Cladophialophora Arxii
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''Cladophialophora arxii'' is a black yeast shaped
dematiaceous “Black yeasts”, sometimes also black fungi, dematiaceous fungi, microcolonial fungi or meristematic fungi is a diverse group of slow-growing microfungi which reproduce mostly asexually (fungi imperfecti). Only few genera reproduce by budding ...
fungus that is able to cause serious phaeohyphomycotic infections. ''C. arxii'' was first discovered in 1995 in Germany from a 22-year-old female patient suffering multiple granulomatous tracheal tumours. It is a clinical strain that is typically found in humans and is also capable of acting as an opportunistic fungus of other vertebrates Human cases caused by ''C. arxii'' have been reported from all parts of the world such as
Germany Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...
and
Australia Australia, officially the Commonwealth of Australia, is a Sovereign state, sovereign country comprising the mainland of the Australia (continent), Australian continent, the island of Tasmania, and numerous List of islands of Australia, sma ...
. The genus ''Cladophialophora'' comprises four different lineages, one of the main lineages belongs to the family of ''
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 '' ...
''. Within this lineage there are two major clades of the two one is called the ''bantiana'' clade in which ''C. arxii'' can be found. ''C.arxii'' is typically slow growing and is capable of growing at higher temperatures compared to other fungi with its maximal growth temperature reaching 42°.


History and taxonomy

''Cladophialophora arxii'' was first discovered in a tracheal granulomatous tumour of a 22-year-old female in
Berlin Berlin ( , ) is the capital and largest city of Germany by both area and population. Its 3.7 million inhabitants make it the European Union's most populous city, according to population within city limits. One of Germany's sixteen constitue ...
,
Germany Germany,, officially the Federal Republic of Germany, is a country in Central Europe. It is the second most populous country in Europe after Russia, and the most populous member state of the European Union. Germany is situated betwe ...
in 1995. It was originally considered to be ''C. borelli'' due to the similarity in structural appearance to ''C. arxii''. The fungus was considered to be of the genus ''
Cladosporium ''Cladosporium'' is a genus of fungi including some of the most common indoor and outdoor molds. Species produce olive-green to brown or black colonies, and have dark-pigmented conidia that are formed in simple or branching chains. Many species ...
.'' The genus ''Cladosporium'' was first discovered in 1816, several human pathogenic species belonging to ''Cladosporium'' are now classified as the genus ''Cladophialophora''. The genus ''Cladophialophora'' mainly consists of species of melanized hyphomycetes that are found within human hosts. ''C. arxii'' within the genus ''Cladophialophora'' was named after Dr. J.A von Arx, a Dutch mycologist, for his efforts in classify the genus ''Cladosporium''.


Phylogeny

The genus ''Cladophialophora'' currently contains seven different species that are capable of causing disease in humans, ''C.arxii'' included. ''Cladophialophora'' consists of four different lineages: one lineage belonging to 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 other pertaining to a group of rock-dwelling strains. The majority of the human opportunistic fungi of ''Cladophialophora'' can be found within ''Herpotrichiellaceae'' which forms two major clades. The first clade, is known as the ''C. carrionii''-clade and contains the species ''C. carrionii'' and ''C. boppii''. The second clade, the ''C. bantiana'' clade includes the species ''C. bantiana, C. devriesii, C. mycetomatis, C. immunda, C. emmonsii, C. saturnica'' and ''C. arxii.'' It has been found that the environmental strain ''C. minourae'' is a sister strain to ''C. arxii''


Habitat

''Cladophialophora'' is a genus of black yeast fungi whose natural habitat consists of soil and rotting plant material. Several of the species pertaining to the ''Cladophialophora'' have been reported in both tropical and subtropical regions of the world. ''Cladophialophora arxii'' is a clinical strain that has generally been found in humans ''C. arxii'' is also capable of acting as an opportunistic fungus of other vertebrates.


Growth and morphology

''C. arxii'' is a slow growing fungus that grows to about 36–40 mm in size when cultured on a growth medium of SDA agar and PDA agar at 25 °C over a span of 35 days. The colonies formed contained dark grey aerial
hyphae A hypha (; ) is a long, branching, filamentous structure of a fungus, oomycete, or actinobacterium. In most fungi, hyphae are the main mode of vegetative growth, and are collectively called a mycelium. Structure A hypha consists of one or ...
and black-brown coloured
hyphae A hypha (; ) is a long, branching, filamentous structure of a fungus, oomycete, or actinobacterium. In most fungi, hyphae are the main mode of vegetative growth, and are collectively called a mycelium. Structure A hypha consists of one or ...
located on the margins of the SDA agar. On the PDA the colonies were dark black-brown with felty radial furrows. The fungus contained olive brown septated hyphae with both lateral and termina
acropetal
conidial 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 t ...
chains with branching. The overall morphology of the conidia of ''C.arxii'' are very similar t
''Cladophialophora devriesii''
the conidial chains of ''C.arxii'' are longer. Additionally, the conidial chains are fragile and borne on denticles. The conidia of ''C.arxii'' are pale brown, smooth, thick walled with a lemon-spindle shaped morphology. Initially the fungus contained
muriform
cells from tissue samples but following corticosteroid therapy the cells changed their shape and become irregularly shaped hyphae.


Physiology

The optimal growth temperature of the ''Cladophialophora'' species is from 27 to 30 °C but are capable of growing anywhere between 9-37 °C. ''C. arxii'' grows optimally at 37 °C with the maximum temperature it can grow at being 42 °C. ''C. arxii'' has an optimal production of non-septate swollen cells at a pH of 4–5. ''C. arxii'' is meso-erythritol and galactitol assimilated but is unable to assimilate on ethanol. Furthermore, it is not able to assimilate methyl-alpha-glucoside, soluble starch, glycerol, meso-erythritol, myoinositol or succinate.


Clinical relevance

Is a
dematiaceous “Black yeasts”, sometimes also black fungi, dematiaceous fungi, microcolonial fungi or meristematic fungi is a diverse group of slow-growing microfungi which reproduce mostly asexually (fungi imperfecti). Only few genera reproduce by budding ...
fungus that causes severe phaeohyphomycotic infections. It is fungus that is rarely seen, was the cause of granulomatous tumours in the trachea of the first patient that was diagnosed with this fungus in 1995. The fungus was treated with 5-FC,
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 ...
, an
itraconazole
''C. arxii'' was assumed to be the cause of subcutaneous phaeohyphomycosis of an ulcer in a 68-year-old woman, however, these results were not definitive Shortly after in 2001, it was believed that ''C. arxii'' was responsible for causing both cerebral and lung phaeohyphomycosis in a 30-year-old African women following a heart transplant. Additionally, it was the cause of femoral osteomyelitis in a 20-year-old man. Treatment of the osteomyelitis included surgical debridement, itraconazole, and
interferon gamma Interferon gamma (IFN-γ) is a dimerized soluble cytokine that is the only member of the type II class of interferons. The existence of this interferon, which early in its history was known as immune interferon, was described by E. F. Wheelock ...
treatment. Finally, the most recently reported case of ''C. arxii'' was seen in Australia with the patient suffering from a pulmonary
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 ...
.


Treatment

Several anti fungal drugs have been shown to be successful in treating ''C. arxii'' such 5-FC, amphotericin B, itraconazole, and interferon gamma treatment. Additionally, most of these antifungal drugs are usually accompanied by surgical procedures such as surgical debridement. Furthemore, in vitro studies have shown that combination therapy with
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 ...
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 ...
have synergistic effects against ''C. arxii''. 5-FC and itraconazole have also shown synergistic effects when targeting infections caused by ''C. arxii''.


References

{{Taxonbar , from = Q10454334 Eurotiomycetes