Candida albicans

Figure 1. Skin Smear Candida albicanswww.meddean.luc.edu

Contents

1. Introduction to Mycology

2. Biological Profile

3. Disease capabilities

4. Pathogenesis

5. Detection

6. Drug therapy

7. Research

The SituationFrequency

- 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

www.ken.coar.org

www.arboretum.harvard.edu

www.bio.umass.edu

Mycology BasicsKingdom: Fungi

More than 10 million species, but only ~400 human disease (*)

Sexual GroupsAscomycota*Basidiomycota*Zygomycota*ChytridiaFungi Imperfecti*

Very few species are in a commensal relationship with humans- includes Candida albicans and Malasezia furfur

Diseases caused by fungi are usually accidentalEndogenous and Exogenous SourcesIncreasing problem due to antibacterial & immunosuppressive agentsMolecular mechanisms of pathogenesis not well-defined

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 structuresplaces them in the appropriate category. (Baron, 1996)

Figure 1. Penicillium chrysogenum www.doctorfungus.org

Fungal Characteristics

Plant-like lacking chlorophyll

Cell wall chitinous matrix

Free-living saprobes and heterotrophsneeds Carbon source and Nitrogen source

Yeasts or Molds or both

Success of an infectionAccidentalOvercoming host barriersPresiding in host with immunological defects

Figure 1. Typical Yeast Figure 2. Typical mould

Yeast Characteristics

solitary, unicellular

reproduction via budding

rounded shape

moist & mucoid colonies

Mould Characteristics

filamentous hyphae

hyphal formation

tips may be rounded(conidia/spores)

Yeast Bud Formation

Figure 1. Stages of bud growth andyeast cell cycle (Baron et. Al., 1996)

Hyphal Formation

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

Biology of Candida albicansCommensal Pathogen

A thin-walled dimorphic fungus

MorphogenesisUnicellular yeast (harmeless)Filamentous (pathogenic)

Principal Cell Wall PolymersGluccanMannan

Strict aerobe, favors moist surfacesCommensally found in gut, genitals, and lungsBody Temp 37º C, neutral pH

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

Rapid Multiplication & Spread

Diseases by C. albicans

Thrush

Esophagitis

Cutaneous Candidiasis

Genital Yeast Infections

Deep Candidiasis

Figure 1. Angular chelitis (www.emed.com)

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

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

Oropharyngeal Thrush

* Pseudomembranous

* Atrophic

* Angular chelitis

Symptoms

Risk FactorsHIV

Treatment: topical antifungals

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)

Deep Candidiasis

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

PathogenesisHost Recognition

Adhesins

EnzymesHydrolases: Phosphoplipases, Lipases, Proteinases

MorphogenesisYeast form to Filamentous hyphae/pseudohyphae

Phenotypic Switching

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.

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

(Fraunhofer, 2002)

MORPHOGENESIS

Figure 2. Morphogenic forms of Candida albicanshttp://cbr-rbc.nrc-cnrc.gc.ca/thomaslab/candida/caindex.html

Figure 1. Morphogenesis.Morphogenesis in C. albicans is a pivotal virulence factor that allowsrapid multiplication andsubsequent disseminationin host tissue.(www.kent.ac.uk)

Tools for Detection & Diagnosis

PCR Based Molecular Techniques

targets SAPs

Advantages

Disadvantages

Future

Non-PCR Based

Fluorescent in situ hybridization

Old MethodsRestriction Enzyme Analysis

Current methodsCulture and Serology

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Fig. 1. Throat Swab (www.nlm.nih.gov)

Current Drug Therapies

FDA approved antifungal drugsAmphotericin B (Fungizone)Clotrimazole (Mycelex)Fluconazole (Diflucan)Itraconazole (Sporanox)Ketoconazole (Nizoral)Nystatin (Mycostatin)

Medical Economics. Drug Topics Red Book. Montvale, NJ: Medical EconomicsCo., Inc., 2000.

Major Drug CategoriesPolyenes

Problems: Azoles

Problems: Enhanced drug efflux

Catalase activity, ergosterol production

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

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

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A. http://www.intelihealth.com/IH/ihtIH/WSIHW000/9339/31092.html

B. http://www.emedicine.com/emerg/topic76.htm

C. http://www.ncbi.nlm.nih.gov

D. www.webpathology.com

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