Tuesday, 9 July 2013

Microbiology II ; DOMAIN EUKARYA, Fungi

A. Fungi.
 There are more than 50,000 species of fungi; however, only a few hundred have been implicated in human disease and most human mycotic infections can be attributed to a few dozen species.

1. Taxonomy and nomenclature. In addition to their vegetative growth as yeasts or molds, fungi can produce spores via asexual or sexual reproduction. The classification of fungi is based on the mechanism of production and morphology of spores that result from sexual reproduction. Fungi are named using the Linnaean or binomial system as a genus and species (e.g., Homo sapiens is the genus and species for humans).

2. Structure. Fungi are eukaryotic organisms that grow in two basic forms. Molds grow by forming branching tubules called hyphae or mycelia (multiple hyphae). Yeasts are unicellular fungi and typically reproduce by budding, although some species produce pseudohyphae (chains of yeast cells). Most fungi are either yeasts or molds, although some can assume either morphology (dimorphic fungi). There are a number of structural features of fungal cells that are noteworthy, particularly with respect to targeted antifungal therapy.

a. The fungal cell wall is composed primarily of chitin, as opposed to bacterial cell walls, which are composed of peptidoglycan; thus, fungi are not sensitive to antimicrobials such as penicillin, which interfere with peptidoglycan synthesis.

b. The predominant sterol in the fungal cell membrane is ergosterol, whereas human cell membranes contain cholesterol. Several antifungal agents target this difference between fungal and human cell structure.

3. Fungal physiology. Most fungi are obligate aerobes, although some are facultative anaerobes (that makes ATP by aerobic respiration if oxygen is present but is also capable of switching to fermentation).
None are obligate anaerobes. 
Fungi are dependent on a preformed organic source of carbon. i.e can not make Photosynthesis

4. Pathogenicity. Healthy immunocompetent individuals have a high level of innate resistance to fungal infections.
a. Primary pathogens are fungi that can infect normal, immunocompetent hosts (e.g., Blastomyces dermatitidis, Histoplasma capsulatum, Coccidioides immitis). All of the primary systemic fungal infections are respiratory infections.
b. Opportunistic fungi are fungi that typically infect patients with impaired defenses. When normal host defenses are compromised, the host is more susceptible to certain fungal infections. Most fungal infections are opportunistic infections.

5. Mechanisms of pathogenicity and important immune defenses for selected fungal diseases.
a. Cutaneous mycoses. Dermatophytoses are diseases caused by a group of related fungi in the genera Trichophyton, Epidermophyton, and Microsporum. These fungi are able to invade
the skin, hair, and nails, owing in part to their ability to break down keratin. Penetration below the epidermis is rare. Various forms of dermatophytoses are referred to as ringworm or “tineas,” being further defined by the affected anatomical site (e.g., tinea corporis of the body, tinea cruris of the groin, tinea pedis of the foot, tinea unguium of the nails, and tinea capitis of the scalp). Intact epithelium including chemical and bacterial factors (normal flora and bacterial metabolites) are important for inhibiting or preventing fungal growth (e.g., tinea pedis [athlete’s foot] is often associated with damaged skin areas, moisture, specific skin chemistry, or heavy exposure to the fungi).

b. Systemic mycoses due to dimorphic fungi. These primary systemic pathogens exist as a mold form in nature and as a yeast in infections. They are inhaled into the lungs from an environmental source and then disseminate to involve other tissues. Reduced cell-mediated immunity predisposes individuals to disseminated disease with Histoplasma and Coccidioides.

c. Candida species, most commonly Candida albicans, are opportunistic fungal pathogens that can cause infections in virtually any organ system under the right circumstances. Candida are part of the normal flora of the gastrointestinal tract of many healthy individuals; therefore, the predominant source for infection is opportunistic spread of endogenous organisms (e.g., urinary tract infection of indwelling urinary catheter, pneumonia following aspiration, endocarditis of prosthetic heart valves, hematogenous infection following immunosuppression, Candida vulvovaginititis following antibiotic therapy).

d. Aspergillus is a group of environmental fungi that can colonize the sinuses and upper respiratory tract following environmental exposure. A reduced number of neutrophils predispose patients to disseminated infections caused by Aspergillus. Inhalation of environmental Aspergillus can also lead to hypersensitivity reactions (e.g., allergic bronchopulmonary aspergillosis).

e. A number of fungi produce powerful toxins. The aflatoxins are coumarin derivatives produced by Aspergillus flavus.

6. Antifungal therapy (will be discussed further later).
a. Azole drugs (itraconazole, fluconazole, and ketoconazole) inhibit the synthesis of ergosterol, which is a structural part of the fungal cell membrane.
b. Polyene antifungals, such as amphotericin B, associate preferentially with ergosterol in the fungal cell membrane and disrupt the cell membrane integrity. It is typically used for systemic mycoses, and resistance is rare. Nystatin is structurally related to amphotericin B although nystatin can only be used as a topical or oral suspension.
c. Echinocandins, such as caspofungin (Cancidas), anidulafungin (Eraxis), and micafungin (Mycamine), interfere with the synthesis of the fungal cell wall by inhibiting the 1,3-bglucan synthase.

Comprehensive Pharmacy Review
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