Fungi constitute a large, diverse group of heterotrophic organisms. They are eukaryotic and can vary considerably in size and shape. The have two main groups the moulds and the yeasts. The moulds are filamentous or mycelial fungi and are composed of branched filaments or hyphae.

They reproduce by means of spores produced by asexual cell division or sexual reproduction with different types of spores produced dependent on growth conditions. The yeasts are predominantly oval and unicellular. They reproduce by the asexual process of budding.

Some fungi are said to be dimorphic and can grow in the mycelial or yeast phase, depending on growth conditions, many of these fungi are pathogenic to man.

Fungi have several disadvantageous roles in human health where they cause disease. Less than 1% of fungi are know to cause diseases, or mycoses. Most are dimorphic but there are also a number of pathogenic yeasts. Dimorphic fungi usually assume the mould form when growing and the yeast form when causing infection. Some fungi are able to establish infection in all exposed individuals, others are opportunists which can ordinarily only cause disease in the compromised host. In some mycoses the form and the severity of the infection depend on the degree of exposure to the fungus, the site and method of entry and the level of immunocompetence of the host. Most infections are caused by environmental moulds but also yeasts that are commensals of man and can cause endogenous infections in the compromised host. Pneumocystis carinii is the most common cause of death amongst AIDS patients. Fungal infections of man can be divided into three categories. The first are the superficial mycoses. These are diseases of the skin, hair, nails and the mucous membranes and are the most common fungal infections. There are secondly subcutaneous mycoses these are the mycoses of the subcutaneous tissues and bone, they show slow, localised spread. The final category are the systemic mycoses, these are deep fungal infections and generally result from the inhalation of spores.

The dermatophytes cause superficial mycoses such as ringworm and athletes foot, they grow by parasitism. The anthropophilic species are characteristically associated with humans. T. interdigitale growing between the toes causes athletes foot. These fungi live on the skin just above where the keratin is deposited. They rarely invade the living epithelium but cause irritation due to their antigenicity. The scratching that they cause can lead to further spread of infection. If the human has a mild wound keratinisation of the skin is increased, this favours the fungi by increasing the substrate available for metabolism. Alternatively an acute inflammatory response ceases keratinisation and resolves the infection. Dermatophyte infections are promoted by the high humidity caused by tight clothing and mild abrasion.

A key subcutaneous mycoses is caused by the commensal Candida albicans. This is a yeast which can change to a hyphal form. It is a very common commensal of humans in the mucous membranes of the mouth, gut and female vagina. It causes no harm and its population is kept in check by a combination of the bodies natural defences and bacterial competition. Although it can be a problem to human health if the balance is disturbed. This allows proliferation of the yeast in the mucosa causing local irritation that can progress to systemic disease. C. albicans is known to cause ‘thrush’, producing white speckling hence the name. This is common in newborn babies where it grows in their mouth and throat, when delivered through an infected birth canal. The fungus is able to proliferate on the newborn before the microbial population has developed to control it. C. albicans also causes vulvovaginitis in pregnancy or women using oral contraceptives. The contraceptive gives a hormonal disposition to the condition.

A small number of fungi infect through the lungs because there airborne spores are small enough to reach the alveoli. These fungi cause systemic infections. Systemic mycoses include coccidioidomycosis caused by a dimorphic fungi that infects the lungs and aspergillosis caused by a mycelial fungi that can also infect the lungs.

However the products of fungal metabolism can also have adverse effect on human health. Mycotoxins, are a diverse range of compounds from different precursors and pathways, all toxic to humans. The mycotoxins include phallotoxin, a toadstool toxin and potent human carcinogen which has been show to cause liver cancer. Some mycotoxins that can produce intoxication and hallucination.

There are several affects on human health caused by mushroom toxins. Mushrooms are the fruiting body of the fungi and known to cause mycetismus, mushroom poisoning. Protoplasmic poisons are found in the Amanita species, they are cyclic peptides that mobilise hepatic glucose. In man they cause blood pressure to fall, a decrease in sugar and sodium chloride content of the blood, residual blood urea to increases, potassium deficiency and leukocytosis. If the patient survives this first stage a hepatomegally, or enlargement of the liver occurs, alongside cramps, dilation of the pupils, albuminia, haemoglobinuria and oligouria. The ultimate fate is death, usually caused by acute hepatic necrosis. Some mushrooms also contain compounds with a neurological effect. Inocybe contains muscarine which exerts a specific peripheral parasympathetic activity, due to its effect on the post ganglionic parasympathetic effector sites. Symptoms of poisoning appear fifteen to thirty minutes after ingestion causing irregular pulse, constricted pupils and asthmatic breathing. Some mushroom toxins cause hallucinations. ‘Pilzatropine’ is an unidentified compound found in A. muscaria. That produces symptoms on the CNS similar to those induced by the drug atropine. It induces restlessness, confusion, disrupts vision and causes muscle spasms. Psilocybin and psilocin, present in Russula, have similar psychtrophic or hallucinogenic properties. Some species of fungi also contain tetraethylthiuram (TETD). This has no adverse effect on human health, however when consumed with alcohol, TETD ethanol reaction occurs leading to hyperventilation and tachycardia.

Fungi need not only be considered for their pathogenic or adverse effects on human health. They also have advantages in their role of antibiotic production. An antibiotic is a diffusable secondary metabolite. The best known fungal produced antibiotics are the penicillins and cephalosporins. All of these are used clinically to benefit human health Penicillin was discovered by Alexander Flemming as a metabolite of penicillium notatum. Penicillin is most active against gram positive bacteria, preventing the cross linking of peptides during the synthesis of peptidoglycan in bacterial cell walls. This means that the cells can not grow properly and are susceptible to cell lysis. Penicillin is now produced commercially from the high yielding strain P. chryysogenum. These strains have been mutated to produce thirty times as much antibiotic as the wild type. Chemical additions of specific acyl groups to produce a range of semi synthetic penicillin’s, which have different synthetic properties. Oxacillin is resistant to some bacterial b lactamases, enzymes that cleave the ring of penicillin G and inactivate the antibiotics, ampicillin has activity against some gram negative bacteria and penicillin V has enhanced resistance to degradation by stomach acids. Despite their advantages to human health in the treatment of disease penicillin’s can cause an allergic reaction in some individuals. These problems are being addressed by another group of antibiotics cephalosporins, a product of the fungus C. acremonium. The cephalosporins are close cousins of the penicillin’s. It has an additional carbon which allows additional substitutions. They have been associated with hypothrombinaemia and bleeding. Cephalosporins have an advantage over penicillin’s as they are stable to b lactamases.

There are other fungal products which also have a therapeutic effect. Ergot is an example with toxic characteristics which given at proper levels can be a pharmaceutical. Ergot is the resistant stage of Claviceps purpurea it contains five or more optically active isomers. The L isomers are active in inducing uterine contractions, controlling bleeding and alleviate localised vascular disorders.

Genetic engineering of fungi has also reaped benefits for human health. S. cerevisiae has been used to produce pharmaceuticals. The process occurs by the introduction of foreign, heterologous, genes. The yeast has been used to produce genetically modified hepatis B vaccine, produced by engineered genes for a virus coat antigen. Many other proteins have been produced experimentally, cellulases, amylases, interferon, epidermal growth factor and b endomorphins all of which are useful to human health. Fungi have internal enzymes which can be exploited in bioconversion in the production of pharmaceuticals. They can perform dehydrogenations and hydroxylations on a compound to produce a new one.

In conclusion fungi can play many important roles in human health. These roles can be adverse in causing disease or mycoses. This can be by the actual fungi reproducing in the human host, from fungal toxins and fungal fruiting bodies. Although some fungi are truly pathogenic, most are opportunistic and are more prevalent in the immunocompromised host, a particular problem in the AIDS population and also in transplant patients. However many antifungal treatments are now available to treat fungal infection, yet few are specific enough to treat fungi and not man as both are eukaryotic. Therefore if the fungi can be controlled by man they can be considered for the benefits they give to human health. That is the production of antibiotics particularly penicillin and more recently cephalosporin. Yeasts have also been used to genetically engineer other hormones and drugs to benefit health, including interferon and hepatitis vaccine. Therefore if the pathogenic effects of fungi can be controlled their role as aids to health prevail.

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