Fonsecaea Pedrosoi
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''Fonsecaea pedrosoi'' is a fungal species in the family
Herpotrichiellaceae Herpotrichiellaceae is a family of ascomycetous fungi within the order Chaetothyriales and within the class Eurotiomycetes. It contains 16 genera and about 270 species. The type genus of the family, ''Herpotrichiella'', is now synonymous with '' ...
, and the major causative agent of
chromoblastomycosis Chromoblastomycosis is a long-term fungal infection of the skin and subcutaneous tissue (a chronic subcutaneous mycosis). It can be caused by many different types of fungi which become implanted under the skin, often by thorns or splinters. C ...
. This species is commonly found in tropical and sub-tropical regions, especially in South America, where it grows as a soil
saprotroph Saprotrophic nutrition or lysotrophic nutrition is a process of chemoheterotrophic extracellular digestion involved in the processing of decayed (dead or waste) organic matter. It occurs in saprotrophs, and is most often associated with fungi (f ...
. Farming activities in the
endemic Endemism is the state of a species being found in a single defined geographic location, such as an island, state, nation, country or other defined zone; organisms that are indigenous to a place are not endemic to it if they are also found elsew ...
zone are a
risk factor In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often use ...
for the development of chromoblastomycosis.


Taxonomy

''
Fonsecaea ''Fonsecaea'' is a genus of fungi in the family Herpotrichiellaceae. The type species, '' Fonsecaea pedrosoi'', is associated with the disease chromoblastomycosis Chromoblastomycosis is a long-term fungal infection of the skin and subcutaneous ...
'' is a genus of
ascomycetous Ascomycota is a phylum of the kingdom Fungi that, together with the Basidiomycota, forms the subkingdom Dikarya. Its members are commonly known as the sac fungi or ascomycetes. It is the largest phylum of Fungi, with over 64,000 species. The de ...
fungi affiliated with the family
Herpotrichiellaceae Herpotrichiellaceae is a family of ascomycetous fungi within the order Chaetothyriales and within the class Eurotiomycetes. It contains 16 genera and about 270 species. The type genus of the family, ''Herpotrichiella'', is now synonymous with '' ...
. The genus comprises three sibling species, all with pathogenic potential: ''F. pedrosoi'', '' F. monophora'' and '' F. nubica''. The species was first formally described in 1922 as ''Hormodendrum pedrosoi'' by French parasitologist
Émile Brumpt Alexandre Joseph Émile Brumpt (10 March 1877, in Paris – 8 July 1951) was a French parasitologist. He studied zoology and parasitology in Paris, obtaining his degree in science in 1901, and his medical doctorate in 1906. In 1919 he succeeded ...
. Pablo Negroni transferred it to the genus ''
Fonsecaea ''Fonsecaea'' is a genus of fungi in the family Herpotrichiellaceae. The type species, '' Fonsecaea pedrosoi'', is associated with the disease chromoblastomycosis Chromoblastomycosis is a long-term fungal infection of the skin and subcutaneous ...
'' in 1936. Sparingly branched, brownish
conidiophore A conidium ( ; ), sometimes termed an asexual chlamydospore or chlamydoconidium (), is an Asexual reproduction, asexual, non-motility, motile spore of a fungus. The word ''conidium'' comes from the Ancient Greek word for dust, ('). They are al ...
s produce clusters of 1–celled, club-shaped conidia in short, dry, unbranched chains. A
Phialophora ''Phialophora'' is a form genus of fungus with short conidiophores, sometimes reduced to phialides; their conidia are unicellular. They may be parasites (including on humans), or saprophytic (including on apples). Genetic analysis of ''Phialop ...
-like asexual state sometimes appears along with yeast cells at low pH.


Ecology and distribution

''Fonsecaea pedrosoi'' occurs in soil and on plants and trees where it grows as a
saprotroph Saprotrophic nutrition or lysotrophic nutrition is a process of chemoheterotrophic extracellular digestion involved in the processing of decayed (dead or waste) organic matter. It occurs in saprotrophs, and is most often associated with fungi (f ...
. It is found predominantly in tropical regions especially South- and Central America. All three recognized species of ''Fonsecaea'' exhibit geographically patterned genetic variation. The closely related species ''F. monophora'' and ''F. nubica'' are distributed worldwide and show the greater population-level
genetic diversity Genetic diversity is the total number of genetic characteristics in the genetic makeup of a species, it ranges widely from the number of species to differences within species and can be attributed to the span of survival for a species. It is dis ...
than the geographically restricted ''F. pedrosoi''. Environmental surveys have documented the recovery of ''F. pedrosoi'' on rotting wood of the Cambara tree, (''
Gochnatia polymorpha ''Gochnatia polymorpha'', the candeia or cambará, is a South American tree species in the family Asteraceae, native to Brazil, Bolivia, and Paraguay Paraguay (; ), officially the Republic of Paraguay ( es, República del Paraguay, links=n ...
'') from the Brazilian Corporation of Agricultural Research forest in
Colombo, Paraná Colombo is a city of about 247,000 inhabitants in the Southern Brazilian state of Paraná; is the third largest city in Greater Curitiba. It was founded on 5 February 1890. It is located at 25º17'30" S, 49º13'27" W, at an elevation of abou ...
,
Brazil Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...
. It has also been isolated from living trees, stumps, woodpiles and fence posts in central
Nigeria Nigeria ( ), , ig, Naìjíríyà, yo, Nàìjíríà, pcm, Naijá , ff, Naajeeriya, kcg, Naijeriya officially the Federal Republic of Nigeria, is a country in West Africa. It is situated between the Sahel to the north and the Gulf o ...
.


Physiology

Clinical isolates of grow consistently at temperatures up to . In contrast, environmental isolates of ''F. pedrosoi'' exhibit growth consistently up to 35 °C, and irregularly up to Physiological studies have shown the degradation of
urea Urea, also known as carbamide, is an organic compound with chemical formula . This amide has two amino groups (–) joined by a carbonyl functional group (–C(=O)–). It is thus the simplest amide of carbamic acid. Urea serves an important r ...
and
tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Gr ...
, and the lack of growth on the proteins
gelatin Gelatin or gelatine (from la, gelatus meaning "stiff" or "frozen") is a translucent, colorless, flavorless food ingredient, commonly derived from collagen taken from animal body parts. It is brittle when dry and rubbery when moist. It may also ...
,
casein Casein ( , from Latin ''caseus'' "cheese") is a family of related phosphoproteins (CSN1S1, αS1, aS2, CSN2, β, K-casein, κ) that are commonly found in mammalian milk, comprising about 80% of the proteins in cow's milk and between 20% and 60% of ...
and the
purine Purine is a heterocyclic compound, heterocyclic aromatic organic compound that consists of two rings (pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which includ ...
s
xanthine Xanthine ( or ; archaically xanthic acid; systematic name 3,7-dihydropurine-2,6-dione) is a purine base (genetics), base found in most human body tissues and fluids, as well as in other organisms. Several stimulants are derived from xanthine, incl ...
and
hypoxanthine Hypoxanthine is a naturally occurring purine derivative. It is occasionally found as a constituent of nucleic acids, where it is present in the anticodon of tRNA in the form of its nucleoside inosine. It has a tautomer known as 6-hydroxypurine. Hyp ...
. Likewise,
lipase Lipase ( ) is a family of enzymes that catalyzes the hydrolysis of fats. Some lipases display broad substrate scope including esters of cholesterol, phospholipids, and of lipid-soluble vitamins and sphingomyelinases; however, these are usually tr ...
activity was demonstrated, but
phospholipase A phospholipase is an enzyme that hydrolyzes phospholipids into fatty acids and other lipophilic substances. Acids trigger the release of bound calcium from cellular stores and the consequent increase in free cytosolic Ca2+, an essential step in ...
,
collagenase Collagenases are enzymes that break the peptide bonds in collagen. They assist in destroying extracellular structures in the pathogenesis of bacteria such as ''Clostridium''. They are considered a virulence factor, facilitating the spread of ga ...
and
amylase An amylase () is an enzyme that catalyses the hydrolysis of starch (Latin ') into sugars. Amylase is present in the saliva of humans and some other mammals, where it begins the chemical process of digestion. Foods that contain large amounts of ...
were not expressed.


Human disease

''Fonsecaea pedrosoi'' is one of several main causative agents of human
chromoblastomycosis Chromoblastomycosis is a long-term fungal infection of the skin and subcutaneous tissue (a chronic subcutaneous mycosis). It can be caused by many different types of fungi which become implanted under the skin, often by thorns or splinters. C ...
, a chronic fungal infection localized to skin and
subcutaneous tissue The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and macr ...
. The disease was first described by Alexandrino Pedroso in 1911. The fungus infects the host through the traumatic implantation of sexual spores known as
conidia A conidium ( ; ), sometimes termed an asexual chlamydospore or chlamydoconidium (), is an asexual, non-motile spore of a fungus. The word ''conidium'' comes from the Ancient Greek word for dust, ('). They are also called mitospores due to the ...
or hyphal fragments. Once introduced in the subcutaneous tissues, the
propagule In biology, a propagule is any material that functions in propagating an organism to the next stage in its life cycle, such as by dispersal. The propagule is usually distinct in form from the parent organism. Propagules are produced by organisms ...
s germinate to establish an invasive
mycelium Mycelium (plural mycelia) is a root-like structure of a fungus consisting of a mass of branching, thread-like hyphae. Fungal colonies composed of mycelium are found in and on soil and many other substrate (biology), substrates. A typical single ...
associated with sclerotic cells. This proliferation manifests as a well-defined, chronically progressive, crusted
ulceration An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
of the skin known as
chromoblastomycosis Chromoblastomycosis is a long-term fungal infection of the skin and subcutaneous tissue (a chronic subcutaneous mycosis). It can be caused by many different types of fungi which become implanted under the skin, often by thorns or splinters. C ...
. Clinically it is often misdiagnosed as
squamous cell carcinoma Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the ...
.


Histology

The disease is characterized by the appearance of spherical, brownish yellow cells with thick, darkly pigmented walls. The presence of the agent is associated with host cell proliferation and enlargement known as
hyperplasia Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferati ...
localized to the
stratified squamous epithelium A stratified squamous epithelium consists of squamous (flattened) epithelial cells arranged in layers upon a basal membrane. Only one layer is in contact with the basement membrane; the other layers adhere to one another to maintain structural i ...
and the formation of mycotic
granuloma A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious ...
s. Sclerotic bodies are present both extracellularly and intracellularly throughout the affected tissue and are a defining feature of chromoblastomycosis. The melanin content of sclerotic bodies may be important in the establishment of host immune responses.


Risk factors for infection

Farmers in Central and South America are most susceptible to chromoblastomycosis due to ''F. pedrosoi''. Infection often occurs in the upper body and legs of agricultural laborers since these areas are more prone to exposure to infected soil, plant debris or other fomites. The sex ratio of disease is globally variable. In Brazil, the agent has shown a 4:1 proclivity for men, likely as a function of exposure differences relating to work and lifestyle, while Japanese infections have shown evenly distributed infection rates between the sexes.


Treatment

Infections by ''F. pedrosoi'' are more difficult to treat than those of ''F. monophora''. In severe cases, treatment is quite complex and involves a combination of antifungal drug therapy and surgical excision. Antifungal agents like
itraconazole Itraconazole, sometimes abbreviated ITZ, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, blastomycosis, coccidioidomycosis, histoplasmosis, and paracoccidioidomycosis. It may be given by mouth ...
and
terbinafine Terbinafine, sold under the brand name Lamisil among others, is an antifungal medication used to treat pityriasis versicolor, fungal nail infections, and ringworm including jock itch and athlete's foot. It is either taken by mouth or applied to ...
are commonly used. Surgery is often used to treat small, localized infections, although
cryotherapy Cryotherapy, sometimes known as cold therapy, is the local or general use of low temperatures in medical therapy. Cryotherapy may be used to treat a variety of tissue lesions. The most prominent use of the term refers to the surgical treatment, s ...
has been suggested an alternative approach. Topical application of
amphotericin B Amphotericin B is an antifungal medication used for serious fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candidiasis, coccidioidomycosis, and cryptococcosis. Fo ...
followed by long-term administration of oral antifungal therapy has been shown to be effective in the treatment of corneal chromoblastomycosis from ''F. pedrosoi''. The diagnosis and treatment of chromoblastomycosis by ''F. pedrosoi'' remains clinically challenging due to the relative rarity of the disease, its slow, chronic nature, the absence of clinical features readily differentiating it from other more common diseases such as squamous cell carcinoma, the restricted nature of therapies, and the lack of literature.


References

{{Taxonbar, from=Q5465077 Eurotiomycetes Fungi described in 1922 Fungi of Africa Fungi of Central America Fungi of South America