Candida albicans

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

2. Contents • Introduction to Mycology • Biological Profile • Disease capabilities • Pathogenesis • Detection • Drug therapy • Research

3. 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

4. Mycology Basics Kingdom: Fungi More than 10 million species, but only ~400 human disease (*) Sexual Groups Ascomycota* Basidiomycota* Zygomycota* Chytridia Fungi Imperfecti* Very few species are in a commensal relationship with humans - includes Candida albicans and Malasezia furfur Diseases caused by fungi are usually accidental Endogenous and Exogenous Sources Increasing problem due to antibacterial & immunosuppressive agents Molecular mechanisms of pathogenesis not well-defined www.ken.coar.org www.arboretum.harvard.edu www.bio.umass.edu

5. The 5 main groups Figure 1. Classification of Fungi. Fungi are classified based on their ability to reproduce sexually, asexually, by a combination of both. The different reproductive structures places them in the appropriate category. (Baron, 1996)

6. Fungal Characteristics Plant-like lacking chlorophyll Cell wall chitinous matrix Free-living saprobes and heterotrophs needs Carbon source and Nitrogen source Yeasts or Molds or both Success of an infection Accidental Overcoming host barriers Presiding in host with immunological defects Figure 1. Penicillium chrysogenum www.doctorfungus.org

7. Yeast Characteristics solitary, unicellular reproduction via budding rounded shape moist & mucoid colonies Mould Characteristics filamentous hyphae hyphal formation tips may be rounded (conidia/spores) Figure 1. Typical Yeast Figure 2. Typical mould

8. Yeast Bud Formation Figure 1. Stages of bud growth and yeast cell cycle (Baron et. Al., 1996)

9. Hyphal Formation Figure 1. Polarized hyphal formation (Baron et. Al., 1996)

10. Biology of Candida albicans Commensal Pathogen A thin-walled dimorphic fungus Morphogenesis Unicellular yeast (harmeless) Filamentous (pathogenic) Principal Cell Wall Polymers Gluccan Mannan Strict aerobe, favors moist surfaces Commensally found in gut, genitals, and lungs Body Temp 37º C, neutral pH Figure 1. Yeast in Oral Scraping A sample of an oral scraping contains yeast cells and pseudohyphae (www.doctorfungus.org) Rapid Multiplication & Spread

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

12. Oropharyngeal Thrush * Pseudomembranous * Atrophic * Angular chelitis Symptoms Risk Factors HIV Treatment: topical antifungals Figure 1. Angular chelitis (www.emed.com) Figure 3. Oral Thrush, pseudomembranous (www.emed.com) Figure 2. Oral Thrush, atrophic (www.mycolog.com)

13. Genital Yeast Candidiasis Symptoms Risk Factors - disruption of normal microbiota Treatment - direct genital administration - tablets, suppositories, creams Figure 1. Vaginal Yeast Culture (www.euromeds.co.uk) Figure 2. Plasma cell balanitis. A band-like infiltrate of plasma cells is in the dermis of the male penis. (www.webpathology.com)

14. Deep Candidiasis Figure 1. Four forms of invasive candidiasis (www.doctorfungus.org)

15. Pathogenesis Host Recognition Adhesins Enzymes Hydrolases: Phosphoplipases, Lipases, Proteinases Morphogenesis Yeast form to Filamentous hyphae/pseudohyphae Phenotypic Switching

16. 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)

17. 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

18. Tools for Detection & Diagnosis Old Methods Restriction Enzyme Analysis Current methods Culture and Serology PCR Based Molecular Techniques targets SAPs Advantages Disadvantages Future Fig. 1. Throat Swab (www.nlm.nih.gov) Non-PCR Based Fluorescent in situ hybridization

19. Current Drug Therapies Major Drug Categories Polyenes Problems: Azoles Problems: Enhanced drug efflux Catalase activity, ergosterol production FDA approved antifungal drugs Amphotericin B (Fungizone) Clotrimazole (Mycelex) Fluconazole (Diflucan) Itraconazole (Sporanox) Ketoconazole (Nizoral) Nystatin (Mycostatin) Fig. 1. Fungizone (www.bms.se)

20. 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

21. References 23. Burnie J. & R. Matthews. 2003. The role of antibodies against hsp90 in the treatment of fungal infections Drug News Perspect 16(4): 205-210.