''Aspergillus terreus'', also known as ''Aspergillus terrestris'', is a
fungus
A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from t ...
(mold) found worldwide in soil. Although thought to be strictly asexual until recently, ''A. terreus'' is now known to be capable of sexual reproduction.
This
saprotrophic
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 ( ...
fungus is prevalent in warmer climates such as tropical and subtropical regions.
Aside from being located in soil, ''A. terreus'' has also been found in habitats such as decomposing vegetation and dust.
''A. terreus'' is commonly used in industry to produce important organic acids, such as
itaconic acid
Itaconic acid, or methylidenesuccinic acid, is an organic compound. This dicarboxylic acid is a white solid that is soluble in water, ethanol, and acetone. Historically, itaconic acid was obtained by the distillation of citric acid, but currentl ...
and ''cis''-aconitic acid, as well as enzymes, like
xylanase
Endo-1,4-β-xylanase (EC 3.2.1.8, systematic name 4-β-D-xylan xylanohydrolase) is any of a class of enzymes that degrade the linear polysaccharide xylan into xylose, thus breaking down hemicellulose, one of the major components of plant cell ...
.
It was also the initial source for the drug mevinolin (
lovastatin
Lovastatin, sold under the brand name Mevacor among others, is a statin medication, to treat high blood cholesterol and reduce the risk of cardiovascular disease. Its use is recommended together with lifestyle changes. It is taken by mouth.
...
), a drug for lowering serum
cholesterol
Cholesterol is any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...
.
''Aspergillus terreus'' can cause
opportunistic infection in people with deficient immune systems. It is relatively resistant to
amphotericin B
Amphotericin B is an antifungal medication used for serious mycosis, fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candida infections, candidiasis, coccidioidomy ...
, a common antifungal drug.
''Aspergillus terreus'' also produces aspterric acid and
6-hydroxymellein, inhibitors of
pollen development in ''
Arabidopsis thaliana''.
Appearance
''Aspergillus terreus'' is brownish in colour and gets darker as it ages on culture media.
On
Czapek or malt extract agar (MEA) medium at , colonies have the conditions to grow rapidly and have smooth-like walls. In some cases, they are able to become floccose, achieving hair-like soft tufts.
Colonies on malt extract agar grow faster and sporulate more densely than on many other media.
''Aspergillus terreus'' has conidial heads that are compact, biseriate, and densely columnar, reaching 500 × 30–50 μm in diameter. Conidiophores of ''A. terreus'' are smooth and
hyaline up to 100–250 × 4–6 μm in diameter. The conidia of ''A. terreus'' are small, about 2 μm in diameter, globose-shaped, smooth-walled, and can vary from light yellow to hyaline.
Unique to this species is the production of aleurioconidia, asexual spores produced directly on the hyphae that are larger than the phialoconidia (e.g. 6–7 μm in diameter). This structure might be influential in the way ''A. terreus'' presents itself clinically as it can induce elevated inflammatory responses.
This fungus is readily distinguished from the other species of ''
Aspergillus
' () is a genus consisting of several hundred mold species found in various climates worldwide.
''Aspergillus'' was first catalogued in 1729 by the Italian priest and biologist Pier Antonio Micheli. Viewing the fungi under a microscope, Mic ...
'' by its cinnamon-brown colony colouration and its production of aleurioconidia. ''A. terreus'' is a thermotolerant species since it has optimal growth in temperatures between , and maximum growth within .
Ecology
''Aspergillus terreus'', like other species of'' Aspergillus'', produces spores that disperse efficiently in the air over a range of distances.
The morphology of this fungus provides an accessible way for spores to disperse globally in air current.
Elevation of the sporulating head atop a long stalk above the growing surface may facilitate spore dispersal through the air.
Normally, spores in fungi are discharged into still air, but in ''A. terreus'', it resolves this problem with a long stalk and it allows the spores to discharge into air currents like wind.
In turn, ''A. terreus'' has a better chance to disperse its spores amongst a vast geography which subsequently explains for the worldwide prevalence of the fungus.
Despite ''A. terreus'' being found worldwide in warm, arable soil, it has been located in many different habitats such as compost and dust.
Eventually, the dispersed fungal spores come into contact with either liquid or solid material and settle onto it, but only when the conditions are right do the spores germinate. One of the conditions important to the fungus is the level of moisture present in the material. The lowest
water activity
Water activity (''aw'') is the partial vapor pressure of water in a solution divided by the standard state partial vapor pressure of water. In the field of food science, the standard state is most often defined as pure water at the same tempe ...
(A
w) capable of supporting growth of the fungus has been reported as 0.78.
Tolerance of relatively low A
w conditions may explain, in part, the ubiquitous nature of this species given its ability to grow is a wide array of places.
The soil of potted plants is one common habitat supporting the growth of ''A. terreus'', and colonized soils may be important reservoirs of
nosocomial
A hospital-acquired infection, also known as a nosocomial infection (from the Greek , meaning "hospital"), is an infection that is acquired in a hospital or other health care facility. To emphasize both hospital and nonhospital settings, it is ...
infection.
Other habitats include cotton, grains, and decomposing vegetation.
Genome
The Broad Fungal Genome Initiative funded by the
National Institute of Allergy and Infectious Disease
The National Institute of Allergy and Infectious Diseases (NIAID, ) is one of the 27 institutes and centers that make up the National Institutes of Health (NIH), an agency of the United States Department of Health and Human Services (HHS). NIAID's ...
carried out the sequencing ''A. terreus'' in 2006. The result was 11.05 × genome sequence coverage. ''A. terreus'' contains 30-35 Mbp and roughly 10,000 protein-coding genes.
Identification of virulence determinants within the genome of ''A. terreus'' may facilitate the development of new approaches to the treatment of ''A. terreus''-related diseases. In addition, because ''A. terreus'' is resistant to the common antifungal drug amphotericin B, the mechanisms underlying its resistance may be better understood by genome-level investigation.
The
polyketide synthase
Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynth ...
gene ''
atX
ATX (Advanced Technology eXtended) is a motherboard and power supply configuration specification developed by Intel in 1995 to improve on previous de facto standards like the AT design. It was the first major change in desktop computer enclo ...
'' produces
6-Methylsalicylic acid in ''A. terreus''.
Infection
''Aspergillus terreus'' is not as common as other ''Aspergillus'' species to cause opportunistic infections in animals and humans. However, the incidence of ''A. terreus'' infection is increasing more rapidly than any other ''Aspergillus'' and for this reason it is considered an emerging agent of infection.
As an opportunistic pathogen, it is able to cause both systemic and superficial infections.
Inhalation of fungal spores, which travel down along the respiratory tract, cause the typical respiratory infection. Other infections could also occur, such as
onychomycosis
Onychomycosis, also known as tinea unguium, is a fungal infection of the nail. Symptoms may include white or yellow nail discoloration, thickening of the nail, and separation of the nail from the nail bed. Toenails or fingernails may be affected, ...
and
otomycosis
Otomycosis is a fungal ear infection, a superficial mycotic infection of the outer ear canal. It is more common in tropical countries. The infection may be either subacute or acute and is characterized by malodorous discharge, inflammation ...
.
''A. terreus'' has the ability to cause serious effects in
immunocompromised
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
patients who lack specific immune cells. Specifically, prolonged
neutropenia predisposes humans and animals to this fungal disease.
''Aspergillus terreus'' has no adaptation in terms of changing its physical structure when infecting a human or animal host. The fungus continues to grow as the characteristic hyphae filaments. Other pathogenic fungi usually switch over to a different growth stage, mycelia-to-yeast conversion, to best suit their new environment. This process does not occur in ''A. terreus''.
Plants
For decades, ''A. terreus'' has been used in agriculture as a means to control pathogenic fungi from destroying crops. However, during the late 1980s, researchers described ''A. terreus'' as a fungal pathogen in plants. Crops such as
wheat
Wheat is a grass widely cultivated for its seed, a cereal grain that is a worldwide staple food. The many species of wheat together make up the genus ''Triticum'' ; the most widely grown is common wheat (''T. aestivum''). The archaeologi ...
and
ryegrass
''Lolium'' is a genus of tufted grasses in the bluegrass subfamily (Pooideae). It is often called ryegrass, but this term is sometimes used to refer to grasses in other genera.
They are characterized by bunch-like growth habits. ''Lolium'' i ...
were shown to acquire disease following ''A. terreus'' infection. More recently, researchers have discovered the species can also cause foliar blight of potatoes. This was first described in India.
''A. terreus'' infection can have important implications because potatoes are considered the third-most important food crop in the world.
''Aspergillus terreus'' has also been shown to disrupt the male sexual reproductive cycle in the plant model organism ''Arabidopsis thaliana''. Its
secondary metabolites
Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by any lifeform, e.g. bacteria, fungi, animals, or plants, which are not directly involved in the nor ...
, aspterric acid and 6-hydroxymellein, released from the fungus inhibit the production of pollen, the male gamete in plants. Since ''Arabidopsis thaliana'' cannot reproduce, it is sterile and cannot contribute offspring to the next generation. Ultimately, this has an effect on genetic diversity in the plant species.
Animals
''Aspergillus terreus'' can cause infection in animals, but it is contained to a few species such as dogs and cattle. Widely, ''A. terreus'' is found to cause mycotic abortion in cattle.
In dogs, especially in the
German Shepherd
The German Shepherd or Alsatian is a German breed of working dog of medium to large size. The breed was developed by Max von Stephanitz using various traditional German herding dogs from 1899.
It was originally bred as a herding dog, for ...
breed, this fungus is also responsible for
sinusitis
Sinusitis, also known as rhinosinusitis, is inflammation of the mucous membranes that line the sinuses resulting in symptoms that may include thick nasal mucus, a plugged nose, and facial pain. Other signs and symptoms may include fever, head ...
.
It can further affect dogs through its dissemination. It can affect other parts of the body, including organs such as the spleen and kidneys.
Also, the bone can be affected by ''A. terreus'' which could lead to spinal
osteomyelitis
Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...
.
Very few animal models exhibit ''A. terreus'' infections. Some successful animal models include the mouse and rabbit where ''A. terreus'' has formed pulmonary
aspergillosis
Aspergillosis is a fungal infection of usually the lungs, caused by the genus ''Aspergillus'', a common mould that is breathed in frequently from the air around, but does not usually affect most people. It generally occurs in people with lung di ...
. These studies are important because it provides evidence that this fungal infection can cause disease.
Humans
In humans, ''A. terreus'' is less commonly encountered as a pathogen than other ''Aspergillus'' species, most notably ''
A. fumigatus,
A. flavus'' and ''
A. niger''.
Although less frequently seen in clinical samples, ''A. terreus'' displays evidence of amphotericin B resistance which correlates to a high rate of dissemination and an overall poor prognosis.
''Aspergillus terreus'' causes opportunistic infections mostly in immunocompromised people such as COPD patients who are taking
corticosteroids, cancer patients receiving chemotherapy treatment, or HIV/AIDS patients.
In an
immunocompetent
In immunology, immunocompetence is the ability of the body to produce a normal immune response following exposure to an antigen. Immunocompetence is the opposite of immunodeficiency (also known as ''immuno-incompetence'' or being ''immuno-compro ...
individual, the inhalation of spores initiates an immediate release of macrophages and neutrophils. In an immunosuppressed individual, this response is less vigorous. Most of these individuals suffer from neutropenia, which makes them less capable of defending themselves. In addition, ''A. terreus'' releases toxic metabolites that attack immune cells like neutrophils which provide the suitable conditions for the fungus to thrive.
''Aspergillus terreus'' infection can lead to superficial infections in humans. These affect the outside layer of the body. It is commonly isolated from onychomycosis which is infection of human skin and nails.
The incidence of onychomycosis as a result of ''A. terreus'' (not the common agent
dermatophyte
Dermatophyte (from Greek '' derma'' "skin" ( GEN ''dermatos'') and ''phyton'' "plant") is a common label for a group of fungus of ''Arthrodermataceae'' that commonly causes skin disease in animals and humans. Traditionally, these anamorphic (a ...
) is increasing. This happens to be the most frequently reported superficial infection in clinics and hospitals.
Another common superficial infection caused by ''A. terreus'' includes
otomycosis
Otomycosis is a fungal ear infection, a superficial mycotic infection of the outer ear canal. It is more common in tropical countries. The infection may be either subacute or acute and is characterized by malodorous discharge, inflammation ...
(ear infection), which is mostly isolated from patients who had recent surgical operations.
In addition, ''A. terreus'' infection can also result in four main systemic disease outcomes:
*
Allergic bronchopulmonary aspergillosis
Allergic bronchopulmonary aspergillosis (ABPA) is a condition characterised by an exaggerated response of the immune system (a hypersensitivity response) to the fungus ''Aspergillus'' (most commonly ''Aspergillus fumigatus''). It occurs most oft ...
*''Aspergillus'' bronchitis and invasive ''Aspergillus'' tracheobronchitis
*Invasive (pulmonary) aspergillosis
*Disseminated aspergillosis
Though all four disease outcomes can impose a great health risk to humans; invasive aspergillosis tends to result in the highest mortality and morbidity rates in humans.
Epidemiology studies have shown the incidence of ''A. terreus'' in causing invasive aspergillosis has increased relative to other species in the genus.
''A. terreus'' infection causes 100% mortality rate in people who acquire invasive aspergillosis. Compared to 20 other ''Aspergillus'' species, ''A. terreus'' infection is associated with the poorest prognosis and high mortality. In fact, invasive aspergillosis has been named as the leading cause of death in
leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
and
stem cell transplantation patients.
Treatment and prevention
Treatment of ''A. terreus'' is clinically challenging due to its nearly complete resistance to
amphotericin B
Amphotericin B is an antifungal medication used for serious mycosis, fungal infections and leishmaniasis. The fungal infections it is used to treat include mucormycosis, aspergillosis, blastomycosis, candida infections, candidiasis, coccidioidomy ...
, the fallback drug for serious fungal infections.
However, some newer drugs, such as
voriconazole
Voriconazole, sold under the brand name Vfend among others, is an antifungal medication used to treat a number of fungal infections. This includes aspergillosis, candidiasis, coccidioidomycosis, histoplasmosis, penicilliosis, and infections by ...
,
posaconazole
Posaconazole, sold under the brand name Noxafil among others, is a triazole antifungal medication.
It was approved for medical use in the United States in September 2006, and is available as a generic medication.
Medical uses
Posaconazole is u ...
, and
caspofungin, have shown promise in treating this agent.
The laboratory identification of ''A. terreus'' from clinical specimens can also be difficult. Currently, no rapid immunological tests are available for this species, and its correct identification remains dependent on culture. ''A. terreus'' strains have a tendency to mutate while in the animal host, resulting in a substantial reduction or loss of characteristic spore heads in primary culture. Such strains continue to produce small aleuroconidia similar in appearance to the aleurioconidia of ''Blastomyces dermatitidis''.
In one study, nearly a third of ''A. terreus'' infections in hospitals were found to be associated with the presence of potted plants.
Elimination of potted plants in the rooms of immunodeficient patients may have a role in prevention of illness. ''A. terreus'' has also been described in many studies as common to the hospital setting because of outside hospital construction and renovations. The amount of soil and debris reintroduced into the air is capable of travelling through the air and infecting immunosuppressed patients.
A simple way to take preventive action is to provide good air filtration and ventilation throughout the hospital rooms. Elimination of inoculum is key to the prevention of nosocomial infection by ''A. terreus''.
Industrial uses
''Aspergillus terreus'' produces a number of secondary metabolites and
mycotoxins
A mycotoxin (from the Greek μύκης , "fungus" and τοξίνη , "toxin") is a toxic secondary metabolite produced by organisms of kingdom Fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' ...
, including territrem A,
citreoviridin
Citreoviridin is a mycotoxin which is produced by ''Penicillium'' and ''Aspergillus
' () is a genus consisting of several hundred mold species found in various climates worldwide.
''Aspergillus'' was first catalogued in 1729 by the Italian pr ...
,
citrinin,
gliotoxin
Gliotoxin is a sulfur-containing mycotoxin that belongs to a class of naturally occurring 2,5-diketopiperazines produced by several species of fungi, especially those of marine origin. It is the most prominent member of the epipolythiopiperazi ...
,
patulin
Patulin is an organic compound classified as a polyketide. It is a white powder soluble in acidic water and in organic solvents. It is a lactone that is heat-stable, so it is not destroyed by pasteurization or thermal denaturation.http://www.s ...
,
terrein, terreic acid, and terretonin.
The fungus also produces a secondary metabolite called
lovastatin
Lovastatin, sold under the brand name Mevacor among others, is a statin medication, to treat high blood cholesterol and reduce the risk of cardiovascular disease. Its use is recommended together with lifestyle changes. It is taken by mouth.
...
, a potent drug for lowering blood cholesterol levels in humans and animals. It is an inhibitor to one of the enzymes responsible in the catalyzing steps in cholesterol biosynthesis. Lovastatin is typically produced within fermentation conditions of the fungus. Fast growth of filamentous hyphae in the species ''A. terreus'' can result in low lovastatin production. To increase the production of this metabolite ''A. terreus'' requires important nutrients during fermentation. In this case, carbon and nitrogen are very important in fermentation productivity which in turn also increases the biomass of the metabolite lovastatin.
''A. terreus'' strains use
glycerol
Glycerol (), also called glycerine in British English and glycerin in American English, is a simple triol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids known ...
and
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
as their best carbon sources for lovastatin production.
It is also used to produce the drug
simvastatin
Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of hear ...
that is chemically related to lovastatin.
References
{{Taxonbar, from=Q3798237
Fungi described in 1918
terreus
Taxa named by Charles Thom