MicrobiologyBytes: Microbiology Notes: Mycology Updated: April 18, 2007 Search

Environmental Mycology

Introduction

Fungi are extremely important in the biosphere. They have both very positive and very negative impacts on us. For instance, the metabolic by-products of yeast metabolism have been exploited by humans for bread making and alcohol brewing. Both processes considerably enhance the value to us of the original substrate whilst contributing little to its nutritional status!

Fungi are able to produce many different types of metabolite in commercial fermentation processes that are much more efficient than chemical synthesis. For example enzymes that are used in the food industry (e.g. amylase, rennin), other enzymes (e.g. cellulases, catalase), acids (e.g. lactic, citric), and several other products. They also can be used to produce novel families of antibiotics (e.g. Penicillins and Cephalosporins), and immuno-suppressants (cyclosporins) which can then be improved on by pharmaceutical industries.

Fungi can also be used to produce large quantities of protein. Yeasts were used to make single cell protein in the 1960s and fungal protein extracted from Fusarium graminearum is a useful meat alternative known as Quorn.

MicrobiologyBytes: Fungi

Fungi as symbionts

Fungi can also enter into close associations with other microbes and with higher plants and animals. These beneficial associations are termed symbioses.

Fungus-root symbioses

These associations are common on plant roots, and are termed termed mycorrhizae. Their presence enhances plant root plant performance and nutrient uptake. The fungal association can be external to or within the root tissue. These associations are seen on the roots of forest tress, shrubs and herbaceous species like grasses.

Fungus leaf symbioses

Fungi can occur within leaves or stems as symptomless infections. These fungi are called endophytes. They live almost all their life cycle within the host, grow very slowly whilst the organ they colonize is alive, and do not cause any signs of infection. They may protect their host from animal grazing or other pathogenic fungal infection by the production of metabolites. However, these products can have dramatic effects on herbivorous animals, causing symptoms of fungal toxicosis similar to St. Anthony’s Fire.

Fungus-alga symbioses

Some fungi can form slow-growing, very intimate associations with algal species. These associations are called Lichens. They are adapted to occupy extreme or marginal environments, like bare rock faces, walls and house roofs. They are highly sensitive to pollution because they are under quite extreme environmental pressure, and their presence in an environment has become a useful indicator of a lack of urban and industrial pollution.

Fungus insect symbioses

Fungi can also associate with insect species. Some species of ants culture specific fungi on plant remains they bring to their nests. The ants can then browse on the fungal mycelium that develop on the chewed leaves. Termites have symbiotic fungi within their guts, which, in association with a consortium of other microbes, help the termite digest its woody gut contents.

Decomposers, bio-deterioration and bio-redemption

The processes that fungi perform with their degradative enzymes are essential to the terrestrial biosphere. Fungi are the main agents of decay of cellulose wastes produced by plants. They decompose this material to carbon dioxide, water and fungal biomass. The same extracellular enzymes that are important in the saprophytic colonization of substrates in the biosphere can cause significant economic losses when they utilize paper, cloth, leather and hydrocarbons as substrates. They can also can cause degradative change in other materials because of their ability to produce acid as they grow, for instance glass and metal can be etched by extracellular acid production.

However, fungal enzymes can be used on other, man-made substrates to provide biological cleanup. Such activity is termed bioremediation, and land contaminated with a number of hydrocarbons, and other toxic materials like PCBs can be actively bioremediated by the addition of fungi.

Plant disease

Fungi are capable of attacking all plant species, causing serious damage and in some circumstances even death. In crop production over half of potential crop yield is lost to plant pathogens, most of it to fungal disease. In storage, up to one third of the harvested product can be lost to post-harvest disease, again mostly due to the activities of fungi. Use of fungicides can reduce both pre- and post-harvest disease, and plant breeding programmes can introduce disease resistant strains of crop plant. Post-harvest losses can be reduced by storage of products at low temperatures and low moisture levels.

Human and animal disease

Although plants are susceptible to fungal pathogens, animals and humans are far less susceptible to fungal infections. There are many barriers to fungal infection in animals and man. Skin is a physical barrier to infection. It also secretes fungistatic fatty acids and desquamates (skin cells desiccate as they die and fall off shedding fungal infections with them). Mucous membranes and their secretions are also effective barriers, and the human and animal immune system which includes cell mediated immunity and humoral immunity, is highly effective against fungi.

Furthermore, within the body the acidity of the upper GI tract renders the habitat untenable to fungi. To some extent there is also a resident microflora on all surfaces of the body which acts to occupy the niche through competition and antibiosis.

Reasons for fungal infections

There are usually a number of reasons for fungal infections. Any condition that suppresses the immune system will increase the risk of fungal infections. Conditions such as chronic stress, pregnancy, reticular endothelial illness, cancer, diabetes, chemotherapy, immuno-suppressants, use of antibiotics, catheters, radiation, burns and AIDS.

Epidemiology

There are three main sources of infection. Human to human, animal to animal or animal to human or vice versa. However, some infections are occupation related and are from environmental sources. There are superficial, subcutaneous and systemic infections.

Superficial infections:

These occur when fungi colonize dead, keratinous tissues like hair. The fungus is entirely extracellular and merely grows on the substrate, avoiding the hosts immune system.

The fungi that can grow on skin and mucus membranes are described as zoophilic or anthropophilic species with close saprophytic relatives. These pathogenic species probably originated from the free living species, but now are reproductively isolated. Many different species of fungus can invade the same tissues, and the same fungus can invade many different tissues, feet, hair, beard etc. These are self limiting infections of the upper epidermis, and fungi that infect this superficial layer of epithelium are often called dermatophytes. The dermatophytes are well adapted for this niche and are not opportunists in that they can infect non-immunocompromised individuals. They can all use keratin as a nutrient source, and belong to forty species in three genera of fungi, Trichophyton, Epidermophyton and Microsporium. They are undergoing re-classification as links have been found to Ascosporic phases, so there are several names for the same fungus at the moment.

Table 1: Some examples of superficial fungal infections

Fungal species:

Disease:

Arthroderma spp. (syn Tinea pedis, capitus, barbae etc)

Athletes foot, Ring worm etc

Microsporium canis

Ringworm of pets

Pityrosporon orbiculare

Can invade the stratum corneum and cause Pityriasis versicolour

Phaeoanellomyces (Cladosporium) werneckii

Can invade the stratum corneum and cause Tinea nigra

Piedriai hortai

Black Piedra

Trichosporon beiglii

White Piedra, infection of the hair follicle resulting in white nodules attached to the hair shaft

Malassezia furfur

Malassezia folliculitus

Candida albicans

Thrush

Subcutaneous Mycoses:

Sporotrichiosis. Can cause local lesions on hands and fingers, causing a disease known as Rose Growers disease. However this fungus can also cause deeper infections (see later).

Maduramycosis. This infection is from fungal spores entering a deep injury to a bony structure like a foot. The infection causes deep infections, characterized by the formation of sinuses that drain from an abcess-like infection up to the surface of the foot. There can be bone and muscle involvement at the later stages of disease, which leads to the deformation of the limb. Several different Deuteromycetes have been identified as being able to cause this disease, including Phialophora spp, Acremonium sp. Leptosphaera spp. and Madurella spp. The infection does not respond well to anti-fungals and usually it needs surgery or amputation.

Systemic mycoses:

In Table 1 is a summary of symptoms, in Table 2 is a summary of the different systemic mycoses, with their causal fungal species, their colonial habit at environmental and 37°C, and a few details of the disease they cause. In Fig. 1 there are some sketches of some of the common species from either environmental or tissue samples

Table 2. The different tissue responses to fungal invasion:

Chronic inflammation:

Zygomycosis:

Granulomatous inflammation

Candidiasis

Coccidiomycosis

Cryptococcus infection

Histoplasmosis

Blastomycosis

Acute suppurative infections

Mycetoma

Candidiasis

Sporotrichosis

Histoplasmosis

Zygomycosis

Aspergillosis

 

 

Figure 1. Some fungi that can cause infections of man:

Fungus:

Culture:

Disease, Route of entry and Histopathology:

Aspergillus spp.

Ascomycete

Ubiquitous member of normal air spora

White mycelium that produces green, yellow or fawn columns of spores

Aspergillosis.

Inhalation. Septate hyphae with dichotomous branching within pulmonary cavity of immunocompromised individuals.

Blastomyces spp.

Ascomycete

Colonizes only bat and bird dung, tends to be tropical/sub-tropical in its distribution

Large (8-14 µm), thick walled yeast cells with wide (4-5 µm) pores between bud and parent at 37°C. At lower temp mycelium produces hyphae with conidiophores at 90° angle

Blastomycosis.

Inhalation. Infects lungs, lymphatics, spleen and eventually bone

Candida spp.

Ascomycete

Skin saprophyte

Spherical chlamydospores 8-12 µm in diameter

Can produce blastospores within body fluids under suitable conditions

Histoplasma capsulatum

Ascomycete

Large (8-14 µm) macroconidia produced at 30°C

Histoplasmosis

Inhalation. Infects pulmonary system followed by spread to lymphatics. Fungaemia can occur (yeasts within macrophages or polymorphonuclear leukocytes)

Cryptococcus neoformans

Basidiomycete

Only found in pigeon droppings

Spherical cells (4-20 µm) formed at 37°C. Tends to form a capsule of polysaccharide.

Inhalation.

Capsule often larger in lung tissues

Paraccoccidiodes brasiliensis

Ascomycete

Americas from Mexico to Argentina

Spherical or elliptical cells with single or multiple buds

Paracoccidiomycosis affects lungs but later invades lymph nodes, adrenals. Long latency period (30 plus years has been recorded)

Pneumocystis carinii

Ascomycete

Ubquitous in air spora

Yeast like cell

PcP pneumonia. Grows within lungs to produce pneumonia once CD4 T cells are depleted

Mucor spp. Rhizopus spp. Absidia spp.

Phycomycetes spp.

Abundant fluffy growth with sporangia

Inhalation, wound invasion Mucormycosis, zygomycosis, phycomycosis

Mycelium grows within tissue, broad hyphae with few cross walls.

Coccidiodes immitus

Phycomycete

Normally only found in desert soils

Mycelium produces arthrospores in culture

Inhalation. Grows from inhalation in lung, forms multinucleate sporangia in deep tissue. Rarely fatal.

 

It is often very difficult to get a differential diagnosis of fungal infections because sputum and tissue samples are all very difficult to isolate mycelium from. Antigen detection, antibody detection and fluorescent antibody tagging have all been used with some success.

Pathogenicity factors

Much is still unknown about the pathogenicity factors that make for a successful animal and human fungal pathogen. An ability to grow at 37°C is obviously a prerequisite, but other than that little is known. Another feature which allows fungi to be successful pathogens may be that of dimorphism. Some pathogens are characterized by a temperature controlled change in morphology, that below 33°C the mycelial form exists, but above 33°C the yeast form exists. Control of this switch seems to be mediated by cAMP, which is 5-fold higher in the mycelium, but the precise control mechanism is unknown. There are a number of other factors that appear to be important:

Adherence:

This is affected by the hydrophobicity of the fungal cell wall which is under environmental and genetic control. At neutral pH adherence is better, and fungal surface adhesins aid in binding to host membranes. This feature is important in Candidiasis

Colonization:

Entry can be via the pulmonary route where spores will germinate and colonize the lung tissue as hyphae. Enzymes may be involved in colonization, but as the tissue is bathed in a nutrient fluid most enzymes are likely to be under end product inhibition.

Avoidance of host defences:

There is some evidence that some fungi are able to change their antigenic surface structure and evade host immune systems.

Extracellular fungal products:

Extracellular enzymes, particularly the secreted aspartyl proteinases, seem to be correlated with virulence of fungal pathogens. Extracellular toxins from fungi can also contribute to the clinical picture of fungal disease. Aspergillus fumigatus produces Aspergillus haemolysin toxin. This is a polypeptide, which resembles bacterial endotoxin-LPS like protein complex .This toxin causes haemolysis. Aspergillus fumigatus also produces Fumitremoragen A & B which has steroidal structure and causes tremors and death. Candida albicans produces canditoxin which is also peptidic, and toxic to lymphocytes.

Treatments

Fungi like animals and man are eukaryotic, and thus any cytotoxic drugs that are effective against fungi are going to have toxic side effects for the host.

Treatments for fungal infections include the polyenes, including amphotericin B and nystatin, and the azoles including the imidazoles(e.g. ketokonazole) and the triazoles (itraconazole and fluconazole). Compounds with higher cytotoxicity can be used for superficial lesions (e.g. griseofulvin). However, increasingly there are reports of resistance appearing which seem to be based on three phenomena. The best data set is from Candida, where there are several factors that may contribute to emergence of resistance including the frequency and dosage regime or an intermittent dosage of anti-fungal. Furthermore, a number of effects have been seen in the pathogenic strains. There is a varying degree of intrinsic resistance of the endogenous strains, and with an intermittent drug dosage or one below MIC there is a replacement of the endogenous strain with more resistant strains.

The molecular mechanisms of antifungal resistance can include a change in sterol components of plasma membrane, a genetic change including point mutations etc, and alterations in other enzymes in ergosterol biosynthetic pathways.

Fungal toxicosis

Accidental or deliberate consumption of wild fungi or fungally contaminated food can lead to poisoning or toxicosis of the consumer because some fungi naturally contain toxic metabolites called mycotoxins. Deliberate toxicosis can arise from consumption of mushrooms and toadstools that are known to naturally contain hallucinatory drugs like Psilocibins, which lead to euphoric states followed by extreme gastro-intestinal distress. Accidental consumption of mis-identified fungal fruit bodies can lead to mushroom poisoning from fungal toxins that is lethal, causing total liver failure between 8-10 hours. Consumption of food accidentally contaminated by fungal metabolites also leads to human and animal death. For instance, rye flour contaminated by the ergots of the fungus Claviceps pupurea leads to the symptoms of St. Anthony’s Fire, where peripheral nerve damage is caused by the presence of Ergometrine in the fungal tissue. This can be followed by gangrene of the limbs and death. Detection of fungal mycotoxins like Ochratoxin in apple juice and Aflatoxin in peanuts have also caused problems for food producers and consumers and forced improvements in product processing.

 


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