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Figure 1. Skin Smear Candida albicans www.meddean.luc.

edu

Candida albicans

Contents
1. 2. 3. 4. 5. 6. 7. Introduction to Mycology Biological Profile Disease capabilities Pathogenesis Detection Drug therapy Research

The Situation
Frequency
- most common fungal pathogen worldwide - 4th leading causes of nosocomial infections, 40% mortality - significant mortality and morbidity in low birth-weight infants - affects 75% women, 45% experience recurrenceA > 10 million visits/year - classified as a STD by CDC

Immunocompromised - cancer and HIV-AIDs patientsC


- most commonly manifested in patients with leukemia or HIV-AIDs infections. Oral candidiasis is often a clue to acute primary infectionC

Public Concerns - increasing resistance to drug therapies due to antibiotics and


antifungals

Biology of Candida albicans


Commensal Pathogen

A thin-walled dimorphic fungus


Morphogenesis Unicellular yeast (harmeless) Filamentous (pathogenic) Principal Cell Wall Polymers Gluccan Mannan

Figure 1. Yeast in Oral Scraping A sample of an oral scraping contains yeast cells and pseudohyphae (www.doctorfungus.org)

Strict aerobe, favors moist surfaces Commensally found in gut, genitals, and lungs Body Temp 37 C, neutral pH

Rapid Multiplication & Spread

Diseases by C. albicans
Thrush Esophagitis Cutaneous Candidiasis Genital Yeast Infections Deep Candidiasis

Oropharyngeal Thrush
* Pseudomembranous * Atrophic * Angular chelitis Symptoms Risk Factors HIV
Figure 1. Angular chelitis (www.emed.com)

Treatment: topical antifungals

Figure 2. Oral Thrush, atrophic (www.mycolog.com)

Figure 3. Oral Thrush, pseudomembranous (www.emed.com)

Genital Yeast Candidiasis


Symptoms Risk Factors - disruption of normal microbiota
Figure 1. Vaginal Yeast Culture (www.euromeds.co.uk)

Treatment - direct genital administration - tablets, suppositories, creams


Figure 2. Plasma cell balanitis. A band-like infiltrate of plasma cells is in the dermis of the male penis. (www.webpathology.com)

Deep Candidiasis

Figure 1. Four forms of invasive candidiasis


(www.doctorfungus.org)

Pathogenesis
Host Recognition Adhesins Enzymes Hydrolases: Phosphoplipases, Lipases, Proteinases

Morphogenesis Yeast form to Filamentous hyphae/pseudohyphae Phenotypic Switching

Virulence assay of different C. albicans strains using the skin equivalent (AST 2000)
Figure 1. skin equivalent before infection

Figure 2. Infection with pathogenic clinical isolate of C. albicans. After 48 h the yeast penetrates the skin equivalent and destroys the tissue

Figure 3. Infection with non-pathogenic C. albicans. This strain is not able to penetrate into the tissue and thus behaves as avirulent as shown in the mouse model of systemic infection.

(Fraunhofer, 2002)

MORPHOGENESIS

Figure 1. Morphogenesis. Morphogenesis in C. albicans is a pivotal virulence factor that allows rapid multiplication and subsequent dissemination in host tissue. (www.kent.ac.uk)

Figure 2. Morphogenic forms of Candida albicans


http://cbr-rbc.nrc-cnrc.gc.ca/thomaslab/candida/caindex.html

Tools for Detection & Diagnosis


Old Methods Restriction Enzyme Analysis

Current methods Culture and Serology


PCR Based Molecular Techniques
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targets SAPs
Advantages Disadvantages Future Non-PCR Based Fluorescent in situ hybridization
Fig. 1. Throat Swab (www.nlm.nih.gov)

Current Drug Therapies


Major Drug Categories Polyenes Problems: Catalase activity, ergosterol production Azoles Problems: Enhanced drug efflux

FDA approved antifungal drugs


Amphotericin B (Fungizone) Clotrimazole (Mycelex) Fluconazole (Diflucan) Itraconazole (Sporanox) Ketoconazole (Nizoral) Nystatin (Mycostatin)

Qu i ckTi me an d a TIFF (Un co mp re s se d) de co mp re s so r a re ne ed ed to se e thi s p i ctu re .

Fig. 1. Fungizone (www.bms.se)

Medical Economics. Drug Topics Red Book. Montvale, NJ: Medical Economi cs Co., Inc., 2000.

Research
Biotechnological methods for rapid identification and detection of Candida strains New antifungal agents Molecular pathogenesis

Emerging opportunistic strains


Public Health Measures in limiting nosocomial-related infections

References
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