Table of Contents
- General Characteristics
- Habitat
- Morphology
- Cultural Characteristics
- Life Cycle
- Pathogenesis
- Clinical manifestation
- Laboratory diagnosis
- Treatment
- Prevention and Control
- References
General Characteristics of Aspergillus spp
- Aspergillus spp is commonly found in soil and exhibits a saprophytic mode of nutrition, obtaining nutrients from dead and decaying matter.
- The saprophytic nature of Aspergillus spp means they fully rely on environmental organic materials, enabling them to produce enzymes such as amylase, which breaks down complex compounds into simpler products that can be absorbed by the vegetative hyphae.
- High production of amylase enzymes allows Aspergillus spp to consistently decompose organic matter in their environment, increasing the availability of food materials that can be utilized for reproduction and growth.
- Aspergillus spp is a spore-forming mold fungus that reproduces asexually by producing spores known as conidia (singular: conidium).
- Conidia are abundantly present in the air and can be dispersed widely.
- When moisture, warmth, and nutrients are available, conidia can germinate, producing hyphae that eventually develop into fungal mycelium.
- Hyphal filaments enable the fungus to grow and reproduce effectively.
- During sporulation, conidial spores are produced in large quantities and released into the air, leading to constant inhalation by humans and animals, often in hundreds per day.
- Aspergillus spp can be pathogenic in humans, potentially causing severe allergic reactions and respiratory opportunistic fungal infections, collectively referred to as Aspergillosis, particularly in individuals with compromised immune systems.
- Common species of Aspergillus include:
- Aspergillus fumigatus
- Aspergillus niger
- Aspergillus flavus
- Aspergillus nidulans
- Aspergillus clavans
Habitat of Aspergillus fumigatus
- Aspergillus fumigatus is a fungus belonging to the Aspergillus group of fungi.
- Its ecological niche is in soil, where it survives and grows on organic debris.
- It is one of the most common, ubiquitous, airborne saprophytic fungi.
- It is predominantly present in the air and is therefore constantly inhaled in the form of conidia by humans and animals.
Morphology of Aspergillus fumigatus
- The morphology of Aspergillus fumigatus is characterized by its hyphal conidia and conidiophores.
- The conidia are green and spiked, with small projections covering their surface.
- Conidia measure approximately 2.5–3 µm in diameter.
- The surface of the conidia can be smooth or spiked (spinose).
- Conidia are produced in column-like chains that are basipetal (facing downwards) from green phialides measuring 6–8 µm by 2–3 µm in size.
- Some A. fumigatus strains produce white conidia due to the absence of pigment.
- Conidial chains are formed directly on broadly clavate vesicles, measuring 20–30 µm in diameter, in the absence of metulae (the outermost branches of a conidiophore from which flask-shaped phialides radiate).
Cultural Characteristics of Aspergillus fumigatus
- Aspergillus fumigatus is thermophilic, capable of growing at temperatures as high as 55 °C and surviving in temperatures up to 70 °C.
- It is a fast-growing fungus in culture.
- It grows well on basic fungal media, such as Sabouraud Dextrose Agar (SDA).
- It can produce colonies with colors ranging from white, yellow, yellow-brown, brown to black, or green.
- On Czapek-Dox agar at 25 °C, it forms colonies measuring approximately 4 ± 1 cm in diameter within one week.
Life Cycle of Aspergillus fumigatus
- Aspergillus fumigatus reproduces through an asexual sporulation process.
- When released spores, known as conidia, land on a surface with suitable growth conditions and nutrient availability, they germinate to form hyphae.
- The hyphae develop into both aerial hyphae and subsurface hyphae.
- Aerial hyphae give rise to conidiophores, which in turn produce phialides.
- Columnar phialides generate spores in the form of conidia, arranged in chains.
Pathogenesis of Aspergillus fumigatus
Aspergillus fumigatus is a highly ubiquitous fungus that disperses its spores in dense quantities, with humans and animals potentially inhaling more than 100 spores per day.
Transmission
- The primary mode of transmission is through inhalation of fungal spores (conidia).
- These spores are abundantly present in the environment and are continuously inhaled by humans.
- In individuals with weakened respiratory immunity, the inhaled spores can lead to opportunistic infections.
Host colonization
- In immunocompromised individuals, the inhaled conidia attach to epithelial cells that have been damaged by immune-suppressing factors such as corticosteroid drugs or radiation therapy, allowing colonization of the affected surfaces.
- A unique feature of A. fumigatus conidia is their ability to evade innate immune defenses, including respiratory tract cilia and the mucosal lining.
- This immune evasion is facilitated by secondary metabolites such as gliotoxin, helvolic acid, and fumagillin, which help bypass the mucociliary clearance system.
- Conidia bind to damaged epithelial cells and respiratory tract membranes via sialic acid, which also plays a role in the asexual reproduction of pathogenic Aspergillus species.
- Once attached, the conidia are engulfed by macrophages, forming a phagosome, where they can germinate while preventing apoptotic death of epithelial cells.
- The fungus produces protease enzymes to assist in lung tissue colonization and elastase enzymes to degrade host lung tissue.
Evading of macrophage mechanisms
- Acute inflammation can impair the effector functions of alveolar macrophages, enabling A. fumigatus to invade and kill these immune cells shortly after conidial germination.
- Conidial spores are recognized by macrophages through a surface carbohydrate complex known as β-(1,3)-glucan.
- This β-(1,3)-glucan binds to dectin receptors on alveolar macrophages, triggering phagocytosis and inflammation in alveolar and lung tissues.
- Resting-phase conidia can also evade macrophage destruction due to the presence of superoxide dismutases, which act as scavengers of reactive oxygen species (ROS).
Dissemination
- During hyphal growth, aerial hyphae invade the endothelial cells of blood vessels within the lungs.
- They initially penetrate the outer vessel walls, then move through endothelial cells into the inner vessel layers.
- Once in the bloodstream, hyphae fragment and circulate, attaching to the luminal surfaces of endothelial cells.
- They then extend into the abluminal areas and continue spreading through the bloodstream to other parts of the body.
- The immune system responds by deploying neutrophils, which adhere to and kill hyphae; however, the extensive fragmentation and spread can overwhelm neutrophil defenses.
- This can result in invasion of pulmonary tissues and vascular structures, leading to thrombosis and tissue necrosis.
- Hematogenous spread may occur, reaching distant organs, including the brain and its tissues.
Clinical manifestation of Aspergillus fumigatus infection
Asthma-like Allergic Bronchopulmonary Aspergillosis (ABPA)
- Occurs when A. fumigatus conidia trigger IgE antibody production, causing an immediate asthmatic reaction.
- In some cases, conidia germinate and hyphae colonize the bronchial tree without invading the lung parenchyma.
- ABPA is characterized by asthma, recurrent chest infiltrates, eosinophilia, and type I (immediate) as well as type III (Arthus) hypersensitivity skin test reactions to Aspergillus antigens.
- Many patients produce sputum containing Aspergillus and have serum precipitins.
- Symptoms include breathing difficulties and the risk of permanent lung scarring.
- Normal individuals exposed to large quantities of conidia can develop extrinsic allergic alveolitis and allergic sinusitis.
Invasive Pulmonary Aspergillosis
- Most common in patients with HIV and low CD4 counts, hematologic malignancies (lymphocytic or myelogenous leukemia, lymphoma), stem cell transplant recipients, and individuals on corticosteroid therapy.
- Follows the inhalation and germination of conidia, leading to pneumonic disease that may or may not disseminate.
- Symptoms include fever, cough, dyspnea, and hemoptysis.
- Hyphae invade both the lumen and walls of blood vessels, resulting in thrombosis, infarction, and necrosis in the lungs.
- The infection can spread to the gastrointestinal tract, kidneys, liver, brain, or other organs, forming abscesses.
- Without rapid treatment, patient deterioration can be rapid and severe.
Endocarditis
- Results from invasive aspergillosis involving the heart muscle.
- Can lead to heart failure, cardiogenic shock, and cardiomyopathy.
Cutaneous Aspergillosis
- Affects patients with surgical wounds or severe skin burns.
- May cause septicemia and wound sepsis.
Laboratory diagnosis of Aspergillus fumigatus
Specimen
- Sputum, bronchial washings, and tracheal aspirates from patients with pulmonary disease.
- Tissue biopsies from patients with disseminated disease.
Direct Microscopy
- Performed using KOH wet mount or calcofluor white stain.
- Examination of sputum samples, bronchoalveolar lavage fluid, or bronchial biopsies reveals non-pigmented, septate hyphae with repeated dichotomous branching.
Cultural Isolation
- Inoculation on basic fungal media such as Sabouraud Dextrose Agar (SDA) yields fast-growing colonies.
- Colony colors may range from white, yellow, yellow-brown, and brown to black or green.
- Microscopic examination shows colonies with characteristic radiating chains of conidia.
Antigen Detection
- Several antigen detection tests can identify Aspergillus from blood, urine, or cerebrospinal fluid (CSF).
- In cases of invasive aspergillosis, serum may show elevated levels of galactomannan antigen.
- Since galactomannan is rapidly cleared from the blood, serial testing twice weekly is recommended for optimal diagnosis.
Serology
- Immunodiffusion tests detect antibodies against Aspergillus species, aiding in the diagnosis of allergic forms, aspergilloma, and invasive aspergillosis.
- Patients with allergic bronchopulmonary aspergillosis often present with high levels of Aspergillus-specific IgE and some IgG precipitins.
Treatment
- Invasive aspergillosis is most effectively treated with voriconazole.
- Resistance to azoles has been reported in some strains; therefore, a combination of voriconazole with Amphotericin B or other antifungal drugs may be used.
- In rare cases, surgical removal of infected tissue is performed, though this carries significant risk as patients with invasive aspergillosis are often critically ill.
- As a preventive strategy, high-risk patients may be administered antifungal agents such as aerosolized liposomal Amphotericin B.
- Early detection is crucial for successful treatment of invasive aspergillosis.
- Allergic forms of aspergillosis are treated with corticosteroids or disodium cromoglycate.
Prevention and Control
- Individuals at risk of allergic infection or invasive aspergillosis should avoid exposure to conidial spores of Aspergillus spp.
- Bone marrow transplant units should be equipped with filtered air-conditioning systems, monitor airborne contamination, limit patient visits, and apply isolation measures to reduce the risk of exposure to Aspergillus conidia and molds.
- Preventive strategies include the use of prophylactic low doses of Amphotericin B or Itraconazole in high-risk individuals.
References
- Jawetz, Melnick, & Adelberg’s Medical Microbiology. (2013). McGraw-Hill Education.
- Prescott, L. M., Harley, J. P., & Klein, D. A. (2002). Microbiology (5th ed.). McGraw-Hill Higher Education.
- Latgé, J. P. (1999). Aspergillus fumigatus and aspergillosis. Clinical Microbiology Reviews, 12(2), 310–350. https://doi.org/10.1128/CMR.12.2.310
- MicroscopeMaster. (n.d.). Aspergillus: Structure, Characteristics, Reproduction. Retrieved from https://www.microscopemaster.com/aspergillus.html
- Mycology Online. (n.d.). Aspergillus fumigatus. The University of Adelaide. Retrieved from https://mycology.adelaide.edu.au
- Klich, M. A. (2002). Identification of Common Aspergillus Species. Centraalbureau voor Schimmelcultures, Utrecht, The Netherlands.
- Sugui, J. A., Kwon-Chung, K. J., Juvvadi, P. R., Latgé, J. P., & Steinbach, W. J. (2014). Aspergillus fumigatus: Pathogenesis, clinical manifestations, and therapy. Clinical Microbiology Reviews, 27(3), 581–620. https://doi.org/10.1128/CMR.00012-14
- Bennett, J. E., Dolin, R., & Blaser, M. J. (Eds.). (2020). Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases (9th ed.). Elsevier.
