A petri dish with cells

Fungi are a unique group of organisms that can live freely in the environment or act as pathogens that cause disease. There are over 1.5 million species of fungi on Earth, but only around 300 are known to cause disease in humans. Fungi have several different methods of causing disease, including infection, toxin production, allergy, and genetic disorders. Understanding why and how fungi can make us sick is key to preventing and treating fungal diseases.

Infection

One of the main ways fungi cause disease is through infection. Fungal infections occur when fungi grow unchecked in or on the body. Different fungi tend to infect different sites based on their natural environment and growth conditions.

For example, the fungus Candida albicans grows well in moist, warm areas. It often lives harmlessly on our skin and mucous membranes. However, if the fungi overgrow, they can cause infections like oral thrush or yeast infections. The warm, moist environments of the mouth allow Candida to thrive if not kept in check by the immune system or competing microbes.

Candida fungi can also cause systemic infections if they get into the bloodstream, often in immunocompromised patients. From the bloodstream, the fungi can disseminate throughout the body and infect organs like the heart, brain, liver, and kidneys. This can lead to dangerous invasive candidiasis with a high mortality rate if untreated.

Toxin Production

Some fungi release toxins that poison animal cells and cause disease symptoms. The types of toxins and diseases depend on the fungus producing them.

For example, Aspergillus fungi release aflatoxins that can contaminate food sources like nuts and grains. Ingestion of aflatoxins can cause severe liver disease and even cancer. The fungi do not directly infect or invade tissue, but their toxins wreak havoc once consumed by animals.

Another example is the black mold Stachybotrys, which produces toxic compounds called mycotoxins. Inhalation of Stachybotrys spores and mycotoxins can cause respiratory distress and bleeding in the lungs. Mycotoxin toxicity rather than invasion is what makes Stachybotrys exposure so dangerous.

Allergic Reactions

Fungi can also cause disease through allergic reactions in susceptible individuals. People can develop allergies to fungal spores or chemicals present on hyphae. When exposed to the allergen, the immune system overreacts, causing inflammation and symptoms like coughing, sneezing, rashes, and asthma attacks.

For example, allergic reactions to mold spores are a common problem for people with asthma or environmental allergies. Breathing in Aspergillus, Penicillium, and other mold spores triggers an overzealous IgE-mediated immune response in the lungs of sensitive individuals. This causes airway inflammation, breathing difficulty, and other signs of an asthma attack.

Allergic fungal sinusitis is another example of fungal allergies causing disease. Mold spores trigger chronic sinus inflammation, causing congestion, facial pain, and headache in allergic patients. The fungi do not invade the sinuses but elicit an allergy-mediated immune reaction.

Genetic Disorders

Some fungal diseases occur because a genetic mutation makes a person more susceptible to fungal infection. Immune cells, skin cells, and other body tissues need to function properly to keep fungi in check. Certain genetic disorders disrupt these processes and provide an opportunity for fungal invasion.

For example, chronic granulomatous disease is a genetic disorder that impairs phagocytes, a type of white blood cell that kills fungi and bacteria. Patients with CGD cannot clear Aspergillus fungi from their lungs and often develop serious fungal pneumonia as a result of their weakened immune response. Their genetic mutation indirectly predisposes them to the fungal disease.

Another condition is Job’s syndrome, a rare genetic immunodeficiency that increases susceptibility to fungal infections like oral and esophageal thrush. The genetic defect prevents proper formation of immune cells and antibodies needed to control Candida fungi. This allows the fungus to proliferate unchecked.

Opportunistic Infections

Many fungal pathogens are opportunistic, meaning they mainly cause infections in immunocompromised individuals. People with HIV/AIDS, cancer, transplants, and other conditions that impair the immune system are susceptible to fungi that normally live harmlessly on the skin and mucous membranes.

For example, Pneumocystis jirovecii is a fungus that almost exclusively causes pneumonia in people with weakened immune systems. Healthy individuals can harbor the fungus with no issues, but immunocompromised patients cannot clear the fungal infection from their lungs once it gains a foothold.

Another example is Cryptococcus neoformans, which frequently infects HIV/AIDS patients but seldom affects healthy people. Without proper T-cell immune responses from the host, Cryptococcus is able to infect the brain and cause deadly meningoencephalitis.

Evasion of Immune Defenses

Fungi have evolved various methods to evade detection and destruction by the immune system. These mechanisms allow fungal cells to avoid being recognized as foreign organisms, preventing an immune response. Without effective immune recognition, fungi can grow unchecked in the body.

For example, the yeast Histoplasma capsulatum disguises itself from immune cells by covering its cell wall with host proteins. This molecular camouflage hides the fungus inside infected macrophages, allowing Histoplasma to spread through the phagocytic cells undetected.

Another stealthy fungus is Pneumocystis, which lacks antigens on its cell wall that would allow it to be identified by the immune system. It essentially hides in plain sight within the host’s lungs as an “invisible” pathogen.

Disruption of Normal Flora

Some fungal diseases occur when there is an imbalance between the fungus and normal microbial flora. The fungus takes advantage of the disrupted environment to overgrow. This is seen with Candida infections after antibiotic treatment.

For example, the vagina hosts a complex mix of bacteria and yeast that keep each other in balance. After taking antibiotics that kill the protective bacteria, Candida yeasts are able to thrive and cause a vaginal yeast infection in the now defenseless environment.

Similar dysbiosis allows oral Candida infections to occur after antibiotic use. The normal oral microbial community regulates Candida, but this control is lost when antibiotics non-specifically destroy the complex flora. Yeast overgrowth leads to painful oral thrush.

Transmission from the Environment

Many fungi are natural inhabitants of the environment and can be transmitted to humans in various ways. Spores from soil, rotting vegetation, and damp areas become aerosolized and infect the lungs when inhaled. Fungi on plant thorns or animal spines can be introduced into the skin through puncture wounds.

For example, Histoplasma fungi thrive in bird and bat droppings. Disturbing contaminated soil aerosolizes Histoplasma spores, which then can deposit in the lungs and cause respiratory infections when inhaled. This fungal disease is acquired directly from the environment.

Another example is Sporothrix fungi, which live in soil, plants, and timber. Gardeners and foresters can acquire Sporothrix infections by getting plant debris contaminated with soil and fungi into cuts and scratches on their hands. The fungus is transmitted from the environment into the wound, causing a localized skin infection.

Fungi as Normal Flora

Many fungi live as harmless normal flora on and inside the human body. They only cause disease when host defenses are compromised or their growth becomes uncontrolled. Otherwise, they peacefully coexist with us.

For example, Malassezia fungi colonize the skin and scalp of most healthy adults. They feed on oils and cellular debris without issue. However, in susceptible individuals, the fungi can overgrow and cause dandruff, seborrheic dermatitis, and folliculitis.

Another fungus that is often normal flora is Candida. Candida species frequently reside in the mouth, GI tract, and vagina without causing problems, but can shift to become pathogenic in the right circumstances.

Summary

Fungi have diverse mechanisms that enable them to shift from harmless to pathogenic in the right circumstances. Disruption of normal flora, evasion of immune defenses, toxin production, opportunistic infection, allergic reactions, genetic disorders, transmission from environmental reservoirs, and overgrowth of normal flora all contribute to fungal diseases. Understanding what allows fungi to cause infections and illness helps medical professionals prevent and treat these harmful diseases. With vigilance and proper treatment, even serious fungal infections can be overcome.

By Gurpret

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