REVIEW OF MEDICAL MYCOLOGY

Fungus: Fungus is chlorophil free, nonphotosynthetic eukaryotic organism. Mycology: It is the branch of microbiology which deals with fungus. Mycosis: Disease caused by fungus.

Over 100,000 fungal species identified. Only about 200 are human or animal pathogens. Most human fungal infections are nosocomial and/or occur in immunocompromised individuals (opportunistic infections). Fungal diseases in plants cause over 1 billion dollars/year in losses.

Eukaryotic microorganisms Cell wall : Carbohydrate 80% (chitin, chitosan, Betaglucan, cellulose and mannan), Protein - 10% and Glycoprotein - 10% Chittin: Special Carbohydrate composed of long chain N-acetylglucosamine Cell membrane: Sterol: ergosterol, zymosterol, lynosterol Cytoplasm: mitochondria, other usual organelles. Nucleus: contain nuclear membrane and nucleoli. Capsule: Non essential, extra layer of poly saccharide outide the cell wall.

Fungi are heterotrophic organisms, lack of chlorophyll (plant; autotrophic) saprophytes, parasites and mutualists (symbionts i.e. lichen ) Store their food as glycogen Both sexual and asexual spore may be produced To synthesize lysine by the -amino adipic acid pathway (AAA-pathway) Bacteria and plant synthesize by diaminopimelic acid pathway (DAP-pathway)

Classification
On the basis of morphology
Yeast Mould Yeast like Dimorphic Ascomycotina Zygomycotina Basidiomycotina Deutormycotina Superficial Cutaneous Sub-cutaneous Deep

On the basis of reproduction

On the basis of disease production (Phylogenetic)

Fungi- Morphological Classification

Moulds Yeasts & Yeast like Dimorphic

Aspergillus
A. fumigatus
Mucorales (zygomycetes) Mucor spp. Rhizopus spp. Dermatophytes

phases Cryptococcus Moulds 250C Yeasts/other 0 /forms(37 C)

C. neoformans C. gattii C. albicans

Candida

Histoplasma capsulatum Coccidioides immitis Blastomyces dermatitidis Sporothrix schenkii

Malassezia

M. furfur M. globosa

Morphological classification
Based on size and shape of fungus

Yeast
Unicellular, spherical or elliptical structure which reproduce by asexual budding except a few that divides by binary fission. Size 8-15 x 3-5 m They grow at 35-37 0C, body temp. eg.Cryptococcus neoformans

Colonial morphology OF

Yeast...

Yeast like
Yeast with budd in chain. Budd when not separate form long chain, look like hyphae called pseudohyphae. Eg. Candida species

Mould
Multicellular, filamentous, cylindrical, elongated
structure with branching tubules called hyphae

Diameter 4-20 m They grow at 22-25 0C, Room temp. Eg. Dermatophytes.

Colonial morphology of

Mold...

Hyphae Structure
Nuclei Cell wall Cytoplasm

Cross wall Nuclei

Cell wall Cytoplasm

Hyphae With Cross Walls

Hyphae Without Cross Walls

Dimorphic:
Fungus which grow as yeast at 37C and as mould at 25 C (thermally

dimorphic fungi).
eg.Histoplasma capsulatum Blastomyces dermatitidis.

Environment/Routine culture media (SDA) 25-300C ---Mold form

Sporothrix schenckii

Tissue/Enriched media (BHI) 35-370C---Yeast form

Classification of Fungi
Four major division of fungi base on the type of sexual spores (ascospore, basidiospore, zygospore, oosore) plus another group, which have no know sexual state.
Ascomycota Basidiomycota Zygomycota Chytridiomycota Deuteromycota (Imperfect fungi)

Division: Ascomycota
Common name: Sac fungi Sexual reproduction: ascospore Asexual reproduction: conidia, arthospore, budding septate hyphae Aspergillus sp. Penicillium sp.,

Life cycle of Ascomycetes

Division: Basidiomycota
Common name: Club fungi, mushroom Sexual reproduction: basidiospore Asexual reproduction:budding septate hyphae, clamp connection Amanita phalloides Mushroom:
Amanita muscaria

Division: Zygomycota
Common name: Bread molds Sexual reproduction: Zygospore Asexual reproduction: Sporangiospore, sporangium Rhizopus sp., Mucor sp., Asidia sp.

Life cycle of Rhizopus stolonifer

Division: Chytidiomycota
Common name: Water molds Sexual reproduction: Oospore Asexual reproduction: Zoospore, zoosporangium, have flagella aseptate hyphae Phythium insidiosum

Deuteromycota
Common name: Imperfect fungi have no known sexual state in life cycle Asexual reproduction : conidia (blastic, thallic) septate hyphae Human pathogenic fungi: dermatophytes, dimorphic fungi

Clinical classification
Based on the anatomical sites involved 1.Superficial fungal agents: Infects the outer most layer ie Stratum corneum of the epidermis. Eg.
Superficial fungal agents Malassezia furfur Piedraia hortae Trichosporon beigelii Superficial mycoses Ptyriasis versicolor Black piedra White piedra

2.Cutaneous fungal agents:

Lesion in the dermis but manifest by whole thickness of skin. Eg. Cutaneous fungal agents Cutaneous mycoses Dermatophytes Dermatophytosis / Ring worm

3.Subcutaneous fungal agents: Infect subcutaneous tissue. Eg.

Subcutaneous fungal agents Sporothrix schenkii Rhinisporidium seeberi Mycetoma Subcutaneous mycoses Sporotrichosis Rhinisporidiosis Madurella mycetomatis

4.Deep fungal agents

a)Primary fungal agents: Cause systemic infection in healthy individual. Eg. Primary fungal agents Primary mycoses Histoplasma capsulatum Histoplasmosis Blastomyces dermatitidis Blastomycosis Coccidioides imitis Coccidioidomycosis b)Opportunistic fungal agent: Cause systemic infection in immunocompromised individual. Eg. Oppurtunistic fungal agents Oppurtunistic mycoses Cryptococcus neoformans Cryptococcosis Candida albicans Candidiasis Aspergillus fumigatus Asergillosis

Contribution of fungus:
Beneficial effects: 1.They reside in nature and are essential in breaking
down and recycling organic matter. 2.Enhance our quality of life by contributing production of food and spirit

3.Used in medicine: Antibiotics, Adrenergic alkaloids, Immunosuppressive agents (cyclosporin).

4.Eaten as Mushroom.

Harmful effects: 1.Fungi exert their greatest economic impact. Agricultural industry sustains huge crop losses as a result of fungal diseases of plants every year. 2.Fungi as Parasites Cause serious plant and animal diseases and a few cause diseases in humans Human Diseases Athletes footz Candida albicansoral thrush

Athletes footz

oral thrush

Reproduction of fungus:
1.Asexual reproduction: Producing spore or conodia usually by budding and binary fission. 2.Sexual reproduction: 1+1 Haploid cell = Diploid cellMitosis Meiosis - Haploid cell. 3. Parasexual reproduction: Meiosis in one anatomical region but budding in other site in same strain. Exchange of gene. Give rise to new genetic form.

Types of diseases/disorders
1. Mycotoxicosis - caused by ingested toxins
2. Allergic - Asthma, allergic bronchopulmonary disease, IgE and or IgG mediated 3. Colonization and invasion -Superficial and cutaneous -Subcutaneous -Deep seated, disseminated -Opportunistic mycoses -True (endemic) mycoses

Mycotoxicoses
Fungi can generate substance with direct toxicity for humans and animals. Such toxins are secondary metabolites. They are synthesized and secreted directly in the environment. They include a variety of mycotoxins elaborated by Mushrooms.

Exposure to these toxins after their ingestion result in a disease termed as mycetismus. The severity of the disease depends on the amount and type of mycotoxin ingestion. Heating of mycotoxins has little effects on reducing the toxicity. Eg.

Amatoxins and Phallotoxins: They derived from poisonous mushroom Amanita which may yield several toxins including phalloidin, phalloin and alpha bata and gamma amanitin. The liver is the target organ for both families of toxins. Amanitin prevent messenger RNA synthesis by inhibiting cellular RNA polymerase enzyme The treatment of mushroom poisoning is largely supportive, as specific antidots are not available.

Aflatoxins: Some fungi elaborate a variety of mutagens and carcinogens. The most potent and best characterized example is Aflatoxin. There are eight variety of aflatoxins produced by certain strains of Aspergillus flavus and other mould. Aflatoxin is the most potent liver carcinogen in humans and also induces many other molecular changes.

Laboratory diagnosis of fungal infection

Principle: It is based on demonstration of fungal agents by direct microscopic examination. Isolation and identification by culture. Serological tests and nucleic acid based techniques are also helpful. Steps: Collection of specimen Skin scraping Nail cutting Hair plucking

Microscopic examination: Wet preparation after partial digestion of keratin tissue by 10-20% koh solution. Gram stained smear: For yeast Giemsa stain: For Histoplasma capsulatum. India ink preparation: For cryptococcus neoformans. Calcofluor stain and Methenamine silver stain is also helpful in microscopic diagnosis of fungi in tissue.

Culture: Media: Sabourrauds dextrose agar media Temparature: 25-37 C Time: 2-3 weeks Serological tests: Detection of fungal Ag or Ab by ELISA, RIA, LA.

Nucleic acid beased technique: DNA Probe can be used to identify fungi growing in culture at a much earlier stage.