Candida albicans

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

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

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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 gt 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
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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
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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)
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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
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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
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Yeast Bud Formation
Figure 1. Stages of bud growth and yeast cell
cycle (Baron et. Al., 1996)
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Hyphal Formation
Figure 1. Polarized hyphal formation (Baron et.
Al., 1996)
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Biology of Candida albicans
Commensal
Pathogen
A thin-walled dimorphic fungus Morphogenesis Uni
cellular 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
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Diseases by C. albicans

• Thrush
• Esophagitis
• Cutaneous Candidiasis
• Genital Yeast Infections
• Deep Candidiasis

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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)
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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.u
k)
Figure 2. Plasma cell balanitis. A band-like
infiltrate of plasma cells is in the dermis of
the male penis. (www.webpathology.com)
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Deep Candidiasis
Figure 1. Four forms of invasive candidiasis
(www.doctorfungus.org)
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Pathogenesis
Host Recognition Adhesins Enzymes Hydrolases
Phosphoplipases, Lipases, Proteinases Morphogenes
is Yeast form to Filamentous hyphae/pseudohyphae
Phenotypic Switching
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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)
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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/c
andida/caindex.html
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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
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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)
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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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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.