscape">[http://emedicine.medscape.com/article/1091159-workup] Medscape</ref> or [[brain heart infusion broth|brain heart infusion agar]].<ref name = "IowaState">[http://www.cfsph.iastate.edu/Factsheets/pdfs/sporotrichosis.pdf]</ref> Sabouraud agar is incubated at room temperature for macroscopic observation of the off-white or dark brown/black [[hypha]]l form of the fungus and microscopic examination of hyphae and conidia.<ref name = Vasquez /><ref name = Medscape /> The yeast form is grown on brain heart infusion agar at {{convert|37|°C|°F}}.<ref name = IowaState /> Observation of yeast colonies in addition to the hyphal form is required to confirm diagnosis of ''S. schenckii''.<ref name = DrFungus /> Growth on media occurs in approximately one to three weeks<ref name = IowaState /> meaning that results from patient cultures will not be immediately available to make treatment decisions.
 
===Sporotrichin Skin Test===
A skin test uses an [[antigen]] generated from laboratory grown ''S. schenckii'' to challenge the patient's immune system. The antigen is [[dermis|intradermally injected]] and the test is interpreted 48 hours later. Erythema at the site of injection indicates a positive response.<ref name = "Barros" /><ref name = IowaState /> 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-reactivity|Cross reactions]] with other fungal species<ref name = "Ishizaki">{{cite journal |author=Ishizaki H, Nakamura Y, Kariya H, Iwatsu T, Wheat R |title=Delayed hypersensitivity cross-reactions between ''Sporothrix schenckii'' and ''Ceratocystis'' species in sporotrichotic patients |journal=J. Clin. Microbiol. |volume=3 |issue=6 |pages=545–7 |date=June 1976 |pmc=274353 |pmid=59734}}</ref> as well as positive reactions in healthy individuals<ref name = Barros /> have been observed. In addition, the term "sporotrichin" does not indicate a specific molecule but only any antigen derived from ''S. 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.<ref name = Barros />
 
===Molecular Methods===
[[Molecular pathology|Molecular diagnostic]] techniques have been used as rapid, [[sensitivity and specificity|sensitive, and specific]] tests for the presence of ''S. schenckii''.<ref>[http://jay.up.poznan.pl/JAG/pdfy/2004_Volume_45/2004_Volume_45_1-3-15.pdf] Fungal Molecular Diagnostics</ref> [[polymerase chain reaction|PCR]] methods that specifically amplify the [[18S ribosomal RNA|ribosomal RNA]] gene have been shown to detect ''S. schenckii'' in clinical samples with minimal interference from host or bacterial sequences.<ref name = "Hu">{{cite journal |author=Hu S, Chung WH, Hung SI, ''et al.'' |title=Detection of ''Sporothrix schenckii'' in clinical samples by a nested PCR assay |journal=J. Clin. Microbiol. |volume=41 |issue=4 |pages=1414–8 |date=April 2003 |pmc=153868 |doi=10.1128/jcm.41.4.1414-1418.2003 |pmid=12682123}}</ref> Serum [[antibody]] reactivity to ''S. schenckii'' antigens can also be quantified by [[ELISA]].<ref name = "Paes">{{cite journal |author=Almeida-Paes R, Pimenta MA, Pizzini CV, ''et al.'' |title=Use of mycelial-phase ''Sporothrix schenckii'' exoantigens in an enzyme-linked immunosorbent assay for diagnosis of sporotrichosis by antibody detection |journal=Clin. Vaccine Immunol. |volume=14 |issue=3 |pages=244–9 |date=March 2007 |pmc=1828849 |doi=10.1128/cvi.00430-06 |pmid=17215334}}</ref> 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 in ''Sporothrix schenckii'' treatment.
 
==Treatment==
 
===Antifungal Drugs===
Where available and tolerated by the patient, antifungal drugs are indicated as the primary treatment of sporotrichosis. For cutaneous infection [[itraconazole]] or [[terbinafine]] are the primary treatment with [[fluconazole]] being recommended if primary antifungals are not well-tolerated. When infection is [[#Disseminated|disseminated]] 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.<ref name = "Kauffman">{{cite journal |author=Kauffman CA, Bustamante B, Chapman SW, Pappas PG |title=Clinical practice guidelines for the management of sporotrichosis: 2007 update by the Infectious Diseases Society of America |journal=Clin. Infect. Dis. |volume=45 |issue=10 |pages=1255–65 |date=November 2007 |pmid=17968818 |doi=10.1086/522765}}</ref> ''[[In vitro]]'' susceptibility to antifungal drugs has been shown to be dependent on the growth phase (hyphal or yeast) of the fungus.<ref>{{cite journal |author=Trilles L, Fernández-Torres B, Dos Santos Lazéra M, ''et al.'' |title=In vitro antifungal susceptibilities of ''Sporothrix schenckii'' in two growth phases |journal=Antimicrob. Agents Chemother. |volume=49 |issue=9 |pages=3952–4 |date=September 2005 |pmc=1195444 |doi=10.1128/aac.49.9.3952-3954.2005 |pmid=16127080}}</ref>
 
===Potassium Iodide===
Oral administration of a saturated [[potassium 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.<ref name = "Sterling">{{cite journal |author=Sterling JB, Heymann WR |title=Potassium iodide in dermatology: a 19th century drug for the 21st century-uses, pharmacology, adverse effects, and contraindications |journal=J. Am. Acad. Dermatol. |volume=43 |issue=4 |pages=691–7 |date=October 2000 |pmid=11004629 |doi=10.1067/mjd.2000.107247}}</ref> Although effective, it has since been supplanted by antifungal drugs<ref name = Kauffman /> due to the requirement for multiple daily doses as well side effects including gastrointestinal upset or [[hyperthyroidism|thyroid imbalance]].<ref name = Sterling />


==Virulence Factors==
==Virulence Factors==


===Melanin Production===
===Melanin Production===
''S. schenckii'' synthesizes [[melanin]] both ''in vitro'' and ''[[in vivo]]''<ref name = "Morris-Jones">{{cite journal |author=Morris-Jones R, Youngchim S, Gomez BL, ''et al.'' |title=Synthesis of melanin-like pigments by ''Sporothrix schenckii'' in vitro and during mammalian infection |journal=Infect. Immun. |volume=71 |issue=7 |pages=4026–33 |date=July 2003 |pmc=161969 |doi=10.1128/iai.71.7.4026-4033.2003 |pmid=12819091}}</ref>  
''S. schenckii'' synthesizes [[melanin]] both ''in vitro'' and ''[[in vivo]]''<ref name="Morris-Jones">{{cite journal |author=Morris-Jones R, Youngchim S, Gomez BL, ''et al.'' |title=Synthesis of melanin-like pigments by ''Sporothrix schenckii'' in vitro and during mammalian infection |journal=Infect. Immun. |volume=71 |issue=7 |pages=4026–33 |date=July 2003 |pmc=161969 |doi=10.1128/iai.71.7.4026-4033.2003 |pmid=12819091}}</ref>  
Melanin production is a virulence factor found in many fungi that cause disease<ref name = "Revankar">{{cite journal |author=Revankar SG, Sutton DA |title=Melanized fungi in human disease |journal=Clin. Microbiol. Rev. |volume=23 |issue=4 |pages=884–928 |date=October 2010 |pmc=2952981 |doi=10.1128/cmr.00019-10 |pmid=20930077}}</ref> 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 (below).<ref name = Morris-Jones />
Melanin production is a virulence factor found in many fungi that cause disease<ref name="Revankar">{{cite journal |author=Revankar SG, Sutton DA |title=Melanized fungi in human disease |journal=Clin. Microbiol. Rev. |volume=23 |issue=4 |pages=884–928 |date=October 2010 |pmc=2952981 |doi=10.1128/cmr.00019-10 |pmid=20930077}}</ref> 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 (below).<ref name="Morris-Jones" />


===Adhesins===
===Adhesins===
Adhesion is an important component of pathogenesis. The yeast form of ''S. schenckii'' shows an increased ability to bind<ref name = "Barros" /> to the host extracellular matrix proteins [[fibronectin]] and [[laminin]] using two separate receptors specific for these proteins.<ref name = "Lima">{{cite journal |author=Lima OC, Bouchara JP, Renier G, Marot-Leblond A, Chabasse D, Lopes-Bezerra LM |title=Immunofluorescence and flow cytometry analysis of fibronectin and laminin binding to ''Sporothrix schenckii'' yeast cells and conidia |journal=Microb. Pathog. |volume=37 |issue=3 |pages=131–40 |date=September 2004 |pmid=15351036 |doi=10.1016/j.micpath.2004.06.005}}</ref>
Adhesion is an important component of pathogenesis. The yeast form of ''S. schenckii'' shows an increased ability to bind<ref name="Barros" /> to the host extracellular matrix proteins [[fibronectin]] and [[laminin]] using two separate receptors specific for these proteins.<ref name="Lima">{{cite journal |author=Lima OC, Bouchara JP, Renier G, Marot-Leblond A, Chabasse D, Lopes-Bezerra LM |title=Immunofluorescence and flow cytometry analysis of fibronectin and laminin binding to ''Sporothrix schenckii'' yeast cells and conidia |journal=Microb. Pathog. |volume=37 |issue=3 |pages=131–40 |date=September 2004 |pmid=15351036 |doi=10.1016/j.micpath.2004.06.005}}</ref>


===Proteases===
===Proteases===
''S. schenckii'' breaks down proteins by producing two separate [[protease]]s, a [[serine protease]] and an [[aspartate protease|aspartic protease]].<ref name = "Hogan">{{cite journal |author=Hogan LH, Klein BS, Levitz SM |title=Virulence factors of medically important fungi |journal=Clin. Microbiol. Rev. |volume=9 |issue=4 |pages=469–88 |date=October 1996 |pmc=172905 |pmid=8894347}}</ref> 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.<ref name = "Tsuboi">{{cite journal |author=Tsuboi R, Sanada T, Ogawa H |title=Influence of culture medium pH and proteinase inhibitors on extracellular proteinase activity and cell growth of ''Sporothrix schenckii'' |journal=J. Clin. Microbiol. |volume=26 |issue=7 |pages=1431–3 |date=July 1988 |pmc=266631 |pmid=3045155}}</ref> Protease activity has been shown to be important in ''in vivo'' infection of mice.<ref name = "Hogan" /> Substrates for these proteases include the skin proteins [[type-I collagen]], [[stratum corneum]], and [[elastin]].<ref name = "Hogan" />
''S. schenckii'' breaks down proteins by producing two separate [[protease]]s, a [[serine protease]] and an [[aspartate protease|aspartic protease]].<ref name="Hogan">{{cite journal |author=Hogan LH, Klein BS, Levitz SM |title=Virulence factors of medically important fungi |journal=Clin. Microbiol. Rev. |volume=9 |issue=4 |pages=469–88 |date=October 1996 |pmc=172905 |pmid=8894347}}</ref> 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.<ref name="Tsuboi">{{cite journal |author=Tsuboi R, Sanada T, Ogawa H |title=Influence of culture medium pH and proteinase inhibitors on extracellular proteinase activity and cell growth of ''Sporothrix schenckii'' |journal=J. Clin. Microbiol. |volume=26 |issue=7 |pages=1431–3 |date=July 1988 |pmc=266631 |pmid=3045155}}</ref> Protease activity has been shown to be important in ''in vivo'' infection of mice.<ref name="Hogan" /> Substrates for these proteases include the skin proteins [[type-I collagen]], [[stratum corneum]], and [[elastin]].<ref name="Hogan" />


===Heat Tolerance===
===Heat Tolerance===
Growing at host body temperature ({{convert|37|C|F}}) is an important requirement for pathogenesis. Some strains of ''S. schenckii'' are restricted to growing at {{convert|35|C|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.<ref name = "Hogan" />
Growing at host body temperature ({{convert|37|C|F}}) is an important requirement for pathogenesis. Some strains of ''S. schenckii'' are restricted to growing at {{convert|35|C|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.<ref name="Hogan" />


==Immune Response==
==Immune Response==
Infection by ''S. schenckii'' is generally [[self-limiting (biology)|self-limiting]] in immunocompetent hosts. The immune response prevents fungal dissemination and is the reason that most ''Sporothrix'' infections are [[#Cutaneous and Lymphocutaneous|cutaneous]].<ref name = "Carlos">{{cite journal |author=Carlos IZ, Sassá MF, da Graça Sgarbi DB, Placeres MC, Maia DC |title=Current research on the immune response to experimental sporotrichosis |journal=Mycopathologia |volume=168 |issue=1 |pages=1–10 |date=July 2009 |pmid=19241140 |doi=10.1007/s11046-009-9190-z}}</ref>
Infection by ''S. schenckii'' is generally [[self-limiting (biology)|self-limiting]] in immunocompetent hosts. The immune response prevents fungal dissemination and is the reason that most ''Sporothrix'' infections are [[#Cutaneous and Lymphocutaneous|cutaneous]].<ref name="Carlos">{{cite journal |author=Carlos IZ, Sassá MF, da Graça Sgarbi DB, Placeres MC, Maia DC |title=Current research on the immune response to experimental sporotrichosis |journal=Mycopathologia |volume=168 |issue=1 |pages=1–10 |date=July 2009 |pmid=19241140 |doi=10.1007/s11046-009-9190-z}}</ref>


===Innate===
===Innate===
The yeast form of ''S. schenckii'' is effectively [[phagocytosis|phagocytosed]] by [[innate immune system#Cells of the innate immune response|cells of the innate immune system]]<ref name = "Carlos" /> and are recognized based on the sugars displayed on their surface<ref name = "Oda">{{cite journal |author=Oda LM, Kubelka CF, Alviano CS, Travassos LR |title=Ingestion of yeast forms of ''Sporothrix schenckii'' by mouse peritoneal macrophages |journal=Infect. Immun. |volume=39 |issue=2 |pages=497–504 |date=February 1983 |pmc=347978 |pmid=6832808}}</ref> or lipids in the yeast cell mebrane.<ref name = "Carlos" /> 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.<ref name = "Carlos" /> ''S. schenckii'' is also capable of modulating the immune response to promote its own survival by blocking [[cytokine]] production by macrophages.<ref name = "Carlos" />
The yeast form of ''S. schenckii'' is effectively [[phagocytosis|phagocytosed]] by [[innate immune system#Cells of the innate immune response|cells of the innate immune system]]<ref name="Carlos" /> and are recognized based on the sugars displayed on their surface<ref name="Oda">{{cite journal |author=Oda LM, Kubelka CF, Alviano CS, Travassos LR |title=Ingestion of yeast forms of ''Sporothrix schenckii'' by mouse peritoneal macrophages |journal=Infect. Immun. |volume=39 |issue=2 |pages=497–504 |date=February 1983 |pmc=347978 |pmid=6832808}}</ref> or lipids in the yeast cell mebrane.<ref name="Carlos" /> 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.<ref name="Carlos" /> ''S. schenckii'' is also capable of modulating the immune response to promote its own survival by blocking [[cytokine]] production by macrophages.<ref name="Carlos" />


===Specific===
===Specific===
The specific immune response is active later in infection and involves both [[B cell]]s and [[T cell]]s. 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 points to an important role for [[adaptive immune system|specific immunity]] in ''S. schenckii'' infection.<ref name = "Carlos" /> Patients with sporotrichosis have been shown to produce antibodies specific to ''S. schenckii''<ref name = "Scott">{{cite journal |author=Scott EN, Muchmore HG |title=Immunoblot analysis of antibody responses to ''Sporothrix schenckii'' |journal=J. Clin. Microbiol. |volume=27 |issue=2 |pages=300–4 |date=February 1989 |pmc=267296 |pmid=2915023}}</ref> and these antibodies may actually be protective against the disease.<ref name = Barros />
The specific immune response is active later in infection and involves both [[B cell]]s and [[T cell]]s. 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 points to an important role for [[adaptive immune system|specific immunity]] in ''S. schenckii'' infection.<ref name="Carlos" /> Patients with sporotrichosis have been shown to produce antibodies specific to ''S. schenckii''<ref name="Scott">{{cite journal |author=Scott EN, Muchmore HG |title=Immunoblot analysis of antibody responses to ''Sporothrix schenckii'' |journal=J. Clin. Microbiol. |volume=27 |issue=2 |pages=300–4 |date=February 1989 |pmc=267296 |pmid=2915023}}</ref> and these antibodies may actually be protective against the disease.<ref name="Barros" />


==References==
==References==
Line 94: Line 62:
*[http://botit.botany.wisc.edu/toms_fungi/feb2003.html Fungus Page: ''Sporothrix schenckii'', cause of Rose-picker's Disease]
*[http://botit.botany.wisc.edu/toms_fungi/feb2003.html Fungus Page: ''Sporothrix schenckii'', cause of Rose-picker's Disease]
*[http://emedicine.medscape.com/article/228723-overview EMedicine: Sporotrichosis]
*[http://emedicine.medscape.com/article/228723-overview EMedicine: Sporotrichosis]
*[http://www.mycology.adelaide.edu.au/Fungal_Descriptions/Hyphomycetes_%28dematiaceous%29/Sporothrix/ Adelaide University: ''Sporothrix schenckii'']
*[http://www.mycology.adelaide.edu.au/Fungal_Descriptions/Hyphomycetes_%28dematiaceous%29/Sporothrix/ Adelaide University: ''Sporothrix schenckii'']
*[http://cmr.asm.org/content/24/4/633.abstract American Society for Microbiology: ''Sporothrix schenckii'' and Sporotrichosis]
*[http://cmr.asm.org/content/24/4/633.abstract American Society for Microbiology: ''Sporothrix schenckii'' and Sporotrichosis]
*[http://microbewiki.kenyon.edu/index.php/Sporothrix_schenckii Microbe wiki: ''Sporothrix schenckii'']
*[http://microbewiki.kenyon.edu/index.php/Sporothrix_schenckii Microbe wiki: ''Sporothrix schenckii'']

Revision as of 16:25, 13 January 2016

Sporotrichosis Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Sporotrichosis from other Diseases

Epidemiology and Demographics

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Chest X Ray

Treatment

Medical Therapy

Surgery

Prevention

Case Studies

Case #1

Sporothrix schenckii On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Sporothrix schenckii

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Sporothrix schenckii

CDC on Sporothrix schenckii

Sporothrix schenckii in the news

Blogs on Sporothrix schenckii

Directions to Hospitals Treating Sporotrichosis

Risk calculators and risk factors for Sporothrix schenckii

style="background:#Template:Taxobox colour;"|Template:Taxobox name
Conidiophores and conidia
Conidiophores and conidia
style="background:#Template:Taxobox colour;" | Scientific classification
Kingdom: Fungi
Division: Ascomycota
Class: Sordariomycetes
Order: Ophiostomatales
Family: Ophiostomataceae
Genus: Sporothrix
Species: S. schenckii
Binomial name
Sporothrix schenckii
Hektoen & C.F.Perkins (1900)
This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Sporotrichosis.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] Alison Leibowitz [3]

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".[1] 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.[2]

Morphology

Template:Triple image Sporothrix schenckii can be found in one of two morphologies, 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.

Hyphal

When in the environment or grown in the laboratory at 25 °C (77 °F) S. schenckii assumes its hyphal form.[3] 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).[2] Microscopically, hyphae are septate approximately 1 to 2μm 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.[4]

Yeast

At 37 °C (98.6 °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 6μm long and show an elongated cigar-shaped morphology.[2]

Virulence Factors

Melanin Production

S. schenckii synthesizes melanin both in vitro and in vivo[3] Melanin production is a virulence factor found in many fungi that cause disease[5] 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 (below).[3]

Adhesins

Adhesion is an important component of pathogenesis. The yeast form of S. schenckii shows an increased ability to bind[2] to the host extracellular matrix proteins fibronectin and laminin using two separate receptors specific for these proteins.[6]

Proteases

S. schenckii breaks down proteins by producing two separate proteases, a serine protease and an aspartic protease.[7] 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.[8] Protease activity has been shown to be important in in vivo infection of mice.[7] Substrates for these proteases include the skin proteins type-I collagen, stratum corneum, and elastin.[7]

Heat Tolerance

Growing at host body temperature (37 °C (98.6 °F)) is an important requirement for pathogenesis. Some strains of S. 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.[7]

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.[9]

Innate

The yeast form of S. schenckii is effectively phagocytosed by cells of the innate immune system[9] and are recognized based on the sugars displayed on their surface[10] or lipids in the yeast cell mebrane.[9] 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.[9] S. schenckii is also capable of modulating the immune response to promote its own survival by blocking cytokine production by macrophages.[9]

Specific

The specific immune response is active later in 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 points to an important role for specific immunity in S. schenckii infection.[9] Patients with sporotrichosis have been shown to produce antibodies specific to S. schenckii[11] and these antibodies may actually be protective against the disease.[2]

References

  1. Vásquez-del-Mercado E, Arenas R, Padilla-Desgarenes C (July 2012). "Sporotrichosis". Clin. Dermatol. 30 (4): 437–43. doi:10.1016/j.clindermatol.2011.09.017. PMID 22682194.
  2. 2.0 2.1 2.2 2.3 2.4 Barros MB, de Almeida Paes R, Schubach AO (October 2011). "Sporothrix schenckii and Sporotrichosis". Clin. Microbiol. Rev. 24 (4): 633–54. doi:10.1128/cmr.00007-11. PMC 3194828. PMID 21976602.
  3. 3.0 3.1 3.2 Morris-Jones R, Youngchim S, Gomez BL; et al. (July 2003). "Synthesis of melanin-like pigments by Sporothrix schenckii in vitro and during mammalian infection". Infect. Immun. 71 (7): 4026–33. doi:10.1128/iai.71.7.4026-4033.2003. PMC 161969. PMID 12819091.
  4. [1] Mycology Online - University of Adelaide
  5. Revankar SG, Sutton DA (October 2010). "Melanized fungi in human disease". Clin. Microbiol. Rev. 23 (4): 884–928. doi:10.1128/cmr.00019-10. PMC 2952981. PMID 20930077.
  6. Lima OC, Bouchara JP, Renier G, Marot-Leblond A, Chabasse D, Lopes-Bezerra LM (September 2004). "Immunofluorescence and flow cytometry analysis of fibronectin and laminin binding to Sporothrix schenckii yeast cells and conidia". Microb. Pathog. 37 (3): 131–40. doi:10.1016/j.micpath.2004.06.005. PMID 15351036.
  7. 7.0 7.1 7.2 7.3 Hogan LH, Klein BS, Levitz SM (October 1996). "Virulence factors of medically important fungi". Clin. Microbiol. Rev. 9 (4): 469–88. PMC 172905. PMID 8894347.
  8. Tsuboi R, Sanada T, Ogawa H (July 1988). "Influence of culture medium pH and proteinase inhibitors on extracellular proteinase activity and cell growth of Sporothrix schenckii". J. Clin. Microbiol. 26 (7): 1431–3. PMC 266631. PMID 3045155.
  9. 9.0 9.1 9.2 9.3 9.4 9.5 Carlos IZ, Sassá MF, da Graça Sgarbi DB, Placeres MC, Maia DC (July 2009). "Current research on the immune response to experimental sporotrichosis". Mycopathologia. 168 (1): 1–10. doi:10.1007/s11046-009-9190-z. PMID 19241140.
  10. Oda LM, Kubelka CF, Alviano CS, Travassos LR (February 1983). "Ingestion of yeast forms of Sporothrix schenckii by mouse peritoneal macrophages". Infect. Immun. 39 (2): 497–504. PMC 347978. PMID 6832808.
  11. Scott EN, Muchmore HG (February 1989). "Immunoblot analysis of antibody responses to Sporothrix schenckii". J. Clin. Microbiol. 27 (2): 300–4. PMC 267296. PMID 2915023.

Further reading

Template:Mycoses