BASIC BASIC MYCOLOGYMYCOLOGYR.Varidianto Yudo T., drR.Varidianto Yudo T., dr

STRUCTURE & GROWTHSTRUCTURE & GROWTH

Because fungi (yeasts and molds) Because fungi (yeasts and molds) are are eukaryoticeukaryotic organisms whereas organisms whereas bacteria are prokaryotic, they differ bacteria are prokaryotic, they differ in several fundamental respects.in several fundamental respects.

Two fungal cell structures are important Two fungal cell structures are important medically :medically :

(1) The fungal cell wall consists primarily of (1) The fungal cell wall consists primarily of chitinchitin* (not peptidoglycan as in bacteria); thus, * (not peptidoglycan as in bacteria); thus, fungi are insensitive to antibiotics, such as fungi are insensitive to antibiotics, such as penicillin, that inhibit peptidoglycan synthesis.penicillin, that inhibit peptidoglycan synthesis.

(2) The fungal cell membrane contains (2) The fungal cell membrane contains ergosterolergosterol and and zymosterolzymosterol, in contrast to , in contrast to human cell membranes, which contain human cell membranes, which contain cholesterol. The selective action of cholesterol. The selective action of amphotericin B on fungi is based on this amphotericin B on fungi is based on this difference in membrane sterols.difference in membrane sterols.

There are 2 types of fungi: There are 2 types of fungi: YEASTSYEASTS and and MOLDSMOLDS. .

YEASTSYEASTS grow as single cells that grow as single cells that reproduce by asexual budding. reproduce by asexual budding.

MOLDSMOLDS grow as long filaments grow as long filaments ((hyphaehyphae) and form a mat ) and form a mat ((myceliummycelium). ).

Some hyphae form transverse walls Some hyphae form transverse walls ((septate hyphaeseptate hyphae), whereas others do ), whereas others do not (not (nonseptate hyphaenonseptate hyphae). ).

Hypha, septate, or nonseptate.

Mycelium: web of branched hyphae.

Yeast form, budding (diameter of individual cell 3–5 lm).

Bud and birth scars in a yeast cell. The scanningelectron micrograph shows a bud scar (BS) and a birth

scar (BirS) onthe surface of a Saccharomyces cerevisiae cell.

Pseudomycelium

Candida albicans. Candida albicans. AA : Budding yeasts and pseudohyphae : Budding yeasts and pseudohyphae in tissue or exudate. in tissue or exudate. BB : Pseudohyphae and : Pseudohyphae and

chlamydospores in culture at 20chlamydospores in culture at 20C. C. CC : Germ tubes at : Germ tubes at 3737C.C.

Several important fungi are Several important fungi are thermally thermally DIMORPHICDIMORPHIC; ie, they ; ie, they form different structures at different form different structures at different temperatures. temperatures.

Dimorphic fungi exist as Dimorphic fungi exist as moldsmolds in in the saprophytic, free-living state at the saprophytic, free-living state at ambient temperature ambient temperature and as and as yeastsyeasts in host tissues at in host tissues at body body temperaturetemperature..

Cultures at different temperatureCultures at different temperature

Most fungi are Most fungi are obligate aerobesobligate aerobes, , some are some are facultative anaerobesfacultative anaerobes; ; but but nonenone are obligate anaerobes. are obligate anaerobes.

Some fungi reproduce sexually by Some fungi reproduce sexually by mating and forming mating and forming sexual sporessexual spores, , eg, eg, zygosporeszygospores, , ascosporesascospores, and , and basidiosporesbasidiospores. .

ZygosporesZygospores are single large spores are single large spores with thick walls with thick walls

AscosporesAscospores are formed in a sac are formed in a sac called ascuscalled ascus

BasidiosporesBasidiospores are formed externally are formed externally on the tip of a pedestal called a on the tip of a pedestal called a basidium. basidium.

The classification of these fungi is The classification of these fungi is based on their based on their sexual sporessexual spores. .

Most fungi of medical interest Most fungi of medical interest propagate propagate asexually asexually by forming by forming conidia conidia ((asexual sporesasexual spores) from the sides or ends ) from the sides or ends of specialized structures of specialized structures

The The shape, colorshape, color, and , and arrangementarrangement of of conidiaconidia aid in the identification of fungi. aid in the identification of fungi.

Some important conidia are Some important conidia are ( l ) arthrospores( l ) arthrospores** (2) chlamydospores (2) chlamydospores (3) blastospores (4) sporangiospores (3) blastospores (4) sporangiospores * The term “spores” can be replaced by “conidia”* The term “spores” can be replaced by “conidia”

PATHOGENESISPATHOGENESIS

The response to infection with many The response to infection with many fungi is the formation of fungi is the formation of GRANULOMASGRANULOMAS. .

Granulomas are produced in the major Granulomas are produced in the major systemic fungal diseases, eg, systemic fungal diseases, eg, coccidioidomycosis, histoplasmosis, and coccidioidomycosis, histoplasmosis, and blastomycosis, a s well as several others. blastomycosis, a s well as several others.

The cell-mediated immune response is The cell-mediated immune response is involved in granuloma formation. involved in granuloma formation.

Acute suppuration, characterized by Acute suppuration, characterized by the presence of neutrophils in the the presence of neutrophils in the exudate, also occurs in certain exudate, also occurs in certain fungal diseases such as aspergillosis fungal diseases such as aspergillosis and sporotrichosis. and sporotrichosis.

Fungi Fungi do notdo not have endotoxin in their have endotoxin in their cell walls and cell walls and do notdo not produce produce bacterial-type exotoxins.bacterial-type exotoxins.

In addition to mycotic infections, In addition to mycotic infections, there are 2 other kinds of fungal there are 2 other kinds of fungal disease : disease :

(1)(1) MYCOTOXICOSESMYCOTOXICOSES, caused by , caused by ingested toxins, andingested toxins, and

(2)(2) ALLERGIES ALLERGIES to fungal spores. to fungal spores.

LABORATORY LABORATORY DIAGNOSISDIAGNOSIS

There are 3 approaches to the There are 3 approaches to the laboratory diagnosis of fungal laboratory diagnosis of fungal diseases : diseases :

(1)(1) Direct microscopic examination Direct microscopic examination

(2)(2) Culture of the organism Culture of the organism

(3)(3) Serologic testsSerologic tests

Direct microscopic examination of Direct microscopic examination of clinical specimens such as sputum, lung clinical specimens such as sputum, lung biopsy material, and skin scrapings biopsy material, and skin scrapings depends on finding characteristic depends on finding characteristic asexual sporesasexual spores, , hyphaehyphae, or , or yeastsyeasts in in the light microscope. the light microscope.

The specimen is either treated with The specimen is either treated with 10% KOH10% KOH to dissolve tissue material, to dissolve tissue material, leaving the alkali-resistant fungi intact, leaving the alkali-resistant fungi intact, or stained with special fungal stains. or stained with special fungal stains.

Fungi are frequently cultured on Fungi are frequently cultured on Sabouraud's agarSabouraud's agar, which facilitates , which facilitates the appearance of the slow growing the appearance of the slow growing fungi by inhibiting the growth of fungi by inhibiting the growth of bacteria in the specimen. bacteria in the specimen.

Inhibition of bacterial growth is due to Inhibition of bacterial growth is due to the low pH of the medium and to the the low pH of the medium and to the chloramphenicol and cycloheximide chloramphenicol and cycloheximide that are frequently added. that are frequently added.

Tests for the presence of antibodies Tests for the presence of antibodies in the patient's serum or spinal fluid in the patient's serum or spinal fluid are useful in diagnosing the systemic are useful in diagnosing the systemic mycoses but less so in diagnosing mycoses but less so in diagnosing other fungal infections. other fungal infections.

As is the case for bacterial and viral As is the case for bacterial and viral serologic testing, a significant rise in serologic testing, a significant rise in the antibody titer must be observed the antibody titer must be observed to confirm a diagnosis. to confirm a diagnosis.

TREATMENTTREATMENT AMPHOTERICIN B & NYSTATINAMPHOTERICIN B & NYSTATIN Amphotericin BAmphotericin B, the most important antifungal , the most important antifungal

drug, is used in the treatment of a variety of drug, is used in the treatment of a variety of disseminated fungal diseases. It disrupts the cell disseminated fungal diseases. It disrupts the cell membrane of fungi owing to its affinity for membrane of fungi owing to its affinity for ergosterol, a component of fungal membranes ergosterol, a component of fungal membranes but not of bacterial or human cell membranes. but not of bacterial or human cell membranes. Amphotericin B has significant renal toxicity; Amphotericin B has significant renal toxicity; serum creatinine is used to monitor the dose.serum creatinine is used to monitor the dose.

Nystatin Nystatin is another polyene antifungal agent, is another polyene antifungal agent, which, because of its toxicity, is used topically which, because of its toxicity, is used topically for infections caused by the yeast for infections caused by the yeast CandidaCandida..

IMIDAZOLE IMIDAZOLE KetoconazoleKetoconazole is the most important of a is the most important of a

family of imidazole compounds with antifungal family of imidazole compounds with antifungal activity. They all inhibit ergosterol synthesis. activity. They all inhibit ergosterol synthesis. It is useful in the treatment of blastomycosis, It is useful in the treatment of blastomycosis, chronic mucocutaneous candidiasis, chronic mucocutaneous candidiasis, coccidioidomycosis, and skin infections caused coccidioidomycosis, and skin infections caused by dermatophytes.by dermatophytes. Fluconazole Fluconazole is useful in is useful in the treatment of candidal and cryptococcal the treatment of candidal and cryptococcal infections. infections. ItraconazoleItraconazole is used to treat is used to treat histoplasmosis and blastomycosis. histoplasmosis and blastomycosis. Miconazole Miconazole and and ClotrimazoleClotrimazole, 2 other , 2 other imidazoles, are useful for topical therapy of imidazoles, are useful for topical therapy of CandidaCandida infections and dermatophytoses. infections and dermatophytoses.