Aspergillus terreus, also known as Aspergillus terrestrius, is an asexual fungus (mold) found worldwide in soil. This saprotrophic fungus is prevalent in warmer climates such as tropical and sub-tropical regions. Aside from being located in soil, A. terreus has also been found in habitats such as decomposing vegetation and dust. Aspergillus terreus is commonly used in industry to produce important organic acids, such as itaconic acid and cis-aconitic acid as well as enzymes, like xylanase. It was also the initial source for the drug mevinolin (lovastatin), a drug for lowering serum cholesterol.
Aspergillus terreus can cause opportunistic infection in people with deficient immune systems. It is relatively resistant to amphotericin B, a common antifungal drug. Aspergillus terreus also produces aspterric acid and 6-hydroxymellein, inhibitors of pollen development in Arabidopsis thaliana.
Aspergillus terreus is brownish in colour and gets darker as it ages on culture media. On Czapek or Malt Agar Extract (MAE) medium at 25 °C, 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 Aspergillus 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 are larger than the phialoconidia (e.g. 6–7 µm in diameter). It is thought that 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 in the Aspergillus genus because of its unique cinnamon-brown colour.Aspergillus terreus can be classified as a thermotolerant species since it has optimal growth in temperatures between 35–40 °C, and maximum growth within 45–48 °C.
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. Specifically, it is the characteristic long stalk of the fungus which allows for the spores at the conidia to travel great distances. 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 current 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 it only when the conditions are right that the spores germinate. One of the conditions important to the fungus, A. terreus, is the level of moisture present in the material. The water activity (aw) of the fungus is reported to be as low as 0.78. This relatively low aw value 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 it has been suggested that colonized soils may be important reservoirs of nosocomial infection. Other habitats include cotton, grains and decomposing vegetation.
The Broad Fungal Genome Initiative funded by the National Institute of Allergy and Infectious Disease (NIAID) carried out the sequencing A. terreus in 2006. The result was 11.05 × genome sequence coverage. Aspergillus 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 anti-fungal drug amphotericin B, the mechanisms underlying its resistance may be better understood by genome-level investigation.
Aspergillus terreus is not as common as other Aspergillus species to cause opportunistic infections in animals and humans. However, it has been noted that the incidence of A. terreus infection is increasing more rapidly than any other Aspergillus. As a result this fungus is commonly referred to as an emerging infection.
As an opportunistic agent, it is able to cause both systemic and superficial infections. It is through inhalation of fungal spores,which travel down along the respiratory tract, that cause the typical respiratory infection. Other infections could also occur such as onychomycosis and otomycosis. Aspergillus terreus has the ability to cause serious effects in immunocompromised patients who lack specific immune cells. Specifically, it is prolonged neutropenia that 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.
For decades Aspergillus 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. It was shown that crops such as wheat and ryegrass acquired disease following A. terreus infection. More recently researchers have discovered that the species can also cause foliar blight of potato. This was first described in India. It is important to understand the implications Aspergillus terreus infection can have 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. It is the secondary metabolites, aspterric acid and 6-hydroxymellein, released from the fungus that inhibits 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.
Aspergillus terreus can cause infection in animals but it is contained to a few species such as dogs and cows. Widely, A. terreus is found to cause mycotic abortion in cattle. In dogs, especially in the German Shepherd breed, this fungus is also responsible for sinusitis. Aspergillus terreus 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.
There have been very few animal models with A. terreus infections. Some successful animal models include the murine and rabbit where A. terreus has formed pulmonary aspergillosis. These studies are important because it provides evidence that this fungal infection can cause disease.
In humans, A. terreus is less commonly encountered as a pathogen than other species, most notably Aspergillus fumigatus, Aspergillus flavus and Aspergillus 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 individual, once the fungal pathogen is inhaled, they would respond immediately via the first line of immune defense. This defense system includes the release of macrophages and neutrophils in an attempt to clear the fungus. In an immunosuppressed individual this response would not be initiated as vigorously as a healthy person. Most of these individuals suffer from neutropenia which makes them less capable of defending themselves because neutrophil count is low. In addition, A. terreus releases toxic metabolites that attack immune cells like neutrophils which provides the suitable conditions for the fungus to thrive in.
Aspergillus terreus infection can lead to superficial infections in humans. These affect the outside layer of the body. Aspergillus terreus 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 agentDermatophyte) 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 (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:
• Aspergillus bronchitis and invasive Aspergillus tracheobronchitis
• Invasive (pulmonary) aspergillosis
• Disseminated aspergillosis
Even 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 that the incidence of A. terreus in causing invasive aspergillosis has increased relative to other species in the genus. Aspergillus terreus infection causes 100% mortality rate in people who acquire invasive aspergillosis. Compared to twenty other Aspergillus species A. terreus has the weakest prognosis which ultimately leads to death. In fact, invasive aspergillosis has been named as the leading cause of death in leukemia and stem cell transplantation patients.
Treatment and prevention
Aspergillus terreus is a threat to animal and human species because of its complete resistance to amphotericin B, a crucial treatment for fungal infections. Aside from people having no benefits with this drug it is also a very uncomfortable treatment process to experiece. Most often, individuals are injected with amphotericin B and this causes uncontrollable muscular shaking. Newer drug treatments such as voriconazole, posaconazole, and caspofungin have been produced which yield better results when compared to amphotericin B. The main goal of these drug treatments is for the infected individual to recover from neutropenia that was initially caused by the secondary metabolites released from the fungus.
Identification of A. terreus infection is relatively slow. There are no rapid tests and antigen tests such as galactomannan and β-glucan do not distinguish between species. Furthermore, lab mycologists often mistake the A. terreus species as a Blastomyces dermatitidis. The reason for the confusion is the ability of A. terreus strains to mutate while inhabiting the animal host. During this time the fungus can lose their dramatic spore heads. The only recognizable structure left behind is their small aleuroconidia. This looks very similar to the conidia of the Blastomyces dermatitidis which leads to the wrong identification of the fungus. This sometimes leads physicians to prescribe the wrong anti-fungal drugs to the infected patient. Ultimately, the treatment of Aspergillus terreus is very difficult. In turn, the fungal infections persists.
In order to reduce the number of new A. terreus infections there has to be preventative measures that try to decrease the dispersal of fungal spores. By regulating areas where the fungus is known to be prevalent it could result in decrease of infections. It is known that Aspergillus terreus can be classified as a nosocomial infection.
In a study that was done over a period of five years it found that 30% of A. terreus infections were associated with hospital plants. Many immunocompromised patients get sick by the fungus during their stay at the hospital. A simple prevention method is decreasing the presence of potted plants in the rooms of immune deficient patients. Aspergillus terreus has also been described in many studies as common to the hospital setting becuase of outside hospital construction and renovations. The amount of dirt and debris that is reintroduced into the air is capable of travelling through the air and infecting immunosuppressed patients. A simple way to take preventative action is to provide good air filtration and ventilation throughout the hospital rooms.
Aspergillus terreus produces a number of secondary metabolites and mycotoxins including territrem A, citreoviridin, citrinin, gliotoxin, patulin, terrein, terreic acid and terretonin. The fungus also produces a secondary metabolite called lovastatin, 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. It has been shown that 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. It has been found that Aspergillus terreus strains use glycerol and glucose as their best carbon sources for lovastatin production.
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