m36 Aspergillus terreus

Nature

Aspergillus terreus is a filamentous thermotolerant fungus (1, 2). A. terreus is pathogenic to human and plant species (3). Whereas A. fumigatus is the most prevalent pathogen of the genera, causing 67‒73% of infections in man, A. terreus is the causative organism in 3‒4% of Aspergillus infections (1). Distinguishing morphological features of A. terreus include relatively small conidial heads (2.0‒3.5 µm) and tan color colonies (4). A. terreus is one of a few species that produce lateral conidia (aleuroconidia), which have been shown to induce inflammation in an invasive aspergillosis murine model (5).

A. terreus is an opportunistic pathogen and is associated with a high rate of dissociative infection and poor outcome, predominantly in patients with prolonged neutropenia, allogenic haematopoietic stem cell transplant, solid organ transplant, inherited or acquired immunodeficiencies and corticosteroid use (5, 6). A. terreus is a cause of allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity syndrome in patients with asthma and cystic fibrosis (3, 7). A. terreus is also classified as resistant to amphotericin B, meaning the clinical management of A. terreus associated disease can be challenging (1, 5). A. terreus is also a major plant pathogen which is estimated to destroy over 125 million tons of crops such as rice, wheat and potato globally every year (8).

A. terreus has economic and pharmaceutical importance. As well as its use in the fermentation industry for producing itaconic acid and itatartaric acid, its secondary metabolites are used to manufacture clinically valuable drugs, including lovastatin, antitumor metabolites and cyclosporine A (9).

Taxonomy 

Allergenic molecules

Three A. terreus specific allergens have been recognized by the WHO/IUIS Allergen Nomenclature Sub-committee. In a study that used a proteomic approach to identify A. terreus allergens, the allergen Asp t 36, a triosephosphate isomerase was characterized and purified in its native state and recombinant form. Both natural TPI and recombinant TPI resulted in a significant amount of IgE binding in A. terreus-sensitized patients (P<0.05), indicating the potential to be a major allergen. The authors stated that Asp t 36 had potential for use in both diagnosis of A. terreus hypersensitivities and as a target for immunotherapy (3).

Another potential allergen, glycolytic enolase, has been identified on the surface of A. terreus. Glycolytic enolase is an intracellular enzyme required for glycolysis and gluconeogenesis. However, surface localization results in its exposure to the host immune system (21).

Table adapted from (20).

Cross-reactivity

Several studies have demonstrated cross-reactivity of A. terreus extract with specific allergens of other Aspergillus spp. One study, which analyzed type III hypersensitivity responses, found that levels of A. fumigatus specific IgG were significantly correlated with A. terreus specific IgG (22), indicating cross-reactivity. Similarly, a study found that patients positive for A. terreus specific IgE were all found to be positive to A. fumigatus specific antigen, although it is thought that A. terreus is less cross-reactive with A. fumigatus than A. flavus (17).

TPI homologues are found in crustaceans and shellfish and are a common cause of food allergy in these species (3). The discovery that Asp t 36 is a homologue to crustaceans and shellfish allergens could anticipate further examples of cross-reactivity between fungal and arthropod allergens (3, 23). Karmakar’s group demonstrated significant sequence homology between Asp t 36 and Der f 25, an allergen specific to the dust mite Dermatophagoides farina, as well as triosephosphate isomerases from the cockroach Blatella germanica (3). They also found the sequence was highly conserved, and similarities were noted with the TPI of wheat, house dust mite and the German cockroach, with conservation of IgE binding epitopes and implicating high cross-reactivity with both phylogenetically related and unrelated species (3).