Aspergillus is a genus of several hundred mold species found virtually everywhere on Earth, from soil and decaying vegetation to the air inside homes and hospitals. Most people inhale Aspergillus spores daily without consequence, but in people with weakened immune systems or chronic lung disease, these fungi can cause infections ranging from mild allergic reactions to fatal invasive disease. A handful of species account for the vast majority of human health problems, and understanding which ones matter, and why, is more relevant now than it was a decade ago. The emergence of drug-resistant strains, the recognition that severe viral pneumonias like COVID-19 can open the door to Aspergillus co-infections, and growing concerns about mycotoxin contamination in the food supply have all raised the stakes.
The Species That Cause the Most Trouble
Out of the hundreds of recognized Aspergillus species, fewer than a dozen regularly cause human disease. The ones you are most likely to encounter in a clinical or environmental context fall into a few distinct groups, each with a different profile of risk.
- A. fumigatus: The single most common cause of aspergillosis in humans. It thrives at body temperature and produces tiny spores small enough to reach the deepest parts of the lungs. It is responsible for invasive pulmonary aspergillosis, allergic bronchopulmonary aspergillosis, and chronic lung infections.
- A. flavus: The second most common cause of invasive aspergillosis in many parts of the world, especially in warmer climates. It is also one of the primary producers of aflatoxins, potent carcinogens that contaminate grains and nuts.
- A. niger: Familiar as the black mold sometimes seen on onions and grapes. It is the most frequent cause of fungal ear infections and is also one of the workhorses of industrial biotechnology, producing roughly 99% of the world’s citric acid supply.
- A. terreus: Less common overall but clinically important because it is naturally resistant to amphotericin B, one of the most widely used antifungal drugs, which complicates treatment considerably.
- A. oryzae: Generally considered safe and is the species traditionally used in East Asian food fermentation, including soy sauce, miso, and sake production. It rarely causes disease in humans.
A. fumigatus dominates the clinical picture so thoroughly that when clinicians say “aspergillosis,” they are usually talking about this species. But the others matter in specific contexts, and mistaking one for another can lead to the wrong treatment choice, as the resistance profiles differ sharply between species.
How A. fumigatus Evades the Immune System
Healthy people breathe in Aspergillus spores constantly, and immune cells called macrophages and neutrophils usually destroy them without incident. What makes A. fumigatus dangerous in vulnerable patients is a set of molecular tools that let it dodge and suppress these defenses. The spores are coated in a pigment called DHN-melanin, which gives them their characteristic gray-green color. That melanin is not just cosmetic. It actively interferes with the process immune cells use to kill ingested spores. Specifically, it blocks the acidification of the compartments where macrophages normally digest foreign material, and it disrupts signaling pathways that would otherwise trigger the immune cell to self-destruct the infected compartment.
Mutant strains of A. fumigatus that cannot produce this melanin make white spores and are far less virulent in animal models.
1PubMed Central. Aspergillus fumigatus melanins: interference with the host endocytosis pathway and impact on virulenceBeyond melanin, A. fumigatus deploys a surface protein called hydrophobin that makes its spores essentially invisible to the immune system by masking the molecular patterns that immune cells recognize. It also produces gliotoxin, a toxin that suppresses the ability of neutrophils to generate the reactive oxygen species they need to kill fungi.
2PubMed Central. Gliotoxin is a virulence factor of Aspergillus fumigatus: gliP deletion attenuates virulence in mice immunosuppressed with hydrocortisoneAdd to this a remarkable tolerance for heat, supported by heat-shock proteins and other molecular machinery that let A. fumigatus grow comfortably at human body temperature and even higher, and you have a fungus unusually well-equipped to colonize human tissue.
3PubMed Central. Molecular Insights into Pathogenesis and Infection with Aspergillus FumigatusForms of Aspergillosis
The diseases caused by Aspergillus species are grouped under the umbrella term “aspergillosis,” but the clinical picture varies enormously depending on who gets infected and how their immune system responds. There are three broad categories.
Invasive Pulmonary Aspergillosis
This is the most feared form. The fungus invades lung tissue and can spread to the brain, kidneys, and other organs. It occurs almost exclusively in people with severely compromised immune systems, including those undergoing chemotherapy, organ transplant recipients on immunosuppressive drugs, and people with prolonged neutropenia. Factors like long-term corticosteroid use, preexisting structural lung disease, and viral co-infections all raise the risk.
4PubMed. A multivariable prediction model for invasive pulmonary aspergillosis in immunocompromised patients with acute respiratory failure (IPA-GRRR-OH score)Even with treatment, mortality is high. This is the form that has driven much of the urgent research into new antifungal drugs.
Allergic Bronchopulmonary Aspergillosis
ABPA sits at the opposite end of the spectrum. Here the fungus does not invade tissue; instead, it grows in the airway mucus and triggers an exaggerated allergic response. The immune system overreacts to fungal proteins, causing inflammation, wheezing, and progressive bronchiectasis. It shows up most often in people with asthma or cystic fibrosis.
5PubMed Central. Allergic bronchopulmonary aspergillosis in patients with cystic fibrosisIn cystic fibrosis patients, the thick mucus lining the airways creates an ideal environment for A. fumigatus hyphae to grow, and the resulting allergic cascade drives further lung damage over time.
6PubMed Central. Allergic Bronchopulmonary Aspergillosis (ABPA) in the Era of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) ModulatorsAspergilloma and Chronic Pulmonary Aspergillosis
An aspergilloma is a dense ball of fungal hyphae that forms inside a preexisting cavity in the lung, often left behind by tuberculosis, sarcoidosis, or another disease that previously damaged the lung tissue. It is the most common form of pulmonary aspergillosis overall.
7PubMed. Non-surgical treatment options for pulmonary aspergillomaChronic pulmonary aspergillosis is a broader category that includes aspergillomas but also chronic cavitary disease and a slowly progressive fibrotic form. It tends to develop in people with structural lung damage but without severe immune suppression, and it can smolder for months or years, causing weight loss, coughing, and sometimes life-threatening hemoptysis.
8PubMed Central. Imaging Spectrum in Chronic Pulmonary AspergillosisAspergillosis Beyond the Lungs
While the lungs are the primary battleground, Aspergillus species cause infections elsewhere too. One of the most common is otomycosis, a fungal infection of the ear canal. The acute form affects roughly four in every 1,000 people per year, and A. niger is one of the two most frequently identified culprits alongside Candida albicans.
9PubMed Central. Review of Recurrent Otomycosis and Clotrimazole in Its TreatmentAspergillus species can also cause sinusitis (both allergic and invasive), keratitis after eye trauma or surgery, skin infections at wound sites, and in severely immunocompromised patients, disseminated disease involving the brain and other organs. These extractions highlight a consistent theme: the species are opportunistic. They exploit existing damage or immune gaps rather than attacking healthy tissue on their own.
When Viruses Open the Door
One of the most striking developments in recent years has been the recognition that severe viral pneumonias create a window for Aspergillus to invade the lungs, even in patients who would not normally be considered at high risk for fungal infections. COVID-19-associated pulmonary aspergillosis, or CAPA, was identified early in the pandemic as a dangerous complication in critically ill patients. A multinational study found that among COVID-19 patients admitted to the ICU, the cumulative incidence of CAPA ranged widely depending on the center, from about 1% to as high as 39%. More than half of the patients diagnosed with CAPA died, and in roughly one in six of those deaths, Aspergillus was directly implicated.
10PubMed Central. COVID-19–Associated Pulmonary Aspergillosis, March–August 2020Influenza-associated pulmonary aspergillosis, or IAPA, follows a similar pattern and was recognized even before the pandemic. A diagnosis of aspergillosis can be made in roughly 10 to 20% of patients with severe influenza or COVID-19 when appropriate tests are used, and fatality rates often exceed 50% despite antifungal therapy.
11PubMed. Influenza-associated and COVID-19-associated pulmonary aspergillosis in critically ill patientsComparisons between the two suggest CAPA patients tend to have worse outcomes, with higher rates of complications including secondary bacterial infections, deep vein thrombosis, and heart failure.
12PubMed Central. Clinical Characteristics, Prognosis, and Risk Factors for Mortality in Influenza-Associated Pulmonary Aspergillosis and COVID-19-Associated Pulmonary Aspergillosis: A Multicenter Retrospective StudyAflatoxins and Food Contamination
The health risks of Aspergillus extend well beyond respiratory infections. Two species in particular, A. flavus and A. parasiticus, produce aflatoxins, a group of potent mycotoxins that contaminate staple crops including maize, peanuts, and tree nuts. Aflatoxins are classified as a known human carcinogen and are a well-established cause of liver cancer.
13PubMed Central. Aflatoxins, hepatocellular carcinoma and public healthThe scale of the problem is enormous. Over four billion people worldwide are exposed to dietary aflatoxins, and a systematic review estimated that roughly 17% of liver cancer cases globally are attributable to aflatoxin exposure. The risk is particularly high in regions where hepatitis B is common: in people already carrying the virus, aflatoxin multiplies the cancer risk rather than simply adding to it. Reducing aflatoxin exposure to undetectable levels in high-risk areas could prevent about 23% of liver cancer cases there.
14PubMed Central. Population attributable risk of aflatoxin-related liver cancer: systematic review and meta-analysisAflatoxins are not the only mycotoxin concern. Ochratoxin A, produced by certain Aspergillus and Penicillium species, contaminates cereals, coffee, wine, and dried fruits. It has been linked to kidney damage and kidney tumors in both animals and humans, and dietary intake studies have connected it to endemic kidney disease in some populations.
15PubMed Central. Ochratoxins-food contaminants: impact on human healthThe Growing Problem of Antifungal Resistance
Treating aspergillosis relies on a limited set of antifungal drug classes, and resistance is eroding even that narrow arsenal. The azole drugs, including voriconazole and itraconazole, are the first-line treatment for most forms of aspergillosis. But resistance in A. fumigatus has been climbing, and one of the main drivers is not medical overuse but agricultural fungicide application. Azole fungicides used on crops have molecular structures similar to medical azoles, and A. fumigatus strains that evolve resistance to the agricultural chemicals in the environment are cross-resistant to the drugs used in clinics. Isolates carrying a specific resistance mutation called TR34/L98H have been found to be resistant to all three medical azole drugs and to five agricultural azole fungicides alike.
16PLOS Pathogens. Emergence of Azole-Resistant Aspergillus fumigatus Strains due to Agricultural Azole Use Creates an Increasing Threat to Human HealthA. terreus presents a different resistance problem. It is intrinsically resistant to amphotericin B, a broad-spectrum antifungal that is often the fallback option when azoles fail. Even strains that appear susceptible in laboratory testing can be clinically unresponsive, a phenomenon researchers attribute to drug tolerance rather than outright resistance.
17PubMed Central. Aspergillus terreus and the Interplay with Amphotericin B: from Resistance to Tolerance?Recent laboratory work has shown that A. terreus can shift between resistant and susceptible states through a process called sectorization, where prolonged growth produces morphologically distinct subpopulations with altered drug susceptibility profiles. This adds another layer of unpredictability to treatment decisions.
18PubMed Central. Aspergillus terreus sectorization: a morphological phenomenon shedding light on amphotericin B resistance mechanismDiagnosing Aspergillosis Is Harder Than You Might Expect
One reason aspergillosis mortality remains stubbornly high is that the infection is difficult to diagnose quickly. The gold standard is identifying the fungus in tissue from a biopsy, but that is invasive and often impractical in critically ill patients. Blood cultures are unreliable because Aspergillus rarely circulates in the bloodstream. Clinicians rely instead on a combination of imaging, clinical suspicion, and biomarker tests.
The most widely used biomarker is galactomannan, a sugar molecule shed from the Aspergillus cell wall during active growth. A Cochrane review of the galactomannan blood test found that at the standard cutoff, its sensitivity was about 78% and its specificity about 81%, meaning it catches most cases but misses some and produces a fair number of false positives.
19Cochrane Database of Systematic Reviews. Galactomannan and beta-D-glucan assays for the diagnosis of invasive aspergillosisPerformance improves when the test is run on fluid washed from the lungs rather than blood. In non-neutropenic patients, for example, the lung-wash galactomannan test was about twice as sensitive as the blood version while maintaining similar specificity.
20PubMed Central. Diagnostic Value of Galactomannan Antigen Test in Serum and Bronchoalveolar Lavage Fluid Samples from Patients with Nonneutropenic Invasive Pulmonary AspergillosisThis matters practically: a negative blood test does not rule out the disease, and in patients with strong clinical suspicion, further workup including lung-wash sampling may be warranted.
New Antifungals on the Horizon
Given the resistance challenges, there is active interest in antifungal drugs that work through entirely new mechanisms. Several are in late-stage clinical development. Olorofim, for instance, targets a metabolic pathway in the fungus that existing drugs do not touch, and it has shown activity against azole-resistant Aspergillus strains. Fosmanogepix blocks a different enzyme involved in building the fungal cell wall, and ibrexafungerp targets yet another component of the cell surface.
21PubMed Central. Antifungal pipeline: Is there light at the end of the tunnel?Other drugs in the pipeline include opelconazole, an inhaled azole designed to deliver high local concentrations directly to the lungs while minimizing the systemic side effects of oral azoles, and rezafungin, a long-acting echinocandin that could simplify dosing schedules for seriously ill patients.
22Journal of the Pediatric Infectious Diseases Society. Pipeline of Novel Antifungals for Invasive Fungal Disease in Transplant Recipients: A Pediatric PerspectiveWhether these new agents will reach widespread clinical use quickly enough to offset rising resistance remains an open question, but the pipeline is more promising than it has been in years.
The Industrial Side of Aspergillus
Not all Aspergillus species are enemies. A. oryzae has been used for thousands of years in East Asian food production, and it remains central to the fermentation of soy sauce, miso, and sake. A. niger, despite its role in ear infections, is an industrial powerhouse: it produces virtually all of the world’s citric acid, about 1.4 million tons per year, along with a wide range of enzymes used in food processing, textiles, and biofuel production.
23PubMed. Diversity, Application, and Synthetic Biology of Industrially Important Aspergillus FungiThis duality, the same genus containing both dangerous pathogens and indispensable industrial organisms, makes blanket statements about Aspergillus misleading. The genus is defined by its versatility, and the health risks are concentrated in specific species and specific patient populations.
Climate Change and Shifting Geography
Aspergillus species are sensitive to temperature and humidity, and modeling work suggests that climate change will reshape where they thrive. Under severe warming scenarios, habitat suitability for key Aspergillus species is projected to shift northward. Large parts of Africa, Brazil, and Australia could become less hospitable by 2100, while regions in northern China, Russia, Scandinavia, and Alaska are expected to gain new suitable habitat.
24PubMed Central. Climate change-driven geographical shifts in Aspergillus species and the implications for plant and human healthThese shifts carry implications for both agriculture and human health. Populations in newly suitable regions may encounter higher airborne spore counts and increased crop contamination with mycotoxins without having the clinical infrastructure or surveillance systems to detect the change early.
25PubMed Central. Climate Change and Effects on Molds and MycotoxinsFor food safety regulators in temperate countries that have historically not had to worry much about aflatoxin contamination, the possibility that warmer temperatures will bring toxin-producing Aspergillus into their domestic grain supply represents a genuine emerging risk.
Hospitals and Construction Dust
Indoor environments, particularly hospitals, are a well-known setting for Aspergillus exposure. Construction and renovation work can liberate enormous numbers of spores from dust, soil, and building materials. Hospital outbreaks of invasive aspergillosis have been repeatedly linked to nearby construction projects, especially when barriers and air filtration measures were inadequate. Infection-control risk assessments before and during construction are considered essential to prevent these outbreaks, and guidelines call for measures like sealed barriers, negative air pressure in construction zones, and HEPA filtration.
26Clinical Infectious Diseases. Review of Fungal Outbreaks and Infection Prevention in Healthcare Settings During Construction and RenovationFor people at home, the advice is less dramatic but still worth knowing. Aspergillus thrives in damp environments: bathrooms, basements, air-conditioning systems, and anywhere moisture accumulates without good ventilation. Keeping indoor humidity below about 50%, fixing leaks promptly, and cleaning visible mold are standard recommendations. For immunocompromised individuals, avoiding activities that stir up soil or decaying organic matter, like gardening or composting, is often advised by infectious-disease specialists.