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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)
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)
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
QuickTime™ and aTIFF (Uncompressed) decompressorare needed to see this picture.
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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