Pathogenesis of Fungal Infection

Pathogenesis of Fungal Infection

Most fungi are obligate aerobes or facultative anaerobes, but none are obligate anaerobes. The natural habitat of most fungi is environment, because all these fungi require a preformed organic source of carbon, hence their constant association with decaying matter. C. albicans is exception and is an important fungus, which is a part of the normal human flora.

Fungi are ubiquitous in nature, i.e., they occur as free-living saprobes, hence determining their role in human infection may sometimes be difficult. The effects of fungi on humans can be grouped in three major ways as follows: (a) colonization and disease, (b) hypersensitive diseases, and (c) diseases caused by mycotoxins or fungal toxins.

Colonization and Disease

Most fungal infections are mild and self-limited. Intact skin is an effective host defense against certain fungi. But if the skin is broken, organisms, the fungi enter through that broken skin and initiate the infection. Fatty acid content, pH, epithelial turnover, and normal bacterial flora of the skin contribute to host resistance against fungi. For example, the mucous mem-brane of the nasopharynx traps inhaled fungal spores.

Cell-mediated immunity is much important in conferring protection against fungi. Suppression of cell-mediated immu-nity can lead to reactivation and dissemination of asymptom-atic fungal infection and to diseases caused by opportunistic fungi. The humoral immunity is mediated by production of IgG and IgM antibody. But their role in protection from fungal disease is uncertain.

Fungal infection that occurs in the immunocompromised hosts is called as opportunistic mycosis. If such conditions are not rapidly diagnosed and immediately managed, they can prove to be life-threatening.

Hypersensitivity Diseases

Humans are continually exposed to air-borne fungal spores and other fungal elements present in the environment. These spores can be antigenic stimulants and depending on individual’s immunological status may induce a state of hypersensitivity by production of immunoglobulins or sensitized lymphocytes. Rhinitis, bronchial asthma, alveolitis, and various forms of atopy are the clinical manifestations of hypersensitive pneumo-nitis. The clinical manifestations of the hypersensitivity disease are seen only in sensitized person, after repeated exposure to the fungus, fungal metabolites, or other cross-reactive materials.

Allergies to the fungal spores are manifested primarily by an asthmatic reaction including rapid bronchial constriction mediated by IgE, eosinophilia, and positive hypersensitivity skin test reaction. These are caused due to immediate hyper-sensitivity reactions of the host to fungal spores.

Diseases Caused by Fungal Toxins

Mycotoxicosis is caused by ingested fungal toxins. Myco-toxicosis caused by eating amanita mushroom is the best exam-ple of mycotoxicosis. This group of fungi produces five toxins. Of these, amanitine and phalloidin are the two most potent hep-atotoxins. The toxicity of amanitine is due to its ability to inhibit cellular RNA polymerase, which prevents mRNA synthesis.

Aflatoxin is another fungal toxin produced by Aspergillusflavus that causes disease in humans. Aflatoxin-B causes amutation in the P53 tumor-suppressor gene, resulting in a loss of P53 protein, thereby in a resultant loss of growth control in the hepatocytes. Hence, it causes damage to liver, and it induces tumor in liver in animals and is associated with hepatic carci-nomas in humans.

Claviceps purpurea is a mold that infects brain and producesalkaloids, such as ergotamine and lysergic acid diethyl amide. These compounds cause serious vascular and neurological effects.

Yellow rice toxicosis in Japan and elementary toxic aleu-kia in the former Soviet Union are the examples of other mycotoxicoses.

The transmission and habitat of some important fungi in India are described in Table 71-2.